Untitled - Instituto de Química Física Rocasolano

Transcripción

Scientific Report 2013-2014
Physical Chemistry Institute
Rocasolano
Spanish National Research Council
Editors:
Clara Gómez, José M. Pérez Cañadillas and Lourdes Infantes
Composition and layout:
José Luis Rojo Marco, Producción Gráfica Multimedia PGM
The editors would like to thank all the staff of the Institute who have contributed
to the realization of this Scientific Report.
Table of Contents
Direction. Presentation
3
Department of Crystallography
and Structural Biology 7
Department of Structure,
Energy and Chemical Reactivity
30
Department of Biological
Physical Chemistry
61
Department of Low
Dimensional Systems,
Surfaces and Condensed
Matter
115
Research Support
Services
153
ANNEX 1.
Singular Instrumentation
174
ANNEX 2.
IQFR Facts and Figures
181
Juan de la Figuera Bayón Director Douglas Vinson Laurents
Scientist vice-director
Juan Zenón Dávalos Prado
Technical vice-director
Presentation
The “Rocasolano” Institute of Physical Chemistry
(IQFR) continues the scientific tradition of the
National Institute of Physics and Chemistry,
whose building it still occupies. The original
Institute, which was part of the Board of
Extension of Studies and Scientific Research
(JAE), was opened in 1932, thanks to a generous
grant from the Rockefeller Foundation. This
donation was made on the condition that the
building be exclusively dedicated to research,
after the Rockerfeller Foundation had detected
a group of competent scientists doing their
work in precarious conditions. It was the first
modern research center in Spain both in terms
of the building design and its operating rules
which were comparable to the best modern day
centers. Let us note, for example, the criteria
for the forming a new section: “A new section
will not created until a qualified person is
identified who is recognized as an authority in
his/her research field”. This Institute’s first years
witnessed the advances made by Blas Cabrera,
Miguel Catala, Enrique Moles and Julio Palacios,
and the level of its international connections is
illustrated by renowned visitors such as Arnold
Sommerfeld, William Bragg or Marie Curie. This
glorious period was cut short by the Spanish
Civil War.
Juan de la Figuera Bayón
the Institute focuses its research in various fields
of Physical Chemistry, emphasizing its strong
multidisciplinary nature at the border between
Chemistry, Physics, Biology and Materials
Science. It is known for its set of advanced
techniques that enhance the capabilities of the
center and permit our research to span many
different fields. In this era of overly specialized
institutes, the IQFR is one of the few institutes
which maintain a generalist nature that can
incorporate new research fields that share
the physicochemical methodologies, among
which we highlight Atmospheric Chemistry or
Biological Chemistry. In the first case, the recent
addition of a dedicated Atmospheric Chemistry
group benefits from the previous experience of
other groups in photolysis, chemical reactivity
and surface reactivity. In the second case, the
application of chemical and physical techniques
to solve problems of biological interest has
developed considerably. We take advantage our
own unique instrumentation such as the High
Field Nuclear Magnetic Resonance Laboratory,
home to the CSIC’s highest field nuclear magnetic
resonance spectrometer (one of only three
in Spain of its kind), fluorescence techniques,
high resolution mass spectrometry and the
Laboratory for X-ray diffraction of proteins.
The experience of researchers in using unique
instrumentation has made them frequent users
of the ALBA synchrotron in Barcelona.
Later, in 1946, the Spanish National Scientific
Research Council (CSIC), which inherited the
tasks and responsibilities of the JAE, created
the “Rocasolano” Institute of Physical Chemistry
(IQFR). Antonio Rius was the first director. Since
then, the IQFR has been a national reference in
research in Pure and Applied Physical Chemistry.
Its generalist vocation is evidenced by the
fact that for decades it spawned many more
specialized research institutes within the CSIC
as well as a number of university departments
throughout Spain.
Since the days of the National Institute of Physics
and Chemistry, the research has evolved and
changed. Some lines of research have become
extinct or are continued in other centers which
originated from the IQFR. Other lines have
become international benchmarks. At present,
In short, the IQFR covers topics related to
Scientific Report 2013/2014
3
burden on the Institute’s work. The IQFR, due to
the fundamental nature of much of its research,
has been funded mainly by competitive projects
in local, national and international calls. The
erratic national policy with unpredictable
timing of the calls and sharp cuts in past years
has been a major problem. Although IQFR
has maintained the highest levels of scientific
productivity in its history, the uncertainty and
the feeling of a lack of support for research has
led two excellent research groups to move out
of the CSIC and Spain, respectively. Moreover,
the staff has suffered from the retirements of
scientific and technical personnel, the absence
of new positions and the drastic decrease in our
ability to hire trainees. As for the equipment,
the Institute has worked hard in an emergency
mode to keep the equipment in operation; in
the case of the High Field Nuclear Magnetic
Resonance Laboratory, the Institute received
vital support from the CSIC.
fundamental Physical Chemistry, the study of
energy and chemical reactivity (Ion-Molecule
Reactions, Thermochemistry, Computational
Chemistry, Reactions at Surfaces), which
complement the interdisciplinary research
in Science and Technology of Materials and
Nanotechnology, the study of the molecular
basis of biological function in systems with
increasing levels of organization, and the impact
of chemical processes on Climate Change and
pollution.
The Institute has specialized support units in
electronics, mechanics and glass blowing, which
are vital to much of the experimental work
carried out in the IQFR. The same is true of the
Stockroom and also the Library, which is a direct
descendant of the original library of the National
Institute of Physics and Chemistry. It is the best
Chemistry and Physics library in Spain and one
of the top scientific libraries in Europe with an
impressive subscription to hundreds of journals
and an important historical collection. In the
current digital age, our Library is a major source
for loans to other institutions.
Despite these difficulties the Institute maintains
an excellent research level and outstanding
technical ability. It is thus positioned to take
advantage of any improvement in the research
climate in Spain and to contribute to the
development of Physical Chemistry in its many
facets.
However during 2013 and 2014, the economic
crisis and the management of its impact on
research and development in Spain, and more
specifically in the CSIC, have been a significant
4
Departments
and Structural Biology
Armando Albert
Department of Structure, Energy
and Chemical Reactivity
Rafael Notario
• Energetics, Structure and Molecular Interactions Group
• Photolysis and Chromatography Group
• Atmospheric Chemistry and Climate Group
Department of Biological Physical Chemistry
Marta Bruix
• NMR of Protein Structure, Dynamics and Interactions
Group
• Protein Bioconformatics and Assamblies Group
• Structural Bioinformatics Group
• Fluorescence and Molecular Biophysics Group
• Protein Structure and Thermodynamics Group
• NMR of Nucleic Acids Group
Department of Low Dimensional
Systems, Surfaces and Condensed Matter
José F. Marco
• Lasers, Nanostructures and Materials Processing Group
• Laser Materials and Laser-Materials Interaction Group
• Statistical Mechanics and Condensed Matter Group
• Surface Analysis and Mössbauer Spectroscopy Group
5
Introduction
The members of the Department constitute
the Group of Protein Crystallography
and Molecular Recognition in Biological
Processes and focus their research to
understand the biological functions of
macromolecules in terms of their 3D structure
at atomic, molecular and supramolecular
levels. This provides information on their
functionality and ability to recognize
other molecular partners or a substrate,
or to develop their activity in a particular
environment. To achieve these objectives,
we combine chemical, physical-chemical
and biological approaches. Among them,
crystallography occupies a preferential place
since it is the most powerful technique to
characterize single proteins or large stable
macromolecular complexes at atomic level.
Such knowledge provides the basis for new
medical treatments and many biotechnological
applications. In addition, our Department is
also involved in the development of novel and
efficient methods and strategies for phasing
structures that make possible the solution of
protein structures.
The Department is equipped with the state
of the art technologies to develop our
research. Our molecular biology laboratory
is perfectly set up and equipped with all the
modern technologies to produce recombinant
proteins at milligram scale. The diffraction
laboratory includes a new rotating anode
generator equipped with two area detectors
and a micro source generator for testing
crystals. We also provide X-ray facilities for
the crystallographic community through the
RedLab network, which coordinates all the
technological platforms of the Madrid Regional
Government. In addition, we have established
an automated crystallization platform which
offers the newest and fastest tools for the
screening of crystallization conditions using
a minimum amount of protein sample. The
platform includes two crystallization robots
and a “crystal farm” for storage and analysis
of the experiments. All these facilities are
available for all CSIC researchers and for
those coming from other institutions.
Scientific Report 2013/2014 Department of Crystallography
8
Group of Protein Crystallography and Molecular
Recognition in Biological Processes
Tenured Staff Scientists
Armando Albert de la Cruz
(Associate Professor) ReID ORCID SCOPUS
Beatriz González Pérez
(Assistant Professor) ReID ORCID SCOPUS
Juan Antonio Hermoso Domínguez
(Professor) ReID
Yanaisis Álvarez Sánchez
(Fellowship, until 15/01/2014)
Cecilia Artola Recolons
Jose Ignacio Baños Sanz
Noelia Bernardo García (Contract)
Lourdes Infantes San Mateo
Alejandra Carriles Linares
(Contract, from 09/09/2014)
José Miguel Mancheño Gómez
Antonio Chaves Sanjuán
Martin Martínez Ripoll
(Professor) ReID ORCID
Teresa Domínguez Gil-Velasco (Fellowship)
Elsa Franco Echevarría
María José Sánchez-Barrena
(Ramón y Cajal) ReID SCOPUS
Julia Sanz Aparicio
Non-tenured Scientists
Sergio Galán Bartual (Juan de la Cierva)
Iván Acebrón Avalos
Javier Gutierrez Fernandez (Contract)
Mercedes Ramírez Escudero (Contract)
María Ángela Sainz Polo (Fellowship)
Technical Staff
Juana María González Rubio
Ainhoa Erce Llamazares
(Contract, until 01/07/2014)
Rocío Benavente Rubio
Lisandro Otero
Mª Mar Esteban-Torres
(Contract, 21/04/2014-20/06/2014
Doctoral Students
Ivan Acebrón Avalos (Fellowship, until 31/7/2013)
Alzoray Rojas Altube
9
Strategic Aims
•
Characterization of the mechanisms of bacterial infection and the development of new
therapeutic tools against multiresistant pathogens.
- Structural and functional characterization of pivotal proteins involved in bacterial virulence.
- To assess the role of pneumococcal surface-exposed proteins in pathogen-host interactions.
- To identify the molecular basis of bacterial cell wall remodeling and its implications in
antibiotics resistance.
- To develop new lead compounds and enzybiotics against bacterial infections.
•
Molecular basis of substrate recognition and structure-based design of enzymes for
biotechnology.
- Unravel the molecular mechanisms involved in biologically relevant carbohydrates
recognition and processing.
- Enzymatic degradation of plant cell-walls.
- Structure-based design of enzymes:
glycosilation of bioactive products.
production of prebiotic oligosaccharides and
- Structural enzymology of lipases and esterases from the lactic acid bacterium Lactobacillus
plantarum.
- Structural basis of the specificity of fungal lectins: applications of β-trefoil lectins as fusion
tags.
•
The structural analysis of the cell signaling components in mammals and plants. Signal
regulation through protein-protein interactions.
- Structural Biology of Inositide Signalling and Inositide regulation and synthesis. Design of
inhibitors of the pathway with application in cell biology and cancer biomedicine.
- Structure and inhibition of UDG, a protein invoved in DNA repair
- Structure and function of Frequenin: synaptic function control
- Structural basis of abiotic stress plant cell response: The auxin and abcisic mediated
pathway. The development mimicking compounds with biotechnological applications.
•
Education and public outreach activities
10
Results
Structural biology
pathogenesis
of
bacterial
wall mediated by non-canonical D-amino acids
(NCDAA).
Antimicrobial resistance is one of the most
serious health threats. Cell-wall remodeling
processes are tightly regulated to warrant
bacterial survival and most of them are directly
linked to antibiotic resistance. The main goal of
Hermoso’s team is to generate the knowledge,
based on an integrative study of some critical
bacterial cell wall remodeling processes, to
provide new pharmacological targets in the fight
against some of the most dangerous multidrugresistant pathogens. We focus on five main
general objectives: (i) the study of the virulence
mechanisms mediated by pneumococcal surface
proteins, (ii) the molecular characterization of the
pneumococcal divisome, (iii) Cell-wall recycling
and antibiotics resistance in G(-) pathogens,
(iv) The multidrug resistance mechanisms in
MRSA, (v) Synthesis and regulation of cell
Inside these objectives, some of the main
achievements during 2013-2014 were:
Antibiotics
pathogens
resistance
in
bacterial
We have discovered that resistance in Methicillinresistant S. aureus (MRSA) is related with the
existence of a distant allosteric site that regulates
activity of critical PBP2a enzyme (Otero et al.
2013; Fishovitz et al. 2014). We have also
recently used a combination of structural and
biophysical techniques to study the link between
some cell-wall recycling enzymes (AmpDh2,
AmpDh3 and MltC, Figure 1) and antibiotic
resistance in Gram(-) organisms (MartínezCaballero et al. 2013; Lee et al. 2013; ArtolaRecolons et al. 2014).
Figure 1: Three-dimensional structures of MltC, AmpDh2 and AmpdH3 involved in peptidoglycan
(black sticks) recycling and antibiotics resistance in G(-) pathogens.
11
Pneumococcal
virulence
surface-proteins
and
We characterized at physiological, functional
and structural levels two novel surface-exposed
thioredoxin-family lipoproteins, Etrx1 and Etrx2
(Saleh et al. 2013). The impact of both Etrx
proteins and their redox partner methionine
sulfoxide reductase MsrAB2 on pneumococcal
pathogenesis was assessed in mouse virulence
studies and phagocytosis assays. The results
demonstrate that loss of function of either
both Etrx proteins or MsrAB2 dramatically
attenuated pneumococcal virulence in the acute
mouse pneumonia model and that Etrx proteins
compensate each other. Our results describe
for the first time the complete extracellular
oxidative-stress resistance mechanism in S.
pneumoniae (Figure 2) (see movie in http://bit.
ly/1uOvIOB). Identification of this system and
its target proteins paves the way for the design
of novel antimicrobials.
The
Divisome
Pneumococcus
machinery
We have very recently provided the structural and
functional characterization of the essential PcsB
protein. Combined study by X-ray crystallography,
SAXS, Analytical ultracentrifugation and protein
engineering allowed us to propose a mechanism
of cell division mediated by PcsB (Bartual et al.
2014).
Figure 2: The complete extracellular oxidative-stress resistance system in Streptococcus
pneumoniae is composed by two integral membrane proteins (CcdA1 and CcdA2), two
thioredoxin-like lipoproteins (Etrx1 y Etrx2) and a methionine sulfoxide reductase (MsrAB2).
12
in
Structural
Basis
of
Endogenous
Polysaccharides
Receptor SIGN-R1
for
Recognition
and
Microbial
by
Macrophage
The classical pathway is one of the major
complement activation mechanisms and is
required for innate protection against pathogenic
microorganisms. SIGN-R1 receptor mediates a
novel complement activation strategy in splenic
marginal zone macrophages and prevents
encapsulated pathogens such as S. pneumoniae
from escaping C3 opsonization. Structural
determination SIGN-R1 revealed two binding
sites allowing SIGN-R1 to simultaneously bind
both immune glycoproteins and microbial
polysaccharide components, accommodating
SIGN-R1’s ability to relate the recognition
of microbes to the activation of the classical
complement pathway (Silva-Martín et al. 2014).
Inositol
phosphates:
regulation and function
synthesis,
Our group is focused on the structural biology
of enzymes involved in the Inositol phosphates
(IP) metabolism. IPs are small molecules that
present multiple functions in cells; they act as
second messengers or participate in crucial
events as DNA repair and edit, RNA export,
vesicle trafficking etc. Several proteins are able
to synthesize different IPs, and many others are
able to bind them to carry out their function. Our
last work has been focused on the activation of
an IP kinase (IP3 3K) by calmodulin. IP3 3K is
an essential enzyme that binds an IP (IP3) to
yield other IP (IP4). During the last decades,
plenty of work has been done on this enzyme
since its substrate (IP3) is a second messenger
involved in Ca2+ signalling and its product IP4
is necessary for lymphocyte development. In
turn, recent studies show a role for IP3 3K in
the metastatic potential of lung cancer cells. We
have recently determined the crystallographic
structures of a protein-protein complex between
calmodulin and the CAM binding domain present
in IP3 3K. This structure in combination with
SAXS data allowed us to propose a complete
structural model of IP3 3K-CAM complex (Figure
3). The results reveal essential features about
the mechanism of regulation of IP3 3K and a
novel example of how CAM recognise its targets.
In conclusion, the structure obtained represents
a key piece for the IP metabolism understanding
(Franco-Echevarria et al. 2014).
Figure 3. An experimental model for IP3 3-K (green and brown) regulation by calmodulin
(blue) obtained by combination of X-ray structures and SAXS data.
13
Inhibition of UDG, an
involved in DNA repair
enzyme
and a dimer of p56 at atomic resolution, as well
as the structure of UDG in free state.
In collaboration with Prof. Margarita Salas group
(CBM-CSIC) we have made the structural study
of Uracil DNA glycosilase (UDG enzyme). Uracil
DNA glycosylases (UDGs) are a family of key
enzymes that initiate the base scission repair
(BER) pathway detecting uracil and removing it
from DNA. Some viral bacteriophages encode
proteins that are able to inhibit this enzyme,
ensuring that way they genome is replicated in
host cells. P56 is one of those proteins, which
is encoded by f29, a Bacillus subtilis phage, and
inhibits UDG with high affinity. We have solved
the crystal structure of a complex between UDG
The complex structure has revealed that the
binding between both proteins is very specific,
presenting multiple polar and hydrophobic
interactions. This high specificity arises from
p56 ability to mimic UDG and DNA binding. On
one hand, both subunits of p56 grab the UDG
residue responsible of UDG insertion into the
DNA (Phe191). On the other hand, p56 blocks the
UDG active site impeding the uracil binding and
its cleavage. This work allowed us to understand
the structural bases of UDG inhibition and the
ability of p56 to mimic the DNA binding to UDG
(Baños-Sanz et al. 2013).
Figure 4. Structure of the complex between UDG (cream surface) and p56 (cartoon
representation, each p56 subunit shown in different colour).
14
Frequenin/NCS-1
as
a
pharmacological target for synapse
regulation
in
X-linked
mental
retardation and autism
The conserved Ca2+-binding protein Frequenin/
Neuronal Calcium Sensor 1 (Frq/NCS-1) is
involved in pathologies such as X-linked mental
retardation and autism, which result from
abnormal synapse number and probability of
neurotransmitter release per synapse. Both
synaptic features are likely co-regulated but
the intervening mechanisms remain poorly
understood. Thus, we have conducted a
multidisciplinar approach including biochemical,
crystallographic and cell biological studies to
shed light into this issue.
We found that Frq has to interacts with Ric8,
an activator of G protein complexes, to regulate
synapse number and neurotransmitter release.
To understand the structural determinants of
Frq-Ric8 binding, we have solved the structure
of dFrq2 and compared it with dFrq1, which
is 95% identical and does not bind Ric8. Site
directed mutagenesis on Frq1 followed by pulldown assays showed that the differential amino
acids R94 and T138 account for this specificity.
Human NCS-1 and Ric8a reproduce the binding
and maintain the structural requirements at
these key positions. These results expose the
Frq2-Ric8a interacting surface as a potential
pharmacological target for NCS-1 related
diseases and provide key data towards the
corresponding drug design (Baños-Mateos et
al. 2014 and Romero-Pozuelo et al. 2014). Our
on-going research is focused in the finding of
new drugs that target NCS-1 and disrupt Ric8
interaction to re-establish synapse function in
Fragile X Syndrome and autism.
Figure 5. Details on the molecular surface of dFrq2 and schematic representation of the
activity of the new drugs.
15
Decoding of methylated histone H3
tail by the Pygo-BCL9 Wnt signaling
complex
We are interested in understanding how Pygo
PHD domains, that are histone code readers,
have evolved to recognize different methylation
histone marks that permit the activation of
ß-Catenin/Armadillo dependent transcription of
Wnt signaling genes. Inappropriate activation of
this pathway often leads to cancer, especially
in the intestinal epithelium, thus, it is essential
to understand the mechanism of action of
Pygo protein and its protein-protein interaction
interfaces, which constitute farmacological
targets against colon cancer. In a previous
work, we showed that human and Drosophila
Pygo PHD fingers associate with their cognate
HD1 domains from BCL9/Legless to bind
specifically to the histone H3 tail methylated
at lysine 4 (H3K4me) (Fiedler et al. 2008).
Intriguingly, Drosophilid Pygo orthologs exhibit
a tryptophan>phenylalanine substitution in
their histone pocket-divider which reduces their
affinity for histones. Here (Miller et al. 2013), we
used X-ray crystallography and NMR, to discover
a novel groove bordering this phenylalanine in
the Drosophila PHD-HD1 complex – a semiaromatic cage recognizing asymmetricallymethylated arginine 2 (R2me2a) of the histone
H3 tail, a chromatin mark of silenced genes. Our
structural model of the ternary complex reveals
a new mode of di-methylarginine recognition,
involving a polar interaction between R2me2a
and its groove whose structural integrity is
crucial for normal tissue patterning. Notably,
humanizing fly Pygo enables it to derepress
Notch targets, implying an inherent Notchrelated function of classical Pygo orthologs –
disabled in Drosophilid Pygo orthologs, which
thus appear to be dedicated to Wnt signaling.
Figure 6. Recognition of the histone H3 methylated at Arginine 2 and Lisine 4
(H3R2me2aK4me2) by the Drosophila Pygo-BCL9/Armadillo PHD1-HD1 complex.
16
Structural biology of carbohydrateactive enzymes
Our goal is to unravel de concerted molecular
mechanism of recognition in carbohydrateprocessing enzymes, and their sophisticated
regulatory strategies controlling specificity.
These knowledge is crucial to understand many
biologically relevant process and to undertake
protein
engineering
for
biotechnological
purposes. Our main feats during 2013-14 were
focussed on:
Molecular mechanism involved in plat
cell-wall deconstruction
The plant cell-wall is a highly complex and
heterogeneous network of polymers recalcitrant
to enzymatic attack. Its deconstructions is a
central event in carbon cycle but, also, is of great
interest for the transformation of lignocelluloses
into biofuel and added-value products through a
sustainable industrial activity. The plant cell-wall
degrading enzymes are frequently modular and
contain non-catalytic domains that are revealed
as very interesting tools regulating specificity
and catalytic efficiency. However, modularity
confers flexibility making them a difficult target
for crystallographic studies. Our group has
reported a detailed analysis of Xyn30D, a full
modular enzyme, which has revealed novel
features of its supplementary domain previously
unobserved. By analysis of both, the complete
enzyme and its isolated domains, we have
unravelled the key role of Xyn30D modularity
in deconstruction of highly substituted xylans
(Sainz-Polo et al. 2014).
Figure 7. Xyn30D is a modular enzyme with a very unusual GH35-CBM35 domain architecture
presenting a moderate domain flexibility. Out results assign a key role to Xyn30D in
deconstructing highly substituted xylans through an oriented recognition pattern with its target
substrate (Sainz-Polo et al. 2014)
17
Enzymes producing prebiotics
Fructooligosaccharides (FOS) are polymers
made from fructose units that present prebiotic
activity. Prebiotics are indigestible food
ingredients that selectively stimulate the growth
and maintenance of beneficial gut microbiota,
contributing to prevent cardiovascular disease,
colon cancer and osteoporosis. Different types
of FOS may present enhanced activity profiles
and, therefore, exists an increasing interest in
the development of new compounds with novel
prebiotic efficiency directed to a future preventive
medicine adapted to patient. In this context,
we have improved the transglycosylation
activity of a Ffase from yeast to produce a new
enzyme with a 5.5-fold improvement in fructose
transferase activity over the parental type and
greater selectivity for the synthesis of 6-kestose
(Abreu et al. 2013). We have also reported on
the structure of Saccharomyces invertase, which
catalyzes the hydrolysis of the disaccharide
sucrose into glucose and fructose and also
produces prebiotics. Although invertase is a
fundamental enzyme for sugar metabolism in
yeast and a classical model in early biochemical
studies, its structure was still unkown (SainzPolo et al. 2013). Our results were disclosed to
the media (see below).
Figure 8. Left: Phaffia rhodozyma β-fructofuranosidase is a highly glycosylated enzyme
presenting a novel dimeric structure, mediated by a 100-residues segment inserted at its C-term
and one of the glycan chains. Through molecular analysis of its complexes we have found a
potential activity in producing a broad range of bioconjugates. Right:
Swannyomyces occidentalis Ffase was improved by directed evolution producing a new variant
with enhanced FOS producing activity (Abreu et al. 2013)
18
Structural analysis of protein-lipid
interactions in enzymatic systems
from Lactobacillus plantarum
Protein-lipid interactions occur in a wide range
of physiologically relevant contexts: from
those appearing in biological membranes both
involving integral membrane proteins and
proteins that interact transiently with these
structures, to different enzymatic systems
with lipidic substrates. During the period 20132014 the group of José M. Mancheño has
focused on the structural characterization of
proteín-lipid interactions appearing in different
enzymatic systems from the lactic acid bacteria
Lactobacillus plantarum, particularly esterases/
carboxylesterases and glycerophosphodiester
phosphodiesterases. The most relevant results
obtained were:
Characterization
of
a
novel
carboxylesterase (LpEst1) from L.
plantarum related to the mammalian
hormone-sensitive lipase
The crystal structure of LpEst1 (Álvarez, EstebanTorres et al. 2014) has revealed novel topological
features within the αβ-hydrolase superfamily, as
well as a new dimerization mechanism. Analysis
of the active site has permitted the design of
variants with altered specificity.
Figure 9. The structure of the esterase LpEst1 from Lactobacillus plantarum revealed new
topological features within the α/β hydrolase superfamily as well as a new dimerization mode.
19
Structural analysis and study of the
associative behavior of the esterase
Cest-2923
The combination of crystallographic information
with hydrodynamic data of the enzyme Cest2923
has permitted to understand the complex
pleomorphic behavior of this protein. We have
shown the existence of pH-dependent equilibria
between monomeric, dimeric and tetrameric
species (Benavente et al. 2013).
Functional analysis of a wide array of
esterases from L. plantarum
The objective of the functional characterization
of different esterases from this lactic acid
bacterium is the determination of the optimum
experimental conditions of activity (EstebanTorres et al. 2013, 2014a, 2014b, 2014c). The
perspective of these studies is the potential
application of these enzymes in food industry.
Structural basis of the control of
abiotic stress in plants
Plants have to endure adverse environmental
conditions, among them, drought and salinity
constrain
agricultural
productivity
most
dramatically. Many of the plant adaptive
responses take place at cell membrane where
it is required the regulation o a variety of ion
channels and transporters. This adjusts the
intracellular ion concentration necessary for
cell live. From a molecular point of view, the
levels of abscisic acid (ABA) and calcium encode
the information to orchestrate cell response to
stress. We have discovered and characterized
a new family of proteins, CAR for C2-domain
ABA-related, which target ABA recognition
machinery to the cell membrane. The joined
structural and biochemical analyses has
provided a working model that illustrates how
CAR proteins anchor to plasma membrane and
specifically bind the ABA receptors (Rodriguez
et al. 2014). As the activity of these proteins is
dependent of calcium, they represent a central
hub decoding ABA and calcium stimuli and
provide a target for biotechnological work for
the use of plants in our benefit. In additiom,
we have also studied the CIPK family of twentysix protein kinases that regulates the function of
several ion transporters at the cell membrane to
restore ion homeostasis under stress situations.
Our analyses provide an explanation on how the
CIPKs are differentially activated to coordinate
the adequate cell response to a particular stress
(Chaves-Sanjuan et al. 2014).
Figure 10. CIPK inactivation inhibits the growth of Arabidopsis thaliana model plant in
presence of salt.
20
Scientific outreach and distance
teaching of crystallography
The CBE researchers pay special attention
not only to disseminate their work through a
departmental web page (http://www.xtal.iqfr.
csic.es/) but also to approach the fundamentals
of crystallography to the society at different
levels including both students and the general
scientific community. This program, presented in
terms of a web page (http://www.xtal.iqfr.csic.
es/Cristalografia/) and offered in both Spanish
and English, has become an international
reference
for
crystallographic
teaching.
Although according to Google Analytics,
OneStat.com, o ClustrMaps it receives between
1,000 and 1,500 visits a day, distributed by all
countries, but especially from the US, Europe,
India and Latin American countries. This tutorial
has been selected by the International Union
of Crystallography as one of the web sites of
interest for learning crystallography (http://bit.
ly/1zCsBOX); it has been included as such in the
commemorative website of the International
Year of Crystallography (http://bit.ly/1AvTc0d),
and is offered as one of the best online learning
tools by several US universities (see for example:
http://bit.ly/guMQax).
Figure 11. Snapshot of the welcome web page of the crystallographic tutorial shown in
http://www.xtal.iqfr.csic.es/Cristalografia/. On the right column, the number of user long
sessions during a three weeks period and their most significant countries are shown.
21
Publications
Abdullah, M.R.; Gutiérrez-Fernández, J.;
Pribyl, T.; Gisch,N.; Saleh, M.; Rohde, M.;
Petruschka, L.; Burchhardt, G.; Schwudke,
D.; Hermoso, J.A. and Hammerschmid, S.
(2014). Structure of the pneumococcal L,Dcarboxypeptidase DacB and pathophysiological effects of disabled cell wall hydrolases
DacA and DacB. Molecular Microbiology 93
(6), 1183-1206
Albert, A. (2014). Capítulo de libro: “Comunicación celular a escala atómica” en A
través del cristal. Cómo la cristalografía
ha cambiado la visión del mundo (2014).
(M. Martínez-Ripoll, J.A. Hermoso y Armando
Albert, coord.), CSIC-Catarata, pp. 171-182,
ISBN: 978-84-00-09800-1
Alvarez, L.; Espaillat, A.; Hermoso, J.A.; De
Pedro, M.A. and Cava, F. (2014). Peptidoglycan remodeling by the coordinated action of
multispecific enzymes. Microbial Drug Resistance 20, 1-9
Alvarez, Y.; Esteban-Torres, M.; Cortés-Cabrera, A.; Gago, F.; Acebrón, I.; Benavente,
R.; Mardo, K.; de Las Rivas, B.; Muñoz, R.;
Mancheño, J.M. (2014). Esterase LpEst1 from
Lactobacillus plantarum: a novel and atypical
member of the α/β hydrolase superfamily of
enzymes. PLoS ONE 9(3):e92257
Artola-Recolons, C.; Lee, M.; BernardoGarcía, N.; Blázquez, B.; Hesek, D.; Bartual,
S.; Mahasenan, K.V.; Lastochkin, E.; Pi, H.;
Meindl, K.; Boggess, W.; Uson, I.; Fisher, J.F.;
Mobashery, S. & Hermoso, J.A. (2014). Structure and Cell Wall Cleavage by Modular Lytic
Transglycosylase MltC of Escherichia coli. ACS
Chemical Biology 9 (9), 2058–2066
Baños-Mateos, S., Chaves-Sanjuán, A., Mansilla, A., Ferrús, A., Sánchez-Barrena, MJ.
(2014) Frq2 from Drosophila melanogaster:
cloning, expression, purification, crystallization and preliminary X-ray analysis. Acta
Cryst. Section F 70, 530-534
Bartual, S.G.; Straume, D.; Stamsås, G.A.;
Muñoz, I.G.; Alfonso, C.; Martínez-Ripoll,
M.; Håvarstein, L.S. & Hermoso, J.A. (2014).
Structural basis of PcsB-mediated cell separation in Streptococcus pneumoniae. Nature
Communications 5, Article number 3842
Bernardo, N. and Hermoso J.A. (2014). Capítulo de libro: “Una ventana hacia las enfermedades infecciosas”. En A través del Cristal.
Cómo la cristalografía ha cambiado la
vision del mundo. (Martín Martínez-Ripoll,
Juan A. Hermoso and Armando Albert coord.), CSIC-Catarata, (2014). ISBN: 978-8400-09800Bortolotti, A.; Sánchez-Azqueta, A.; Maya,
C.M.; Velázquez, A.; Hermoso, J.A.; Medina,
M.; Cortez, N. (2014). The C-terminal extension of bacterial flavodoxin-reductases: involvement in the hydride transfer mechanism
from the coenzyme. BBA - Bioenergetics
1837, 33–43
Brabcova, J., Carrasco-Lopez, C., Bavaro T.,
Hermoso, J.A., Palomo, J.M. (2014). Escherichia coli LacZ β-galactosidase inhibition by
monohydroxy acetylated glycopyranosides:
Role of the acetyl groups. J Mol Cata B: Enzym. 107, 31-38
Chaves-Sanjuán A, Sánchez-Barrena MJ,
González-Rubio JM, Albert A. (2014) Preliminary crystallographic analysis of the ankyrinrepeat domain of Arabidopsis thaliana AKT1:
identification of the domain boundaries for
protein crystallization. Acta Crystallographica F70, 509-512
Chaves-Sanjuan, A.; Sanchez-Barrena, M.J.;
Gonzalez-Rubio, J.M.; Moreno, M.; Ragel, P.;
Jimenez, M.; Pardo, J.M.; Martinez-Ripoll, M.;
Quintero, F.J.; Albert, A. (2014) Structural basis of the regulatory mechanism of the plant
CIPK family of protein kinases controlling ion
homeostasis and abiotic stress. Proceedings
of the National Academy of Sciences,
PNAS 111, 4532-4541
Chioua, M.; Samadi, A.; Soriano, E.; Infantes,
L.; Marco-Contelles, J. (2014) Silver TriflateCatalyzed Cyclization of 2-Amino-6-propargylamineazines Leading to Iminoimidazoazines.
Adv. Synth. Catal. 356, 1235-1241
Espaillat, A.; Carrasco-López, C.; BernardoGarcía, N.; Pietrosemolli, N.; Otero, L.H.;
Alvarez, L.; de Pedro, M.A.; Pazos, F.; Davis,
B.M.; Waldor, M.K.; Hermoso, J.A. and Cava, F.
(2014). Structural bases for the broad specificity of a new family of amino acid racemases.
Acta Cryst. D 70, 79-90
22
Esteban-Torres, M.; Barcenilla, J.M.; Mancheño, J.M.; de las Rivas, B.; Muñoz, R. (2014b).
Characterization of a versatile arylesterase
from Lactobacillus plantarum active on wine
esters. J. Agric. Food Chem. 62, 5118-5125
Esteban-Torres, M.; Mancheño, J.M.; de las
Rivas, B.; Muñoz, R. (2014c). Characterization of a cold-active esterase from Lactobacillus plantarum suitable for food fermentations.
J. Agric. Food Chem. 62, 5126-5132
Esteban-Torres, M.; Mancheño. J.M.; de las
Rivas, B.; Muñoz, R. (2014a). Production and
characterization of a tributyrin esterase from
Lactobacillus plantarum suitable for cheese
lipolysis. J. Dairy Sci. 97, 6737-6744
Ferreira, P.; Villanueva, R.; Martínez-Júlvez,
M.; Herguedas, B.; Marcuello, C.; FernandezSilva, P.; Cabon, L.; Hermoso, J.A.; Lostao,
A.; Susin, S.; Medina, M. (2014). Structural
insights into the coenzyme mediated monomer-dimer transition of the pro-apoptotic
Apoptosis Inducing Factor. Biochemistry 53,
4204–4215
Fishovitz, J.; Hermoso, J.A.; Chang, M. &
Mobashery, S. (2014). Penicillin-binding Protein 2a of Methicillin-resistant Staphylococcus
aureus. UBMB Life 66, 572-577
Fishovitz, J.; Rojas-Altuve, A.; Otero, L.H.;
Dawley, M.; Carrasco-López, C.; Chang, M.;
Hermoso, J.A. & Mobashery, S. (2014). Disruption of Allosteric Response as an Unprecedented Mechanism of Resistance to Antibiotics. J. Am. Chem. Soc. 136, 9814–9817
Franco-Echevarria, E., Baños-Sanz, J.I., Monterroso, B., Round A, Sanz-Aparicio, J., Gonzalez, B* (2014). A new calmodulin binding
motif for inositol 1,4,5-trisphosphate 3-kinase
regulation. Biochem J. 463, 319-328
Granell, A.; Rodriguez, P.L. (2014) Tomato
PYR/PYL/RCAR abscisic acid receptors show
high expression in root, differential sensitivity
to the abscisic acid agonist quinabactin, and
the capability to enhance plant drought resistance. Journal of Experimental Botany 65,
4451-4464 Gutiérrez-Fernández, J.; Vaquero, M.E.; Prieto,
A.; Barriuso, J.; Martínez, M.J. and Hermoso,
J.A. (2014). Crystal Structures Of Ophiostoma
Piceae Sterol Esterase: Activation Mechanism
And Product Release. Journal of Structural
Biology 187, 215-222. (portada de la revista)
Hermoso J.A. (2014). Getting CAD in Shape:
The Atomic Structure of Human Dihydroorotase Domain. Structure 22, 179-181
Hermoso, J.A. (2014). Aportaciones de la cristalografía a la medicina. De la comprensión
de las armas moleculares de los patógenos al
desarrollo de fármacos contra enfermedades
infecciosas. Investigación y Ciencia Julio,
Nº. 454, 11-14
Jiménez, N.; Esteban-Torres, M.; Mancheño,
J.M.; de Las Rivas, B.; Muñoz, R. (2014). Tannin degradation by a novel tannase enzyme
present in some Lactobacillus plantarum
strains. Appl. Environ. Microbiol. 80, 29912997.
Martínez-Caballero, S.; Cano-Sánchez, P.;
Mares-Mejía, I.; Díaz-Sánchez, A.; Macías-Rubalcava, M.; Hermoso, J.; Rodríguez-Romero,
A. (2014). Comparative study of two GH19
chitinase-like proteins from Hevea brasiliensis, one exhibiting a novel carbohydrate-binding domain. FEBS Journal 281(19):4535-54
Martínez-Ripoll, M; López Sancho, J.M.; Moreno Gómez, E. (2014) El CSIC cumple 75 años.
Revista Española de Física 28, 25-27
Fulde, M.; Bernardo-García, N.; Rohde, M.;
Nachtigall, N.; Frank, R.; Preissner, K. T.;
Klett, J.; Morreale, A.; Chhatwal, G. S.; Hermoso, J. A. & Bergmann, S. (2014). Pneumococcal phosphoglycerate kinase interacts with
plasminogen and its tissue activator. Thrombosis and Haemostasis 111 3, 401-416
Martínez-Ripoll, M. (2014). Capítulo de libro:
“Una historia con claroscuros plagada de laureados Nobel”. En A través del Cristal. Cómo
la cristalografía ha cambiado la vision del
mundo. (Martín Martínez-Ripoll, Juan A. Hermoso and Armando Albert coord.), CSIC-Catarata, (2014). ISBN: 978-84-00-09800-1
Gonzalez-Guzman, M.; Rodriguez, L.; Lorenzo-Orts, L.; Pons, C.; Sarrion-Perdigones, A.;
Fernandez, M.A.; Peirats-Llobet, M.; Forment,
J.; Moreno-Alvero, M.; Cutler, S.R.; Albert, A.;
Martínez-Ripoll, M.; Hermoso, J.A. & Albert, A.
(2014). Capítulo de libro: “A través del cristal
y más allá”. En A través del Cristal. Cómo
la cristalografía ha cambiado la vision del
23
mundo. (Martín Martínez-Ripoll, Juan A. Hermoso and Armando Albert coord.), CSIC-Catarata. ISBN: 978-84-00-09800-1
Mesa-Torres, N.; Yunta, C.; Fabelo-Rosa, I.;
Gonzalez-Rubio, J.M.; Sanchez-Ruiz, J.M.;
Salido, E.; Albert, A.; Pey, A.L. (2014) The
consensus-based approach for gene/enzyme
replacement therapies and crystallization strategies: the case of human alanine:glyoxylate
aminotransferase. Biochemical Journal 462,
453-463
and preliminary X-ray diffraction analysis of
the N-terminal domain of Paenibacillus barcinonensis xylanase 10C containing the CBM221--CBM22-2 tandem. Acta Crystallogr. F71,
136-140
Sainz-Polo, M.A.Valenzuela, S., Pastor, F.J.,
Sanz-Aparicio, J. (2014). Crystallization
and preliminary X-ray diffraction analysis of
Xyn30D from Paenibacillus barcinonensis.
Acta Crystallogr. F70, 963-6
Rico-Díaz, A., Vizoso-Vázquez, A-, Cerdán,
M.A., Becerra, M., Sanz-Aparicio, J. (2014).
Crystallization and preliminary X-ray diffraction data of β-galactosidase from Aspergillus
niger. Acta Crystallogr. F70, 1529-1531
Sammito, M.; Meindl, K.; de Ilarduya, I.; Millán, C.; Artola-Recolons, C.; Hermoso, J. &
Usón, I. (2014). Structure solution with ARCIMBOLDO using fragments derived from distant homology models. FEBS Journal 281,
4029-4045
Riveron, J.M.; Yunta, C.; Ibrahim, S.S.; Djouaka, R.; Irving, H.; Menze, B.D.; Ismail,
H.M.; Hemingway, J.; Ranson, H.; Albert, A.;
Wondji, C.S. (2014) A single mutation in the
GSTe2 gene allows tracking of metabolically
based insecticide resistance in a major malaria vector. Genome Biology 15, R27
Sanz-Aparicio, J. (2014). Capítulo de libro:
“El arma secreta de la biotecnología” en A
través del cristal. Cómo la cristalografía
ha cambiado la visión del mundo (2014).
(M. Martínez-Ripoll, J.A. Hermoso y Armando
Albert, coord.), CSIC-Catarata, pp. 155-170,
ISBN: 978-84-00-09800-1
Rodriguez, L.; Gonzalez-Guzman, M., Diaz, M.;
Rodrigues, A.; Izquierdo-Garcia, A.C.; PeiratsLlobet, M.; Fernandez, M.A.; Antoni, R.; Fernandez, D.; Marquez, J.A.; Mulet, J.M., Albert,
A.; Rodriguez, P.L. (2014) C2-Domain Abscisic
Acid-Related Proteins Mediate the Interaction
of PYR/PYL/RCAR Abscisic Acid Receptors with
the Plasma Membrane and Regulate Abscisic
Acid Sensitivity in Arabidopsis. The Plant Cell
12, 4802-4820
Silva-Martín, N.; Bartual, S.G.; RamírezAportela, E.; Chacón, P.; Park, C.G. and
Hermoso, J.A. (2014). Structural Basis for
Selective Recognition of Endogenous and Microbial Polysaccharides by Macrophage Receptor SIGN-R1. Structure 22 1595–1606. (portada de la revista)
Romero-Pozuelo, J., Dason, J.S., Mansilla,
A., Baños-Mateos, S., Sardina JL, ChavesSanjuán, A,, Jurado-Gómez, J,, Santana,
E., Atwood, H.L., Hernández-Hernández, A.,
Sánchez-Barrena, M.J., Ferrús, A. (2014) The
binding of a Calcium sensor to a guanine-exchange factor mediates the regulation of synapse number and probability of release. Journal of Cell Science 127(19), 4246-4259
Sainz-Polo, M.A; Valenzuela, S.; González-Pérez, B.; Pastor, F.J.; Sanz-Aparicio, J. (2014).
Structural analysis of glucuronoxylan specific
Xyn30D and its attached CBM35 domain give
insights into the role of modularity in specificity. J. Biol. Chem. 289, 31088-31101
Sainz-Polo, M.A., González-Pérez, B., Pastor,
F.J., Sanz-Aparicio, J. (2014). Crystallization
Silva-Martín, N.; Retamosa, G.; Maestro, B;
Bartual, S.G.; Rodes, M.J.; García, P.; Sanz,
J.M. & Hermoso, J.A. (2014). Crystal structures of CbpF complexed with atropine and ipratropium reveal clues for the design of novel
antimicrobials against Streptococcus pneumoniae. BBA - General Subjects 129-135
Stelter, M.; Molina, R.; Jeudy, S.; Kahn, R.;
Abergel, C. and Hermoso, J.A. (2014). A complement to the modern crystallographer’s
toolbox: caged gadolinium complexes with
versatile binding modes. Acta Cryst. D 70,
1506-1516
Abreu, M., Alvaro-Benito, M., Sanz-Aparicio,
J., Plou, F.J., Fernandez-Lobato, M., Alcalde, M.
(2013). Synthesis of 6-kestose using a highly
efficient β-fructofuranosidase engineered by
directed evolution. Adv. Synth. Catal. 16981702
24
Baños-Sanz, J.I., Mojardín, L., Sanz-Aparicio,
J., Lázaro, J.M., Villar, L., Serrano-Heras, G.,
González, B., and Salas, M., (2013) Crystal
structure and functional insights into uracilDNA glycosylase inhibition by phage ϕ29
DNA mimic protein p56. Nucleic Acids Research 41, 6761-6773
Benavente, R.; Esteban-Torres, M.; Acebrón,
I.; de Las Rivas, B.; Muñoz, R.; Alvarez, Y.;
Mancheño, J.M. (2013). Structure, biochemical characterization and analysis of the pleomorphism of carboxylesterase Cest-2923 from
Lactobacillus plantarum WCFS1. FEBS J. 280,
6658-6671
Bouit, P.A.; Infantes, L.; Calbo, J.; Viruela,
R.; Ortí, E.; Delgado, J.L.; Martín, N. (2013)
Efficient Light Harvesters based on the
10-(1,3-Dithiol-2-ylidene)anthracene
core.
Org. Lett. 15, 4166-4169
Chioua, M.; Soriano, E.; Infantes, L.; Jimeno,
M.L.; Marco-Contelles, J.; Samadi, A. (2013)
The Silver-catalyzed Cyclization of N-(prop2-yn-1-yl)pyridin-2-amines. Eur. J. Org.
Chem. 35-39
Durante-Rodríguez, G.; Mancheño, J.M.; Rivas, G.; Alfonso, C.; García, J.L.; Díaz, E.; Carmona, M. (2013). Identification of a missing
link in the evolution of an enzyme into a transcriptional regulator. PLoS ONE 8(3):e57518
Engel, H.; Gutiérrez-Fernández, J.; Flückiger,
C.; Martínez-Ripoll, M.; Mühlemann, K.; Hermoso, J.A.; Hilty, M.; Hathaway, L.J. (2013).
Heteroresistance to fosfomycin is predominant
in Streptococcus pneumoniae and depends
on murA1 gene. Antimicrobial Agents and
Chemotherapy 57 (6), 2801-1808
Esteban-Torres, M.; Reverón, I.; Mancheño,
J.M.; de Las Rivas, B.; Muñoz, R. (2013).
Characterization of a feruloyl esterase from
Lactobacillus plantarum. Appl. Environ. Microbiol. 79, 5130-5136
Fernández de la Pradilla, R.; Simal, C.; Bates,
R.H.; Viso, A.; Infantes, L. (2013) SulfoxideDirected Enantioselective Synthesis of Functionalized Tetrahydropyridines. Org. Lett. 15,
4936-4939
Infantes, L.; García, M.A.; López, C.; Claramunt, R.M.; Elguero, J. (2013) The Structure and Dynamic Properties of 1H-Pyrazole-
4-carboxylic acids in the Solid State. Z. Phys.
Chem. 227, 841-856
Lee, M.; Artola-Recolons, C.; Carrasco-López,
C.; Martínez-Caballero, S.; Hesek, D.; Spink,
E.; Lastochkin, E.; Zhang, W.; Hellman, L.;
Boggess, B.; Hermoso, J.A. & Mobashery, S.
(2013). Cell-Wall Remodeling by the Zinc-Protease AmpDh3 from Pseudomonas aeruginosa. J. Am. Chem. Soc. 12605-12607
Martínez-Caballero, S.; Lee, M.; Artola-Recolons, C.; Carrasco-López,C.; Hesek, D.; Spink,
E.; Lastochkin, E.; Zhang, W.; Hellman, L.M.;
Boggess, B.; Mobashery, M. and Hermoso,
J.A. (2013). Reaction products and the X-ray
structure of AmpDh2, a virulence determinant
of Pseudomonas aeruginosa. J. Am. Chem.
Soc. 135; 10318-10321
Martínez-Ripoll, M. (2013). ¿Cómo aprendimos a “ver” los átomos? En El CSIC en la Escuela, Investigación sobre la enseñanza
de la ciencia en el aula, 9, pp. 9-34, e-ISBN
(n. 9): 978-84-00-09659-5
Mesa-Torres, N.; Fabelo-Rosa, I.; Riverol, D.;
Yunta, C.; Albert, A.; Salido, E.; Pey, A.L.
(2013) The role of protein denaturation energetics and molecular chaperones in the aggregation and mistargeting of mutants causing
primary hyperoxaluria type I. PLoS ONE 8,
e71963
Miller, T.C.R., Mieszczanek, J., Sánchez-Barrena, M.J., Rutherford, T.J., Fiedler, M., Bienz,
M. (2013) Evolutionary Adaptation of the Fly
Pygo PHD Finger toward Recognizing Histone
H3 Tail Methylated at Arginine 2. Structure
21(12), 2208-2220
Otero, L.H.; Rojas-Altuve, A., Llarrull, L.I.;
Kumarasiri, M.; Lastochkin, E.; Fishovitz, J.;
Dawley, M.; Hesek, D.; Lee, M.; Johnson,
J.W.; Fisher, J.F.; Chang, M.; Mobashery, S.
and Hermoso, J.A. (2013). How allosteric control of Staphylococcus aureus penicillin-binding protein 2a enables methicillin-resistance
and physiological function. PNAS 110, 1680816813
Pérez-Dorado I., Bortolotti A., Cortez N., Hermoso, J.A. (2013) Structural and Phylogenetic
Analysis of Rhodobacter capsulatus NifF: Uncovering General Features of Nitrogen-fixation
(nif)-Flavodoxins. International Journal of
Molecular Sciences 14(1):1152-1163
25
Pérez-Faginas, P.; Aranda, M.T.; GarcíaLópez, M.T.; Infantes, L.; Fernández-Carvajal,
A.; González-Ros, J.M.; Ferrer-Montiel, A.;
González-Muñiz, R. (2013) Highly functionalized β,γ–diamino compounds through reductive amination of amino acid-derived β–keto
esters. PLoS ONE 8(1), e53231
Sainz-Polo, M.A., Ramírez, M., Lafraya, A.,
González, B., Marín-Navarro, J., Polaina, J.,
Sanz-Aparicio, J. (2013). The three-dimensional structure of Saccharomyces invertase:
role of a non-catalytic domain in oligomerization and substrate specificity. J. Biol. Chem.
288, 9755-9766
Pey, A.L.; Albert, A.; Salido, E. (2013) Protein homeostasis defects of alanine-glyoxylate
aminotransferase: new therapeutic strategies
in primary hyperoxaluria type I. Biomed Research International 2013:687658
Saleh, M.; Bartual, S.G.; Abdullah, M.R.;
Jensch, I.; Asmat, T.M.; Petruschka, L.; Pribyl, T.; Hermoso, J.A. and Hammerschmidt S.
(2013). Molecular architecture of Streptococcus pneumoniae surface thioredoxin-fold lipoproteins crucial for extracellular oxidative
stress resistance and maintenance of virulence. EMBO Molecular Medicine 5, 18521870 (portada de la revista)
Pizzio, G.A.; Rodriguez, L.; Antoni, R.;
González-Guzman, M.; Yunta, C.; Merilo, E.;
Kollist, H.; Albert, A.; Rodriguez, P.L. (2013)
The PYL4 A194T mutant uncovers a key role of
PYR1-LIKE4/PROTEIN PHOSPHATASE 2CA interaction for abscisic acid signaling and plant
drought resistance. Plant Physiology 163,
441-55
Sánchez-Barrena, M.J.; Martínez-Ripoll, M.;
Albert, A. (2013) Structural Biology of a Major
Signaling Network that Regulates Plant Abiotic
Stress: The CBL-CIPK Mediated Pathway. Int.
J. Mol. Sci. 14, 5734-5749
26
COMPETITIVE FUNDING
National Grants: individual
CSIC
Principal Investigator
TitleReference
Juan A. Hermoso
Maquinas moleculares de remodelado de pared bacteriana en patógenos multiresistentes:
aplicaciones al desarrollo de nuevos fármacos
Juan A. Hermoso
Bases estructurales de los mecanismos bacterianos I-LINK0319
de patogenicidad y resistencia a antibióticos
I-LINK0864
MINECO
TitleReference
Juan A. Hermoso
Biologia estructural de proteinas de la pared celular BFU2011-25326
bacteriana: implicaciones en las interacciones
hospedador-patogeno
Structural biology of inositol phosphates signalling: BFU2011-24982
regulation by kinases and function in mrna export.
Jose Miguel Mancheño
Biología estructural de enzimas lipolíticas y gdpds de la bacteria láctica lactobacillus plantarum wcfs1
Armando Albert
Biologia estructural de la tolerancia hidrica y salina BFU2011-25384
en plantas. Papel del calcio y del acido abcisico
BFU2010-17929
27
National Grants: coordinated
Government of Madrid
TitleReference
Federico Gago
Juan A. Hermoso
(PI grupo IQFRRX)
Armando Albert
(PI Laboratorio DRX)
Plataforma integrada de bioinformática para el descubrimiento de nuevos fármacos basado
en la estructura del receptor- BIPEDD2
S2010/BMD-2457
MINECO
TitleReference
María José Sánchez Barrena
Biología estructural de complejos SCF(SKP2A) de la ruta ubiquitina/proteasoma en plantas
Juliana Sanz Aparicio
Analisis cristalografico de los determinantes BIO2013-48779-C4-2-R
moleculares de la especificidad en nuevas enzimas de interes biotecnológico
Mecanismos moleculares de reconocimiento e BIO2010-20508-C04-03.
hidrólisis de carbohidratos: estructura de
glicosidasas modulares y de sus complejos con
oligosacáridos mediante cristalografía de proteínas.
BIO2011-28184-C02-02
International Grants: individual
European Union
TitleReference
Structural biology of SCF(SKP2A) E3 ligase complexes of the ubiquitin/ proteasome pathway
in plants: Auxin perception for cell division control
INSTRUCT-388
International Grants: coordinated
National Institutes of Health USA (NIH)
TitleReference
Mayland Chang (PI)
Juan A. Hermoso (PI WP)
Novel Oxadiazols for the Treatment of Drug-1R01AI090818-01
Resistant Gram-Positive Bacteria
28
Department of Structure, Energy
and Chemical Reactivity
Memoria 2013/2014 Department of Crystallography
30
Introduction
The Department of Structure, Energy and
Chemical Reactivity has been formed during
the biennium 2013-2014 by 8 research
scientists:
• Professor: Rafael Notario Bueno.
• Associate Professors: Rosa Becerra Arias
and Alfonso Saiz-López.
• Assistant Professors: Juan Z. Dávalos
Prado, Pablo Echenique Robba, Rosa
Lebrón Aguilar, Josep M. Oliva Enrich and
Jose María Santiuste Bermejo.
The Department carries out different research
lines exposed in the memories of the groups.
The main objectives are: the study of the
reactivity (by proton-interchange processes),
structural effects on the gas phase acidity/
basicity and thermodynamic stability of
species with biological activity and/or
technological and environmental relevance;
the study of the dynamics of photodissociation
(energy ranges of UV and X-ray) of organic
species with heteroatoms of N, S and Cl; the
development of methodologies; the study
of the chemistry of heteroborane clusters,
and their interactions with biomolecules;
the studies of new reaction kinetic of silicon
and germanium containing heavy carbenes
of interest in the materials industry; the
development and characterization of new
stationary phases for gas chromatography
based on ionic liquids; the determination
of chromatographic and thermodynamic
parameters by gas chromatography; the
development of advanced analytical methods
by chromatography and mass spectrometry;
the exploration of the interactions between
anthropogenic and natural emissions, the
chemical and physical climate system, and
the biosphere, within a changing climate
context; and the evaluation and improvement
of molecular simulation methods.
We have in the Department different
experimental
techniques:
combustion
calorimetry with rotatory, static and semimicro
bombs;
combustion
microcalorimetry
(CMRT); diferential scanning calorimetry
(DSC); Knudsen efussion technique; FT-ICR
(Fourier transform ion cyclotron resonance)
high resolution mass spectrometry of 4.7 T
and 7.0 T (with ESI and MALDI sources);
laser flash photolysis; gas chromatographs
for capillary and packed columns, with flame
ionization detectors; gas chromatograph
coupled to a quadrupolar mass spectrometer,
fitted with sample introduction systems
for liquids and gases; diffferential Optical
Absorption
Spectroscopy
(DOAS)/onground, ship, airborne and satellite based
instrument; resonance and off resonance
fluorescence by lamp excitation (ROFLEX)/
on-ground, airborne; Incoherent Broadband
Cavity Enhanced Absorption Spectroscopy
(IBBCEAS); chemiluminiscence NOx.
Scientific Report 2013/2014 Department of Structure, Energy and
31
Chemical Reactivity
Groups Structure
Energetics, Structure and Molecular Interactions
33
Photolysis and Chromatography
42
Atmospheric Chemistry and Climate
51
32
Chemical Reactivity
Energetics, Structure and Molecular
Interactions Group
Tenured Staff scientists
Juan Z. Dávalos Prado (Assistant Professor) ReID ORCID
Rafael Notario Bueno (Professor) ReID ORCID
Josep M. Oliva Enrich (Assistant Professor)
Doctoral students
Francisco Javier González (until 08/2014)
Technical Staff
Rocío Ramos Novillo (JAE Tec) (until 01/2013)
33
Chemical Reactivity
Summary
We study chemical reactivity, energetic
properties, interactions and structure of
neutral and ionic species – in the gas phaseof fundamental, biological and technological
relevance. For this purpose we use a variety
of experimental (Linear Triple Quadrupole TQ
/Fourier Transform Ion Cyclotron Resonance
FT-ICR Mass Spectrometer with ESI/MALDI
sources; calorimetry of combustion; Knudsen’s
effusion; photoelectron-photoion coincidence
spectroscopy
PEPICO)
and
theoretical
techniques. The combination of the experimental
results with those obtained by means of
quantum-mechanic calculations (ab-initio, DFT)
allow us to: i) obtain quantitative information
on thermodynamics and kinetics of a variety
of ion-molecule reactions in the phase gas, ii)
determine interesting and novel relationship
of reactivity-chemical structure, iii) determine
the thermodynamic stability of neutral and
ionic species, iv) study the reactivity, energetic
properties and fragmentation mechanisms of
organic and organometallic species (from small
to macromolecular fragments).
Strategic Aims
Our research lines focus on the quantitative study of the energetic properties, structure,
chemical reactivity and dynamics of dissociation of ions and molecules (organic, inorganic and
organometallic) in the absence of the disturbing effect of the solvent.
The specific goals pursued are:
• Reactivity (by proton-interchange processes), structural effects on the gas phase acidity/
basicity and thermodynamic stability of species such as amine-borane complexes, carboranes,
phenolic acids, bisphenols and other compounds with biological activity, technological and
environmental relevance.
• Study of the dynamics of photodissociation (energy ranges of UV and X-ray) of organic
species with heteroatoms of N, S and Cl.
• Development of methodologies, using hybrid triple quadrupole and FT-ICR high-resolution
mass spectrometry, to study: i/ the reactivity, energetic properties and fragmentation
mechanisms of thermolabile molecules, ii/ the interactions among macromolecules and
several organic and organometallic species, iii/ characterization of macromolecule fragments
and analysis of complex-mixtures (including metabolites), iv/ elucidation of fine details in
problems of sequenciation of biomolecules.
• Electronic structure of heteroborane clusters (HBC) in their ground and excited states.
• Construction of molecular architectures based on HBCs in different dimensions, computational
and experimental studies of their properties.
• Theoretical and experimental studies of the interaction HBC·and·biomolecules.
34
Chemical Reactivity
Results
Gas phase acidity measurement of
local acidic groups in multifunctional
species
We have determined the acidity GA -in the
gas phaseof the hydroxyl and carboxyl
local groups of the hydroxycinnamic acids,
applying the kinetic method (EKM) in a mass
spectrometer with electrospray (ESI)-source.
Hydroxycinnamic acids are natural compounds
found in several biological sources mostly in the
plant kingdom either as esters of organic acids
or glycosides, bound to proteins or as free acids
The most important contribution of this work
has been to show that is possible to determine
gas-phase acidities (GAs) or basicities (GBs)
of different deprotonation or protonation sites
of a same molecule, only by a careful control
of the ESI-experimental conditions; since the
measurement of GA or GB of monofunctional
molecules not offer a new scientific challenge.
Energetics and Structural Properties
of bisphenols in the gas phase
We have carried out studies of the energetics,
structure, and thermophysical properties (phase
equilibria thermodynamics) of bisphenols A, E, F,
AP and S. In particular, the standard enthalpies
of sublimation and the standard enthalpies of
formation in the gas phase, ∆fHm0(g), for all
these species were experimentally determined.
A computational study, through M05-2X Density
Functional Theory, of the various species shed
light on structural effects and further confirmed,
by means of isodesmic reactions scheme, the
excellent consistency of the experimental
results. Our results reflect also the fact that
energetic substituent effects are transferable
from diphenylalkanes to bisphenols.
This work opens the implementation of new
experimental methodologies (e.g. using ESI-MS)
to extract and quantify reliable thermodynamic
properties, such as GA or GB, of different local
groups within a multifunctional molecule.
35
Chemical Reactivity
Chemical reactivity and interactions
of icosahedral closo-(car)boranes
A Linear ESI-TQ-FT-ICR mass spectrometer
combines the highest available mass accuracy
with advanced MS/MS capabilities and is
perfectly suited to study the interactions of
icosahedral closo-(car)boranes Li2[B12H12] (I)
and Li[CB11H12] (II). The experimental results
are explained and rationalized by quantumchemical studies, finding the most stable
structures of I, II, and their derived cluster
anions.
Comparison of the constants for protonation−
deprotonation microscopic equilibria in the
ortho, meta, and para isomers of carborane
amino acids with those for the corresponding
amino benzoic acids is given. A remarkable
difference is found between the proportion of
neutral versus zwitterion structures in water for
glycine and the carborane derived amino acids.
According to the experimental results, the
dianion B12H122− shows a bigger affinity for lithium
than the monoanion CB11H12−. Signals of oligomer
anions of singly and doubly charged have been
detected which were identified, respectively, as
[In−Li]− (n = 1, 2, 3, 4) and [In−2Li]2− (n = 1,
4, 5, 6, 7). As for II, only monomer and dimer
singly charged anions [IIn−Li]− (n = 1, 2) were
detected.
We have studied also, both experimentally and
computationally, the gas-phase acidity (GA =
1325 kJ·mol−1) and liquid-phase acidity (pKa =
2.00) of the carborane acid closo-1-COOH-1,7C2B10H11. The experimental GA was determined
by using the extended Cooks kinetic method
(EKM).
36
Chemical Reactivity
Photodissociation
of
organic
molecules by Synchrotron Radiation
(VUV range)
Photoelectron photoion coincidence PEPICO
measurements have been performed for the
thiazole (C3H3NS) molecule in gas phase, using
time-of-flight mass spectrometry in the electronion coincidence mode and vacuum ultraviolet
synchrotron radiation. PEPICO spectra have
been recorded as a function of the photon energy
covering the valence range from 10 to 21eV.
The resulting photoionization products as well
as the dissociation pathways leading to the ionic
species were proposed and discussed. We have
also performed DFT and ab initio calculations
for the neutral molecule, its cation and the ion
fragments produced in order to determine their
electronic and structural parameters.
Characterization
and
structural
properties of metallic complexes
A new silver–chloroquine (CQ–Ag) complex has
been synthesized and characterized by using
a combination of NMR (solution and solidstate), FTIR, molar conductivity and ESI/FT-ICR
high resolution mass spectroscopy with DFT
calculations. The CQ–Ag complex is formed by
silver–CQ cations and nitrate counter anions,
where the silver atoms are di-coordinated to
chloroquines (CQ2Ag2+) through the quinoline
sp2 N and diethylamino sp3 N nitrogen basic
sites. These cations presumably form polymeric
structures mainly as head–head catemers. The
most important cationic fragments of the CQ–Ag
complex, detected by ESI/FT-ICR, were CQAg+,
CQ2Ag+, chloroquine singly (CQH+) and doubly
protonated (CQH22+), whose formations are
clearly favored by proton-displacement of the
Ag+ cations.
37
Chemical Reactivity
Thermochemical study
acids and derivatives
of
amino
Following the studies started in the last years,
we have published in the last two-year period
five new studies on amino acids and derivatives:
cyclic anhydrides of glycine and alanine,
sarcosine and its cyclic anhydride, N-acetylL-cisteine, proline, and selenocysteine. All the
studies were experimental and theoretical,
except that on selenocysteine, which was only
theoretical.
The standard molar enthalpies of formation in
the crystalline phase of the studied compounds
were calculated from the standard molar
energies of combustion in oxygen, measured
by static bomb combustion calorimetry. The
standard molar enthalpies of sublimation were
derived from the Clausius-Clapeyron equation,
from the vapor pressures measured as function
of temperature by the Knudsen effusion massloss technique, except in the case of N-acetylL-cisteine, which enthalpy of sublimation could
not be determined due to the decomposition of
the compound during the experiments. From
those experimental values, the standard molar
enthalpies of formation in the gas phase of the
studied compounds were calculated.
Theoretical studies for all the compounds were
carried out at the G3 and G4 levels, doing
conformational analyses and calculating their
enthalpies of formation through atomization
and/or isodesmic reactions, observing in all
cases a good agreement between experimental
and computational values.
Thermochemical study of nitrogencontaining heterocycles
Following a line of work launched some years
ago, and in which we continue working, on the
thermochemical study of nitrogen-containing
heterocycles, we have carried out in this
biennium two experimental and theoretical
studies on barbituric acid derivatives: one
on 1,3,5-trimethyl-, 1,5,5-trimethyl-, and
1,3,5,5-tetramethylbarbituric acids, and the
other on 1,3-diethylbarbituric and 1,3-diethyl2-thiobarbituric acids, as well as a computational
study on 2-selenobarbituric acid, in which
the intrinsic acidity and basicity have been
calculated, resulting that this compound is a
very strong Brønsted acid in the gas phase.
Another study was devoted to study three
uracils: 5,6-dimethyl-, 1,3,5-trimethyl-, and
1,3,5,6-tetramethyluracils.
Combustion energies were measured using static
bomb combustion calorimetry, and from them
the standard molar enthalpies of formation in
the crystalline state were obtained. Sublimation
enthalpies were determined by the transference
(transpiration) method in saturated nitrogen
flow.
Theoretical calculations at the G3 and G4 levels
were performed, and a study on molecular
and electronic structures of the compounds
has been carried out. Calculated enthalpies of
formation are in very good agreement with the
experimental values.
Thermochemical study of fluorene
derivatives
This is a research line started in the previous
biennium in which we study, experimentally
and computationally, the thermochemistry of
fluorene derivatives.
Two papers have been published in this
biennium: First, we have studied fluorene9-methanbol and fluorene-9-carboxylic acid,
and then, 2-nitro- and 2-aminofluorene.
Combustion enthalpies have been determined
using static bomb calorimetry, and sublimation
enthalpies from Knudsen effusion technique.
The corresponding enthalpies of formation have
been calculated at the G3 and G4 levels. There
is a good agreement between experimental and
theoretical values.
Computational
mechanisms
study
reaction
Theoretical calculations at MP2 or DFT levels of
theory have been carried out in order to explore
the nature of the mechanism of the thermal
decomposition reaction of two β-hydroxy
alkenes: 3-buten-1-ol and 3-methyl-3-buten1-ol in m-xylene solution. The mechanism
proposed is a one-step process proceeding
through a six-membered cyclic transition state.
The progress of the decomposition reactions
has been followed by means of the Wiberg bond
indices, calculated using a population partition
technique, the natural bond orbital (NBO)
analysis.
38
of
Chemical Reactivity
Publications
Santos, A.F.L.O.M.; Amaral, L.M.P.F.; Ribeiro
da Silva, M.D.M.C.; Roux, M.V.; Notario, R.
(2013). Experimental and Computational
Study on the Energetics of the Cyclic
Anhydrides of Glycine and Alanine. J. Chem.
Thermodyn. 58, 29-35.
Amaral, L.M.P.F.; Santos, A.F.L.O.M.; Ribeiro
da Silva, M.D.M.C.; Notario, R. (2013).
Thermochemistry of Sarcosine and Sarcosine
Anhydride: Theoretical and Experimental
Studies. J. Chem. Thermodyn. 58, 315-321.
Notario, R.; Emelýanenko, V.N.; Roux, M.V.;
Ros, F.; Verevkin, S.P.; Chickos, J.S.; Liebman,
J.F. (2013). Thermochemistry of Uracils.
Experimental and Computational Enthalpies of
Formation of 5,6-Dimethyl-, 1,3,5-Trimethyl-,
and 1,3,5,6-Tetramethyluracils. J. Phys.
Chem. A 117, 244-251.
Pabon, A.; Escobar, G.; Vargas, E.; Cruz, V.;
Notario, R.; Blair, S.; Echeverri, F. (2013).
Diosgenone Synthesis, Anti-Malarial Activity
and QSAR of Analogues of This Natural
Product. Molecules 18, 3356-3378.
Vegas, A.; Notario, R.; Chamorro, E.; Pérez,
P.; Liebman, J.F. (2013). Isoelectronic and
Isolobal O, CH2, CH3+ and BH3 as Electron
Pairs; Similarities between Molecular and
Solid-state Chemistry. Acta Cryst. B 69, 163175.
Chamorro, E.; Duque-Noreña, M.; Notario, R.;
Pérez, P. (2013). Intrinsic Relative Scales of
Electrophilicity and Nucleophilicity. J. Phys.
Chem. A 117, 2636-2643.
Oliveira, J.A.S.A.; Calvinho, M.M.; Notario,
R.; Monte, M.J.S.; Ribeiro da Silva, M.D.M.C.
(2013). A Combined Experimental and
Computational Thermodynamic Study of
Fluorene-9-methanol
and
Fluorene-9carboxylic acid. J. Chem. Thermodyn. 62,
222-230.
Liebman, J.F.; Chickos, J.S.; Notario, R.
(2013). Maria Victoria Roux, Colleague,
Calorimetrist, and Friend. Struct. Chem. 24,
1785-1787.
Lopez, V.; Quijano, J.; Luna, S.; Ruiz, P.; Ríos,
D.; Parra, W.; Zapata, E.; Gaviria, J.; Notario,
R. (2013). Experimental and Computational
Study of the Thermal Decomposition of
3-Buten-1-ol in m-Xylene Solution. Struct.
Chem. 24, 1811-1816.
Notario, R.; Klapoetke, T.M.; Liebman, J.F.
(2013). The Gas Phase Enthalpies of Formation
of Hydrazine, its Methylated Derivatives, and
the Corresponding Values for Ammonia and its
Methylated Derivatives. Struct. Chem. 24,
1817-1819.
Juaristi, E.; Notario, R. (2013). Computational
Reexamination of the Eclipsed Conformation
in cis-2-tert-butyl-5-(tert-butylsulfonyl)-1,3dioxane. Struct. Chem. 24, 1855-1862.
Perisanu, S.; Contineanu, I.; Neacsu, A.; Rath,
N.P.; Chickos, J.S.; Notario, R.; Liebman, J.F.
(2013). Thermochemical and Structural Study
of a Dibenzocycloheptane Cyanoenamine.
Struct. Chem. 24, 1975-1980.
Dávalos, J.Z., González, J.; Guerrero, A.;
Hnyk, D.; Holub, J.; Oliva, J.M. (2013). Anionic
Oligomerization of Li2[B12H12] and Li[CB11H12]:
An Experimental and Computational Study. J.
Phys. Chem. C 117, 1495-1501.
Golon, A.; González, J.; Dávalos, J.Z.;
Kuhnert, N. (2013). Investigating the Thermal
Decomposition of Starch and Cellulose in
Model Systems and Toasted Bread Using
Domino Tandem Mass Spectrometry. J. Agric.
Food Chem. 61, 674-684.
Dávalos, J.Z.; González, J.; Guerrero, A.;
Valderrama-Negrón, A.C.; Aguirre Méndez,
L.D.; Claramunt, R.M.; Santa María, D.;
Alkorta, I.; Elguero, J. (2013). Silver complex
of chloroquine: synthesis, characterization
and structural properties. New J. Chem. 31,
1391-1401.
Guerrero, A.; Baer, T.; Chana, A.; González,
J.; Dávalos, J.Z. (2013). Gas Phase Acidity
Measurement of Local Acidic Groups in
Multifunctional Species: Controlling the
Binding Sites in Hydroxycinnamic Acids. J.
Am. Chem. Soc. 135, 9681-9690.
Dávalos, J.Z.; Jiménez, P.; Roux, M.V.; Molina,
M.T.; Filipova, T.; Lewars, E.; Liebman, J.
(2013). Thermochemical and structural
properties of anthraquinones”. Struct. Chem.
24, 2027-2034.
Oliva, J.M.; Alcoba, D.R.; Lain, L,; Torre,
A. (2013). Electronic structure studies of
diradicals derived from closo-carboranes.
Theor. Chem. Acc. 132, 1329-1, 1329-6.
Saurí, V.; Oliva, J.M.; Hnyk, D.; Bould,
J.; Braborec, J.; Merchán, M.; Kubát, P.;
Císarová, I.; Lang, K.; Londesborough, M.G.S.
(2013). Tuning the photophysical properties
of anti-B18H22: Quantum hopping between
excited singlet and triplet states in new antiB18H20(SH)2. Inorg. Chem. 52, 9266-9274.
Oliva, J.M. (2013). Julio Palacios Martínez
39
Chemical Reactivity
(1891-1970): Un científico entre la física y la
química. An. Quim. 109, 106-109.
Oliva, J.M.; Rué, J.; Hnyk, D.; Kennedy, J.D.;
Rosenfeld, V.R. (2013). Borane polyhedra as
building blocks for unknown but potentially
isolatable new molecules – Extensions based
on computations of the known B18H22 isomers.
Croat. Chem. Acta. 86, 485-494.
Notario, R.; Roux, M.V.; Santos, A.F.L.O.M.;
Ribeiro
da
Silva,
M.D.M.C.
(2014).
Experimental and Computational Study on the
Energetics of N-Acetyl-L-cysteine. J. Chem.
Thermodyn. 73, 57-61.
Temprado, M.; Notario, R.; Roux, M.V.;
Verevkin, S.P. (2014). Thermochemistry of
Methoxythiophenes: Measurement of their
Enthalpies of Vaporization and Estimation of
their Enthalpies of Formation in the Condensed
Phase. J. Chem. Thermodyn. 73, 97-100.
Notario, R.; Chickos, J.S.; Liebman, J.F. (2014).
The Enthalpy of Formation of Selenocysteine:
A G3 and G4 Quantum Chemical Study. J.
Chem. Thermodyn. 73, 134-139.
Notario, R.; Roux, M.V.; Ros, F.; Emelýanenko,
V.N.; Verevkin, S.P. (2014). Experimental
and Computational Thermochemical Study
of 1,3,5-Trimethyl-, 1,5,5-Trimethyl-, and
1,3,5,5-Tetramethyl-barbituric
Acids.
J.
Quijano, J.; Ruiz, P.; Notario, R.; Zapata,
E.; Gaviria, J. (2014). Experimental and
Computational
Study
of
the
Thermal
Decomposition of 3-Methyl-3-buten-1-ol in
m-Xylene Solution. Int. J. Chem. Kinet. 46,
363-369.
Notario, R. (2014). A Computational Study
of 2-Selenobarbituric Acid: Conformational
Analysis, Enthalpy of Formation, Acidity and
Basicity. Procedia Comput. Sci. 29, 13561365.
Oliveira, J.A.S.A.; Monte, M.J.S.; Notario,
R.; Ribeiro da Silva, M.D.M.C. (2014).
Experimental and Computational Study of the
Thermodynamic Properties of 2-Nitrofluorene
and 2-Aminofluorene. J. Chem. Thermodyn.
76, 56-63.
Notario, R.; Roux, M.V.; Ros, F.; Emelýanenko,
V.N.; Zaitsau, D.H.; Verevkin, S.P. (2014).
Thermochemistry of 1,3-Diethylbarbituric
and
1,3-Diethyl-2-thiobarbituric
Acids:
Experimental and Computational Study. J.
Santos, A.F.L.O.M.; Notario, R.; Ribeiro da
Silva, M.A.V. (2014). Thermodynamic and
Conformational Study of Proline Stereoisomers.
J. Phys. Chem. B 118, 10130-10141.
Freitas, V.L.S.; Leirosa, S.; Notario, R.; Ribeiro
da Silva, M.D.M.C. (2014). Thermochemical
Insights on the Conformational Energetics
of Azepan and its Azepan-1-ylacetonitrile
Derivative. J. Org. Chem. 79, 11583-11591.
Rodríguez-Bencomo, J.J.; Andújar-Ortiz, I.;
Moreno-Arribas, M.V., Simó, C.; González,
J.; Chana, A.; Dávalos, J.Z.; Pozo-Bayón,
M.A. (2014). Impact of Glutathione-Enriched
Inactive Dry Yeast Preparations on the Stability
of Terpenes during Model Wine Aging. J. Agric.
Food Chem. 62, 1373-1383.
Dávalos, J.Z.; González, J.; Ramos, R.;
Guerrero, A.; Lago, A.F. (2014). Intrinsic (gasphase) acidity and basicity of paracetamol.
Arkivoc (ii) 150-160.
Dávalos, J.Z.; González, J.; Ramos, R.; Hnyk,
D.; Holub, J.; Santaballa, J.A.; Canle-L, M.;
Oliva, J.M. (2014): Acidities of closo-1-COOH1,7-C2B10H11 and Amino Acids Based on
Icosahedral Carbaboranes. J. Phys. Chem. A
118, 2788-2793.
Dávalos, J.Z.; Herrero, R.; Costa, J.C.S.;
Santos, L.M.N.B.F.; Liebman, J.F. (2014).
Energetic and Structural Study of Bisphenols”.
J. Phys. Chem. A 118, 3705-3709.
Costa, J.C.S.; Dávalos, J.Z; Santos, L.M.N.B.F.
(2014). Phase Transition Thermodynamics of
Bisphenols. J. Phys. Chem. A 118, 97129719.
Alkorta, I.; Cancedda, C.; Cocinero, E.J.;
Dávalos, J.Z.; Écija, P.; Elguero, J.; González,
J.; Lesarri, A.; Ramos, R.; Reviriego, F.;
Roussel, Ch.; Uriarte, I; Vanthuyne, N. (2014).
Static and Dynamic Properties of 1,1’-Bi-2naphthol and Its Conjugated Acids and Bases.
Chem. Eur. J. 20, 14816-14825.
Lago, A.F.; Januário, R.D.; Simon, M.;
Dávalos, J.Z. (2014). VUV photodissociation
of thiazole molecule investigated by TOFMS and photoelectron photoion coincidence
spectroscopy. J. Mass Spectrom. 49, 11631170.
Alcoba, D.R.; Torre, A.; Lain, L.; Oña,
O.B.; Oliva, J.M. (2014). Determination of
Heisenberg exchange coupling constants
in clusters with magnetic sites: A local spin
approach. Int. J. Quantum Chem. 114, 952958.
Bhattacharya, D.; Klein, D.J.; Oliva, J.M.;
Griffin, L.L.; Alcoba, D.R.; Massaccesi,
G.E. (2014). Icosahedral symmetry supercarborane & beyond. Chem. Phys. Lett. 616617, 16-19.
40
Chemical Reactivity
COMPETITIVE FUNDING
Ministerio de Ciencia e Innovación (MICIMM)
TitleReference
Rafael Notario Bueno
Termoquímica Experimental y Computacional: Relación Estructura-Energía en Heterociclos
Nitrogenados de Interés Biológico
CTQ2010-16402
Juan Z. Dávalos Prado
Gas-phase reactivity, energetics, structure and interactions of neutral and ionic species of
fundamental biological and technological relevance
CTQ2009-13652
CSIC
TitleReference
Josep M. Oliva
Diseño de imanes moleculares en base al boro mediante técnicas computacionales
ICOOP-B20040
41
Chemical Reactivity
Photolysis and Chromatography Group
María Rosa Becerra Arias (Associate Professor) ReID ORCID
Rosa Lebrón Aguilar (Assistant Professor) ReID ORCID SCOPUS
José María Santiuste Bermejo (Assistant Professor)
Summary
The Group studies the reactivity and reaction
mechanisms of the intermediate species of
Si, Ge, and Sn known as heavy carbenes
because of their high technological, industrial
and theoretical interest. Absolute rates of the
reactions of heavy carbenes are obtained by
direct, time-resolved kinetic experiments using
laser flash photolysis. Analysis of reaction
products and stable intermediates by gas
chromatography coupled to mass spectrometry
(GC-MS) allows us to determine reaction
mechanisms. Since chromatographic resolution
of these complex mixtures is difficult, the Group
investigates the use of ionic liquids (ILs) as new
GC stationary phases and also the development
of the necessary technology for the preparation
of capillary columns using ILs. At this point,
the information provided by inverse gas
chromatography (IGC) on molecular interactions
and solvation properties is essential, as it allows
the extension of the application of ILs, not only
in the development of analysis methods in
different areas (environment, food, etc.), but
also in organic synthesis or extraction process,
among others.
Strategic Aims
• New reaction kinetic studies of silicon and germanium containing heavy carbenes of interest
in the materials industry.
• Development and characterization of new stationary phases for gas chromatography based
on ionic liquids.
• Determination of chromatographic and thermodynamic parameters by gas chromatography.
• Development of advanced analytical methods by chromatography and mass spectrometry.
42
Chemical Reactivity
Results
Reactivity of heavy carbenes of Si
and Ge with sulfur dioxide
Heavy carbenes are divalent compounds of
Group 14. Heavy methylenes are specifically the
hydrides of heavy carbenes. Heavy methylenes
such as silylene (SiH2) and germylene (GeH2)
are of importance as key intermediates in the
processes of electronic materials manufacture.
Other heavy carbenes are intermediates involved
in ceramics production.
Sulfur dioxide is an intriguing molecule. It is
important in the environment, as a cause of
acid rain, but also of interest in combustion as
a reactive gaseous component species. There is
even still debate about the nature of its bonding.
Our interest arises for two reasons. First, as a
part of wider study of reactive heavy carbenes
with gaseous small molecules, and secondly
and more specifically, because we had already
studied the reaction of silylene (SiH2) with
carbon dioxide, and we wanted to compare it
with SiH2 + SO2.
Kinetic studies
Our method is Laser Flash Photolysis, using
Excimer photolysis at 193 nm of a suitable
precursor to create SiH2 or GeH2 and an Argon
Ion pumped dye laser to monitor the SiH2 or
GeH2 species on a nanosecond timescale. This
gives the desired gas-phase kinetic data for
reaction with the substrate over a pressure
range of 1-100 Torr and temperature range of
300 -600 K.
Our results show that the reaction of silylene
with sulfur dioxide in the gas phase is a fast
process with no energy barrier, occurring at 71%
of the maximum (collision) rate at 298 K. The
rate coefficients show no pressure dependence
and the reaction has a negative activation energy
of -3.5 kJ mol-1.
The G3 calculated potential energy surface
shows the presence of two stable low-energy
cyclic molecules, but the lack of pressure
dependence, predicted by RRKM theory, shows
that these are not the end products. The most
suitable candidates for these are H2SiO + 3SO.
The reaction contrasts strongly with that of
SiH2 + CO2, which is slow and has a positive
activation energy. A comparison of the potential
energy surfaces indicates that the π-bond in
SO2 is weaker than that in CO2 thus making the
initial addition easier.
Our further study of the reaction of germylene
with sulfur dioxide in the gas phase shows
similar kinetics, viz. a fast process with
no energy barrier, occurring at 19% of the
maximum (collision) rate at 298K. The rate
coefficients are a little slower but again show
no pressure dependence. The reaction has a
negative activation energy of -4.6 kJ mol-1. The
G3B3 calculated potential energy surface shows
significant differences with that of SiH2 + SO2.
Figure 1. Reaction mechanism of SiH2 with SO2
43
Chemical Reactivity
In particular, it shows the existence of a low
energy pathway leading to the unexpected and,
as yet, unsynthesised cyclo-GeO2S molecule via
H2 elimination. Another novel and surprisingly
stable species, Ge(OH)2··S, a cyclic fivemembered ring comprising an S atom stabilised
by dihydroxygermylene, was found on this
surface, although it appears not to be involved
in the mechanism.
The heavy methylenes SiH2 and GeH2 are more
reactive than most atmospheric intermediates
and free radicals, and their chemistry, as revealed
by these studies, is complex and diverse.
Figure 2. Potential Energy surface (low enthalpy pathways) for GeH2+ SO2.
44
Chemical Reactivity
Anomalous
behavior
of
the
isothermal retention indices of
alicyclic compounds
Isothermal Kováts retention indices (I) are
essentially used in gas chromatography (GC)
for identification purposes, but they are
also useful in characterization of stationary
phases (SPs) and for studying structural and
physicochemical properties of both the analyte
and the SP. Therefore, it is very important to
have very accurate I values. Several years ago,
our group developed a method for calculating I
values with greater accuracy than the classical
methods. Since then, we have been contributing
to increase the isothermal retention index data
in the NIST database.
During these two years, 670 I values of solutes
belonging to 9 different chemical functions
on a poly(100% dimethylsiloxane) SP have
been obtained. For some solutes, they are
reported for the first time on capillary columns.
Moreover, we have found that I values increased
with increasing column temperature, with the
exception of the linear alcohols and the esters,
which decreased with increasing temperature,
and of cyclobutanol, 2-butanone, 2-pentanone,
1-butylamine and 1-pentylamine that showed a
well-defined minimum in the 358–377 K range.
On the other hand, linear relationships were
found between I values and the number of
carbon atoms (z) in the solute. A slope value
around 100 was obtained, except for the alicyclic
compounds, for which higher slope values were
obtained. Moreover, a significant increase of the
slopes with increasing temperature was also
noticed for these compounds. This anomalous
behavior was explained on basis of their
structures. Alicyclic compounds have a larger
surface area able to interact with the SP than the
linear ones. The enlargement of the cycloalkane
ring by the addition of a methylene group leads to
a higher increase of its surface area with respect
to that of the linear homologue. Consequently,
the retention index increases considerably with
the increasing cycle size. Furthermore, they are
more affected by the easier solute insertion in
the SP as temperature increases, due to their
higher stiffness and surface area, this being
more evident with increasing cycle size. As a
result, for alicyclic solutes the slope of the I vs. z
plot becomes steeper as temperature increases.
Finally, from the data of this work we have
initiated the study of the relationship between I
and thermodynamic magnitudes.
Figure 3. Slopes (m) of I vs. z plots for different chemical families:
() 423 K and () 333–413 K; () y ( ) taken from the literature.
45
Chemical Reactivity
Ionic liquids as stationary phases
for gas chromatography
Over the past decade, ionic liquids (ILs) have
generated great interest because of their unique
and tunable physicochemical properties and
their versatility for various applications. They are
organic salts with melting points below 100 °C
that typically possess negligible vapor pressure,
high viscosity, good thermal stability and wide
liquid ranges. All these properties make them
ideal candidates as SPs for GC. In order to have
a more specific idea of their potential, we have
approached the problem from two different
perspectives:
Characterization of the
columns based on ILs
commercial
To date, only seven different ILs have been
used to prepare commercial capillary columns.
During these two years, in collaboration with the
group of Dr. Mª Luz Sanz (IQOG, CSIC), we have
carried out their characterization by means of
the solvation parameter model (SPM), in order to
better understand their retention mechanisms.
They can be considered moderately hydrogenbond acid and highly cohesive SPs, on which
the dominant contributions to retention are
the dipolar-type and hydrogen-bond base
interactions, with barely significant π-π and
n-π interactions. One of the most outstanding
characteristics found for these ILs when
compared with other non-ionic SPs, is that they
are hydrogen-bond acids. This acidity, along
with their high polarity, confers on them unique
separation properties, which clearly enhances
the separation capacity of GC.
Evaluation of different ILs as new SPs
for capillary columns
The experimental set-up for fused silica
capillary
column
preparation
developed
in the previous biennium has allowed
us to prepare and characterize columns
with
1-allyl-3-methylimidazolium
bis(trifluoromethanesulfonyl)amide
([AMIM]
[NTf2]) ionic liquid. The columns obtained
showed high polarity, acceptable efficiency and
maximum allowable operating temperatures of
220 °C, which makes them very promising for
further improvements. According to the SPM
results, dipolar-type and hydrogen-bond base
interactions were the dominant contributions
to retention, while π-type interactions were
barely significant. Moreover, [AMIM][NTf2] is
a moderately hydrogen-bond acid and very
cohesive SP. As a result of the different retention
mechanisms involved, the new columns are
highly versatile and have a noteworthy capacity
to resolve complex mixtures. Thus, some of
these columns have been used to develop
a fast analytical method to control the PET
(polyethylene terephthalate) manufacturing
process.
Figure 4. Principal component analysis for the studied ILs and the most common SPs
used in capillary GC: (1) Trifluoropropyl, (2) phenyl and (3) cyanopropyl siloxanes, and (4)
poly(ethylene glycols).
46
Chemical Reactivity
Characterization
by
LC-MSn
of
sialylated
oligosaccharides
from
ovine
and
caprine
caseinomacropeptide
Caseinomacropeptide (CMP), one of the major
components of sweet whey, is produced by
enzymatic cleavage of κ-casein during the primary
stage of cheese making or during digestion
in the stomach. The term CMP designates
a heterogeneous group of polypeptides due
to genetic variance and post-translational
modifications, such as phosphorylation and
glycosylation. Isolation and characterization
of oligosaccharides from CMP are important in
understanding their biological and functional
properties. However, it is difficult to achieve
this goal, due to the high degree of isomerism
present in these types of compounds.
In this biennium, we have developed a new
methodology for the detection and identification
of sialylated oligosaccharides from ovine and
caprine CMP, based on graphitized carbon
liquid chromatography-(ion trap) tandem mass
spectrometry (LC-MSn). The optimized procedure
allowed an exhaustive characterization of
O-glycans of ovine and caprine CMP, four
trisaccharides and four tetrasaccharides to be
identified. The chromatographic method resolved
linear and branched trisaccharides, as well as
oligosaccharides of different polymerization
degree, but not those having the same structure
and differing only in the NeuAc or NeuGc
units. However, results previously obtained
by our group allowed a complete elucidation
of the oligosaccharides studied even in case
of coelution, using the information provided
by their characteristics MSn spectra. Thus, the
methodology developed using an ion trap-type
mass analyzer could be used for unequivocal
identification of short O-glycan oligosaccharides
in other glycoproteins.
Figure 5. Chemical structures of O-glycans identified in ovine and caprine milk.
47
Chemical Reactivity
Proanthocyanidins profile in plants
by DI-ESI MS
Proanthocyanidins (PA) or condensed tannins
are polymers of flavan-3-ol that are widely
distributed in the plant kingdom and are
among the most abundant polyphenols in our
diet. Besides their participation in food quality
attributes such as astringency, bitterness,
aroma and color formation, PA consumption
has
been
associated
with
numerous
health benefits due their antioxidant, anticarcinogenic, cardioprotective, antimicrobial
and neuroprotective activities. Because of that,
they are considered as functional ingredients in
botanical and nutritional supplements. However,
due to their structural diversity and complexity,
the qualitative and quantitative analysis of PA is
a difficult task.
Several years ago, we initiated a study in order
to achieve a sound methodology to quantify
and identify PA in different matrices by MS.
Reproducible mass spectra of proanthocyanidins
in several nut skin extracts were obtained by
direct injection-electrospray ionization mass
spectrometry (DI-ESI MS), showing prevalence
of monocharged ions, with no significant
degradation, very good resolution and mass
ranges up to 5000 u.
During this biennium, in collaboration with the
group of Dr. Begoña Bartolomé (CIAL, CSIC),
cranberry extracts have been successfully
analyzed by DI-ESI MS. These results are
significant because cranberry products are widely
recommended in traditional American medicine
for the prevention of urinary tract infections
(UTI), and in recent years their popularity has
considerably increased in the European market.
With the aim of getting further insight into the
establishment of the PA protective action against
UTI, we have begun to analyze their content in
incubations of PA with bacteria and in mouse
feces after intake of cranberry extracts.
Figure 6. Direct injection mass spectrum of a cranberry extract.
48
Chemical Reactivity
Publications
Casal, E.; Lebrón-Aguilar, R.; Y. ChuanLee, Y.; Noboru, T.; Quintanilla-López,
J.E. (2013). Identification of sialylated
oligosaccharides derived from ovine and
caprine caseinomacropeptide by graphitized
carbon liquid chromatography-electrospray
ionization ion trap tandem mass spectrometry.
Food Anal. Methods 6, 814-825.
Becerra R.; Cannady J.P.; Walsh R. (2013).
Time-resolved gas-phase kinetic studies
of the reaction of dimethylsilylene with
triethylsilane-1-d: kinetic isotopic effect for
the Si-H insertion process. Phys. Chem.
Chem. Phys. 15, 5530-5538.
Becerra R.; Cannady J.P.; Goldberg N.;
Walsh R. (2013). Reaction of silylene with
sulfur dioxide: some gas-phase kinetic and
theoretical studies. Phys. Chem. Chem.
Phys. 15, 14748-14760.
Rodríguez-Sánchez, S.; Galindo-Iranzo, P.;
Soria, A.C.; Sanz, M.L.; Quintanilla-López, J.E.;
Lebrón-Aguilar, R. (2014). Characterization by
the solvation parameter model of the retention
properties of commercial ionic liquid columns
for gas chromatography. J. Chromatogr. A
1326, 96-102.
Santiuste, J.M.; Quintanilla-López, J.E.;
Becerra, R.; Lebrón-Aguilar, R. (2014). On
the influence of column temperature on the
isothermal retention indices of structurally
different solutes on a poly(dimethylsiloxane)
capillary column. J. Chromatogr. A 1365,
204-211.
Becerra R.; Cannady J.P.; Walsh R. (2014).
Reaction of germylene with sulphur dioxide:
gas-phase kinetic and theoretical studies.
Organometallics 33, 6493-6503.
49
Chemical Reactivity
COMPETITIVE FUNDING
Ministry for Science and Innovation
TitleReference
Begoña Bartolomé Sualdea
Proantocianidinas de tipo A: Estudio de su metabolismo por la microbiota
intestinal y acción protectora frente a infecciones
del tracto urinario
AGL2010-17499
Regional Government of Madrid
TitleReference
Mª José González Carlos
Metodologías analíticas innovadoras para el control de la calidad y la seguridad
de los alimentos
S2009/AGR-1464
Mª Luisa Marina Alegre
Estrategias avanzadas para la mejora y el control de la calidad y la seguridad
S2013/ABI-3028
Royal Society of Chemistry (RSC)
TitleReference
Rosa Becerra Arias
Kinetic studies of the simplest Criegee intermediate
50
Chemical Reactivity
Atmospheric Chemistry and Climate Group
Alfonso Saiz-López (Associate Professor) ReID
Non-tenured scientists
Carlos Alberto Cuevas Rodríguez (from 03/2013)
Rafael Pedro Fernández Cullen (03/2013 - 12/2013)
Cristina Prados Román (03/2013 - 09/2014)
Xavier Rodriguez Lloveras (06/2014 - 12/2014)
Technical Staff
Arturo Alonso de León (03/2013 - 08/2014)
Mónica Anguas Ballesteros (from 11/2014)
Chiara Cerruti (03/2013 - 10/2014)
Miguel Fernández Sánchez (03/2013 - 10/2014)
51
Chemical Reactivity
Summary
The Atmospheric Chemistry and Climate group
(AC2) is a newly created research group
within CSIC´s Institute of Physical Chemistry
Rocasolano (IQFR). AC2 research efforts are
directed at studying the role of atmospheric
composition and chemistry in the climate system.
Within this scientific framework, AC2 provides
an integrated research approach combining
atmospheric measurements (satellite- and
ground-based), modelling (microphysical to
global chemistry-climate) and laboratory studies
(photochemistry).
Strategic Aims
• The goals are to explore the interactions between anthropogenic and natural emissions, the
chemical and physical climate system, and the biosphere, within a changing climate context.
52
Chemical Reactivity
Results
We have implemented a state-of-the-art scheme
of the atmospheric chemistry of bromine and
iodine in the 3D chemistry climate model CAMCHEM (Community Atmospheric Model with
Chemistry, version 4.0), included into the CESM
framework (Community Earth System Model,
version 1.1.1).
Using this model we have calculated an annual
average stratospheric injection of total bromine
due to very short-lived (VSL) sources of about
5 pptv (parts per trillion by volume), ∼3 pptv
entering the stratosphere as product gases
(PGVSL) and ∼2 pptv as source gases (GVSL).
The geographic distribution and partitioning
of VSL bromine within the tropical tropopause
layer (TTL), and its consequent stratospheric
injection, indicate that atomic Br should be the
dominant inorganic species in large regions of the
tropical tropopause layer (TTL) during daytime,
due to the low ozone and cold conditions of this
region. We propose the existence of a “tropical
ring of atomic bromine” located approximately
between 15 and 19 km and between 30º N and
30º S. Daytime Br/BrO ratios of up to ~4 are
predicted within this inhomogeneous ring in
regions of highly convective transport, such as
the tropical Western Pacific.
The ranges of inorganic iodine loading,
partitioning and impact in the troposphere
have also been studied. Our results show that
the most abundant daytime iodine species
throughout the middle to upper troposphere is
atomic iodine, with an annual average tropical
abundance of (0.15–0.55) pptv. We propose the
existence of a “tropical ring of atomic iodine” that
peaks in the tropical upper troposphere (∼11–14
km) at the equator and extends to the subtropics (30ºN–30ºS). Annual average daytime
I/IO ratios larger than 3 are modelled within
the tropics, reaching ratios up to ∼20 during
vigorous uplift events within strong convective
regions. We calculate that the integrated
contribution of catalytic iodine reactions to the
total rate of tropospheric ozone loss is 25 times
larger than the combined bromine and chlorine
cycles. Iodine loss represents an upper limit of
approximately 27, 14 and 27% of the tropical
annual ozone loss for the marine boundary
layer (MBL), free troposphere (FT) and upper
troposphere (UT), respectively, while the lower
limit throughout the tropical troposphere is ~9
%. Our results indicate that iodine is the second
strongest ozone-depleting family throughout the
global marine UT and in the tropical MBL (SaizLopez et al., 2014; Fernandez et al., 2014).
Figure 1. “Tropical rings of atomic halogens”: daytime levels of atomic Br and I increase
significantly in the upper tropical troposphere until they become the dominant species for each
halogen family, surpassing the abundance of the commonly targeted BrO and IO radicals. The
main drivers are the low ozone mixing ratios (O3 < 100 ppbv) and cold temperatures (T <
200K) that slows down the otherwise dominant Br/I + O3 → BrO/IO reaction. The tropical rings
circle the tropics following the sun at different heights (11−15 km for iodine and 15−19 km for
bromine) due to their distinctive photochemistry.
53
Chemical Reactivity
Naturally emitted from the oceans, iodine
compounds efficiently destroy atmospheric
ozone and reduce its positive radiative forcing
effects in the troposphere. Emissions of inorganic
iodine have been experimentally shown to
depend on the deposition to the oceans of
tropospheric ozone, whose concentrations have
significantly increased since 1850 as a result of
human activities. We have used the chemistryclimate model CAMCHEM to quantify the current
ocean emissions of inorganic iodine and assess
the impact that the anthropogenic increase of
tropospheric ozone has had on the natural cycle
of iodine in the marine environment since preindustrial times. Our results indicate that the
human-driven enhancement of tropospheric
ozone has doubled the oceanic inorganic iodine
emissions following the reaction of ozone with
iodide at the sea surface. The consequent
build-up of atmospheric iodine, with maximum
enhancements of up to 70% with respect to
preindustrial times in continental pollution
outflow regions, has in turn accelerated the
ozone chemical loss over the oceans with strong
spatial patterns. We suggest that this oceanatmosphere interaction represents a negative
geochemical feedback loop by which current
ocean emissions of iodine act as a natural buffer
for ozone pollution and its radiative forcing in
the global marine environment. (Atmos. Chem.
Phys., 15, 2215-2224, 2015).
Figure 2. Geochemical feedback mechanism. The anthropogenic increase in tropospheric
ozone during the last two centuries (20-55%, Myhre et al., 2013) has led to an amplification
of the natural cycle of iodine emissions since pre-industrial times (PI cycle in yellow). This has
consequently decreased the lifetime of ozone in the marine atmosphere and its associated
RF, thus closing a negative feedback loop and presenting the ocean emissions of iodine as a
natural mitigating factor for anthropogenic RF in the marine environment (PD cycle in red).
54
Chemical Reactivity
We have developed the first global data set
of iodine oxide (IO) measurements in the
open marine boundary layer (MBL), using a
DOAS instruments during the Malaspina 2010
circumnavigation. Results show IO mixing
ratios ranging from 0.4 to 1 pmol mol-1 (30%
uncertainty) and, complemented with additional
field campaigns, this data set confirms through
observations the ubiquitous presence of
reactive iodine chemistry in the global marine
environment. We then use the global model
CAMCHEM including organic (CH3I, CH2ICl, CH2I2
and CH2IBr) and inorganic (HOI and I2) iodine
ocean emissions to investigate the contribution
of the different iodine source gases to the
budget of IO in the global MBL. In agreement
with previous estimates, our results indicate
that, globally averaged, the abiotic precursors
contribute about 75% to the IO budget. However,
this work reveals a strong geographical pattern
in the contribution of organic vs. inorganic
precursors to reactive iodine in the global MBL.
(Atmos. Chem. Phys., 15, 583-593, 2015).
We have studied the evolution of tropospheric
nitrogen dioxide (NO2) over Spain, focusing
on the densely populated cities of Barcelona,
Bilbao, Madrid, Sevilla and Valencia, during
17 years, from 1996 to 2012. This data series
combines observations from in-situ air quality
monitoring networks and the satellite-based
instruments GOME and SCIAMACHY. The results
in these five cities show a smooth decrease in
the NO2 concentrations of ∼2% per year in the
period 1996–2008, due to the implementation of
emissions control environmental legislation, and
a more abrupt descend of ~7% per year from
2008 to 2012 as a consequence of the economic
recession. In the whole Spanish territory the
NO2 levels have decreased by ∼22% from 1996
to 2012 (Cuevas et al., 2014).
Figure 3. Iodine oxide observations in the global marine boundary layer. IO mixing ratios are
shown for five different field campaigns: Malaspina (this work), CHARLEX (Gómez Martín et
al., 2013a), TransBrom (Großmann et al., 2013), HaloCAST-P (Mahajan et al., 2012) and Cape
Verde (Read et al., 2008; Mahajan et al., 2010), as well as also for the MBL measurements
reported by Dix et al. (2013) during one research flight.
55
Chemical Reactivity
Figure 4. Averaged tropospheric NO2 vertical column densities for different seasons during
1996 using the GOME resolution-corrected database (a, c and e), and 2011/2012 using
SCIAMACHY data (b, d, f). Top: annual averages. Middle: summer (Jun-Jul-Aug) averages.
Bottom: winter (Dec-Jan-Feb) averages.
Mercury is a contaminant of global concern. It
is transported in the atmosphere primarily as
gaseous elemental mercury, but its reactivity
and deposition to the surface environment,
through which it enters the aquatic food
chain, is greatly enhanced following oxidation.
Measurements and modelling studies of oxidised
mercury in the polar to sub-tropical marine
boundary layer (MBL) have suggested that
photolytically produced bromine atoms are the
56
Chemical Reactivity
primary oxidant of mercury. In this work we
report year-round measurements of elemental
and oxidised mercury, along with ozone,
halogen oxides (IO and BrO) and nitrogen oxides
(NO2), in the MBL over the Galápagos Islands
in the equatorial Pacific. Elemental mercury
concentration remained low throughout the year,
while higher than expected levels of oxidised
mercury occurred around midday. Our results
show that the production of oxidised mercury
in the tropical MBL cannot be accounted for by
bromine oxidation only, or by the inclusion of
ozone and hydroxyl. As a two-step oxidation
mechanism, where the HgBr intermediate is
further oxidised to Hg(II), depends critically on
the stability of HgBr, an additional oxidant is
needed to react with HgBr to explain more than
50% of the observed oxidised mercury. Based
on best available thermodynamic data, we show
that atomic iodine, NO2, or HO2 could all play
the potential role of the missing oxidant, though
their relative importance cannot be determined
explicitly at this time due to the uncertainties
associated with mercury oxidation kinetics. We
conclude that the key pathway that significantly
enhances atmospheric mercury oxidation and
deposition to the tropical oceans is missing
from the current understanding of atmospheric
mercury oxidation (Wang et al., 2014).
Figure 5. Comparison of the average daily profile of reactive gaseous mercury (RGM) during
October (grey area indicates the standard deviation of the data) with simulated profiles
obtained by two different modelling approaches. (a) Modelled results from the original
chemistry scheme according to Goodsite et al. (2004) and Holmes et al. (2009) under four
different scenarios. (b) Modelled results using an updated chemistry scheme according to
Goodsite et al. (2012) and Dibble et al. (2013).
57
Chemical Reactivity
Publications
Gómez Martín, J.C.; Mahajan, A.; Hay, T.D.;
Prados-Román, C.; Ordóñez, C.; McDonald,
S.M.; Plane, J.M.C.; Sorribas, M.; Gil, M.;
Paredes Mora, F.; Agama Reyes, M.V.; Oram,
D.E.; Leedham, E.; Saiz-Lopez, A. (2013).
Iodine chemistry in the eastern Pacific marine
boundary layer. JGR Atm. 118, 1-1454.
Gálvez, O.; Gómez Martin, J.C.; Gómez,
P.C.; Saiz-Lopez, A.; Palacios, F. (2013). A
theoretical study on the formation of iodine
oxides aggregates and monohydrates. Phys.
Chem. Chem. Phys. 15, 15572.
Hossaini, R.; Mantle, H.; Chipperfield, M.P.;
Montzka, S.A. ; Hamer, P.; Ziska, F.; Quack,
B.; Krüger, K.; Tegtmeier, S.; Atlas, E.;
Sala, S.; Engel, A.; Bönisch, H.; Keber, T.;
Oram, D.; Mills, G.; Ordoñez, C.; SaizLopez,
A.; Warnick, N.; Liang, Q.; Feng, W.; Moore,
F.; Miller, B.R.; Marécal, V.; Richards, N.A.;
Dorf, M.; Pfeilsticker, K. (2013). Evaluating
global emission inventories of biogenic
bromocarbons. Atmos. Chem. Phys. 13,
11819-11838.
Wang, F.; Saiz-Lopez, A.; Mahajan, A. S.;
Gómez Martín, J. C.; Armstrong, D.; Lemes,
M.; Hay, T.; Prados-Roman, C. (2014).
Enhanced production of oxidized mercury
over the tropical Pacific Ocean: a key
missing oxidation pathway. Atmos. Chem.
Phys. 14, 1323-1335.
Lawler, M. J.; Mahajan, A. S.; Saiz-Lopez,
A.; Saltzman, E. S. (2014). Observations of
I2 at a remote marine site. Atmos. Chem.
Phys. 14, 2669-2678.
Mahajan, A.S.; Prados-Roman, C.; Hay,
T.D.; Lampel, J.; Pöhler,D.; Grossmann, K.;
Tschritter,J.; Friess, U.; Platt, U.; Johnston,
P.; Kreher, K.; Wittrock ,F.; Burrows, J.P.;
Plane, J.M.C.; Saiz-Lopez, A. (2014). Glyoxal
observations in the marine boundary layer.
JGR. Atmos. 119, 6160-6169.
MacDonald, S.M.; Gómez Martín, J.C.;
Chance, R.; Warriner, S.; SaizLopez, A.;
Carpenter, L.J.; Plane, J.M.C. (2014). A
laboratory characterization of inorganic iodine
emissions from the sea surface: dependence
on oceanic variables and parameterization for
global modelling. Atmos. Chem. Phys. 14,
5841-5852.
Cuevas, C.A.; Notario, A.;
Adame, J.A.;
Hilboll, A.; Richter, A.; Burrows, J.P.; SaizLopez, A. (2014). Evolution of NO2 levels in
Spain from 1996 to 2012. Sci. Rep. 4, 5887.
Fernandez, R.P; Salawitch, R.J.; Kinnison,
D.E; Lamarque, J.-F.; Saiz-Lopez, A. (2014).
Bromine partitioning in the tropical tropopause
layer: implications for stratospheric injection.
Atmos. Chem. Phys. 14, 13391-13410.
Saiz-Lopez, A.; Fernandez, R.P.; Ordoñez, C.;
Kinnison, D.E.; Gómez Martín, J.C.; Lamarque,
J.-F.; Tilmes. S. (2014). Iodine chemistry in the
troposphere and its effect on ozone. Atmos.
Chem. Phys. 14, 13119-13143.
Boxe, C.S.; Francisco, J.S.; Shia, R.-L.; Yung,
Y.L.; Nair, H.; Liang, M.C; Saiz-Lopez, A.
(2014). New insights into martian atmospheric
chemistry. Icarus 242, 97-104.
Garçon, V.C.; Bell, T.G.; Wallace, D.; Arnold,
S.R.; Baker, A.; Bakker, D.C.E.; Bange, H.W.;
Bates, N.R.; Bopp, L.; Boutin, J.; Boyd, P.W.;
Bracher, A.; Burrows, J.P.; Carpenter, L.J.;
de Leeuw, G.; Fennel, K.; Font, J.; Friedrich,
T.; Garbe, C.S.; Gruber, N.; Jaeglé, L.; Lana,
A.; Lee, J.D; Liss, P.S.; Miller, L.A.; Olgun,
N.; Olsen, A.; Pfeil, B.; Quack, B.; Read,
K.A.; Reul, N.; Rödenbeck, C.; Rohekar, S.S.;
SaizLopez, A.; Saltzman, E.S.; Schneising,
O.; Schuster, U.; Seferia, R.; Steinhoff,
S.; Le Traon, P.Y.; Ziska, F. (2014) OceanAtmosphere Interactions of Gases & Particles,
2014, p247-306, 60p. Publisher: Springer
Science & Business Media B.V.
58
Chemical Reactivity
COMPETITIVE FUNDING
MINECO
TitleReference
Alfonso Saiz López
FASE C/D del instrumento Ultraviolet and Visible Atmospheric Sounder (UVAS) en
SEOSAT/INGENIO
AYA2011-30475
INTA
TitleReference
Alfonso Saiz López
Atmospheric MInor Species relevant to the Ozone
Chemistry at both sides of the subtropical jet.
AMISOC
Comunidad de Madrid
TitleReference
Alfonso Saiz López
Tecnologías innovadoras para la evaluación y mejora de la calidad del aire urbano
TECNAIR
EU
TitleReference
Alfonso Saiz López
Quality Assurance for Essential Climate Variables
QA4ECV
Aarhus University
TitleReference
Alfonso Saiz López
DOAS measurements of Halogen oxides at Station DOASGREEN
Nord (Greenland)
59
Chemical Reactivity
Department of Biological Physical
Chemistry
Memoria 2013/2014 Department of Structure, Energy and
61
Chemical Reactivity
Introduction
http://qfbio.iqfr.csic.es
The research experience in our research
Department covers the fields of Biochemistry,
Molecular
Biology,
Structural
Biology,
Biophysics, Glycobiology, Bioinformatics and
Biothermodynamics. The objective of our
ongoing work is to understand the physicalchemical bases governing the structure,
stability, dynamics and interactions of different
biological molecules such as peptides,
proteins, nucleic acids and carbohydrates.
This investigation is conducted on systems
with different levels of complexity, ranging
from isolated molecules to macromolecular
assemblies,
membrane
mimetics,
cells
and tissues. Many of these systems have
biomedical, pharmacological or biotechnical
importance.
We determine the structure and stability
of nucleic acids and their complexes with
proteins. The final aim is to characterise their
relationship with the mechanisms of gen
regulation at the transcriptional and posttranscriptional levels. We are also interested
in
the biophysical
characterization of
intrinsically disordered proteins, domains or
protein fragments; and we are studying model
systems in which this feature is essential for
the biological function.
The Department also carries out research
based on structural bioinformatics, and we
are actively involved in the development of
novel techniques for the simulation, analysis
and modelling of large biomolecular systems.
We also study processes involved in
the assembly and functional properties
amyloids, the broad aim of which is to
understand pathologies related to aberrant
conformations, neurodegenerative disease,
and in general, the process of aging. We also
study the role of carbohydrates as recognition
signals, their binding to ligands, and the
structural organization of protein receptors for
carbohydrate recognition. Other systems that
we study include choline receptors, murein
hydrolases, pneumococcal virulence factors
and various allergens and toxins.
We have extensive experience in studying the
mechanisms of protein folding and the design
of peptides with a defined structure. Our
work has contributed towards establishing
structure-function relationships in proteins
and protein-inhibitor complexes implicated in,
for example, angiogenesis, immune response,
and antiviral and antimicrobial activity.
Moreover, our research efforts have also
been directed towards the determination
of the structural organization and stability
of membrane protein complexes, how the
associated interactions alter the physical
properties of cell membranes, and the
mechanisms of action of anesthetics,
anticancer and antiparasite drugs.
Our Department is also actively involved in
research aimed at developing methodology
necessary for i) resolving problems related
to
molecular
heterogeneity
(isoforms,
modifications
and
conformational
heterogeneity), ii) enhancing the use
and applicability of NMR Spectroscopy
(development of new pulse sequences,
reduced
dimensionality
and
automatic
assignment methods), iii) resolving molecular
interactions
in
complex
environments
(fluorescence microspectroscopy or single
cell spectroscopy), or whole-cell approaches
(microarrays of design).
Experimental methods and equipment
The Department has all of the necessary
instrumentation for in-depth experimental
studies of biological samples. Laboratories
are well-equipped to carry out the basic
techniques employed in isolating, cloning,
expressing, purifying and concentrating
proteins and nucleic acids; and have
instrumentation necessary for their biophysical
characterisation: immunochemical analysis,
high-performance liquid chromatography,
analytical ultracentrigugation, light scattering
(MALLS), spectropolarimetry (CD), UV-visible
spectroscopy,
fluorescence
spectroscopy,
differential scanning calorimetry (DSC),
isothermal titration calorimetry (ITC). A
departmental microarray scanner, a manual
microarrayer and a scanner for microarrays
are also available.
The Department is also well-equipped with
instrumentation for advanced fluorescence
methods required in high-resolution temporal
(ps-ms) and spatial (mm-sub mm) studies
of biological systems at different levels of
organisation. We also have two high-field NMR
spectrometers, a 600 MHz instrument and an
800 MHz one, each equipped with a gradient
module and cryoprobe. All of the necessary
software has been installed for processing and
analyzing multidimensional NMR spectra, for
calculations of macromolecular structures in
solution, and for protein-protein and proteinligand docking analyses.
Scientific Report 2013/2014 Department of Biological
62
Physical Chemistry
Group Structure
NMR of Protein Structure, Dynamics and Interactions 64
Protein Bioconformatics and Assemblies
75
Structural Bioinformatics
80
Fluorescence and Molecular Biophysics
88
Protein Structure and Thermodynamics
96
NMR of Nucleic Acids
104
63
Physical Chemistry
Nmr of Protein, Structure, Dynamics and
Interactions Group
Doctoral students
Manuel Rico Sarompas
(Professor Ad honorem) († 01/12/2014)
Soraya Serrano Serrano (until 1/06/2014)
Jorge Santoro Said (Professor)
Hector Zamora Carreras
Santiago Martínez Lumbreras
(until 31/12/2013)
Marta Bruix Bayes
(Professor) ) ReID ORCID SCOPUS
María Ángeles Jiménez López
Subramanian Padmanabhan
(Associate Professor)
Juán Manuel Ortíz Guerrero
(until 31/12/2013)
Jesús Fernández Zapata (from 1/01/2014)
Technical Staff
José Manuel Pérez Cañadillas
(Assistant Professor) ReID ORCID
David Pantoja Uceda (TSE)
Miguel Angel Treviño Avellaneda
(TSE) ReID ORCID SCOPUS
Cristina López García (until 20/04/2014)
Mª Flor García Mayoral
(until 15/11/2013)
Luis de la Vega Serrada
Angélica Inés Partida Hanón
(from 1/09/2014) ORCID
Aránzazu Gallego García (from 1/10/2014)
64
Physical Chemistry
Summary
This group (http://rmn.iqfr.csic.es), reputed
nationally and internationally, is a pioneer
in Spain in the application of NMR to the
determination
of
the
three-dimensional
structure, dynamics and interactions of proteins
and peptides, whose knowledge is essential
for understanding the physicochemical bases
of their biological functions and the regulatory
mechanisms underlying their activities. Within
this broad field, we study the structure and
dynamics of a variety of biological systems. We
also concurrently work on implementing and
optimizing NMR methodology. This group and
that of the “NMR of Nucleic Acids”, together
manage and maintain the Manuel Rico NMR
Laboratory (http://rmn.iqfr.csic.es) that is
equipped with advanced NMR instrumentation.
The group has historically are been involved
in studies of protein-lipid interactions involved
in the cytotoxicity of specific ribonucleases
and actinoporins, the structural and dynamic
characterization of allergens and centrosomal
proteins, proteins participating in mRNP
formation and posttranscriptional control, and
the structures and interactions of proteins
regulating bacterial response to light. Peptide
design and protein folding, and the structural
characterization of intrinsically disordered, nonnative states and folding intermediates continue
to be subjects of study.
Strategic Aims
• Development of new NMR methodology for fast and highly efficient determination of threedimensional structures of biomacromolecules and their complexes.
• New methods to study intrinsically disordered proteins.
• Design of peptides with well defined conformations. Structure-activity relationships.
• Structural study of proteins of biomedical relevance: applications in cancer and allergy.
• Structural study of protein-nucleic acid complexes: applications in the regulation of gene
expression.
• Description of the molecular mechanisms of light sensing and response in bacteria and their
exploitation in optogenetic applications.
65
Physical Chemistry
Results
Implementation and optimization
of NMR methods
Design
and
structure-function
relationships in peptides
Traditional NMR methods are rather ineffective
with intrinsically disordered proteins (IDPs)
given their peculariarities. Consequently, there
is a considerable interest in the development
of experimental NMR techniques for IDPs. We
have developed pulse sequences that allow
the assignment of the NMR spectra of IDPs by
correlating the signals of two consecutive CO-N
in the protein sequence. Of growing importance
in NMR methodology is acquisition of spectra
with nonuniform sampling. In recent years
we have implemented and evaluated various
methods of non-uniform sampling. Selecting the
so-called Iterative soft thresholding method as
most suitable for our work, we have developed
over two dozen pulse sequences that enable an
~80% reduction in time for obtaining threedimensional spectra.
The determination of the structure of biologically
active peptides contributes to our understanding
of their biological function and paves the
way for the rational design of peptides with
pharmaceutical applications. Recent research
highlights from the group include the design and
structure determination of peptides that block
interactions between the protein VEGF and its
receptors, of cyclic peptides derived from αMSH,
of peptides corresponding to the choline binding
repeats present in pneumococcal proteins, and
of immunogenic peptides derived from the HIV1 gp41 protein, which plays an important role in
membrane fusion during viral entry to the host
cell, and also contains several linear epitopes.
Also ongoing are studies of peptide-lipid
interactions aimed at a better understanding
of the structure-activity relationships in
antimicrobial peptides.
Figure 1. NMR structure of peptide MPERp from gp41 in the presence of
hexafluoroisopropanol (left) and in dodecylphosphocholine micelles (right). The Trp side chains
belonging to 2F5 (in green) and 4E10 (in magenta) epitopes are displayed. The amino-end is
indicated by an “N”.
66
Physical Chemistry
Molecular
sensing
mechanisms
of
light
Our goal is to understand the molecular
mechanisms of light sensing and response in
bacteria. We combine high-resolution structural
and biophysical studies with functional analyses
(in collaboration with the Genetics group in the
University of Murcia) of several protein factors
that serve as receptors and transducers of the
light signal, or are specific or global regulators
of gene expression in the model bacterium,
Myxococcus xanthus. Many of the factors that
we study have turned out to be the prototypes
of novel and widespread protein families. Our
studies have led to high-resolution, structuralfunctional insights of photosensory transcriptional
factors that employ 5´-deoxyadenoylcobalamin
(coenzyme B12) as the chromophore to act as
a light-sensing allosteric switch, and how their
actions can be downregulated by a protein with
an SH3-domain topology that mimicks DNA. We
have also uncovered a large family of bacterial
RNA polymerase binding proteins with critical
roles in the expression of essential genes, or of
genes activated in response to specific stress
signals such as light.
Figure 2. Structure of the M. xanthus CdnL in ribbon representation. CdnL is a member of
the large CarD_CdnL_TRCF family of bacterial RNA polymerase binding proteins interaction
that has been shown to be essential for cell growth and survival and is implicated in rRNA
transcription in M. xanthus and in mycobacteria, like Mycobacterium tuberculosis. The
N-terminal, all-β (labeled) Tudor-like domain shown in cyan on the left is the RNA polymerase
interaction domain with side-chains of contact residues indicated. The all-helical C-terminal
domain resembles some TPR (tetratricopepetide) domains, and the residues indicated form a
solvent-accessible basic-hydrophobic patch crucial for function. The α-helices of these domains
are shown in red (α1), magenta (α2), yellow (α3), blue (α4) and green (α5).
67
Physical Chemistry
Structure
and
interactions
of
proteins involved in RNA metabolism
We continue research on several protein and
protein domains involved in the biogenesis of
different types of RNAs (mRNAs, snoRNAs,etc.).
We have assigned the NMR spectra of a 20 KDa
intrinsically disordered fragment of Tif4631
of the Pub1/Tif¡4631 system involved in the
nucleation of stress granules, and characterized
its molecular recognition features (MORFs).
Our published structure and RNA binding mode
of part of the CCCH-type zinc finger region of
Nab2, a critical factor for poly(A) tail length
control, reveal remarkable features like the
self recognition of the two histidine residues
coordinating the zinc ions in fingers 3 and 4
(see figure 3). We have also obtained results
for other systems including Gbp2/Hrb1, proteins
involved in THO/TREX recruitment to nascent
mRNA during transcription in collaborative work
with the Bertrand Seraphin group (IGBMC/
CNRS, France).
Figure 3. NMR structure of Nab2 zinc finger 3-4 tandem showing the atomic detail of the
hydrogen bond network between His 355 and His 386. The degree of protection of Hδ1 of
these histidine residues is such that build up observable correlation peaks with their attached
Nδ1 in the 1H-15N HSQC.
68
Physical Chemistry
Structure-function relationships in
Anisakis alergens
Understanding the function of biomolecules
requires not only know the isolated structures,
but also the interactions with other biomolecules.
We are studying the principal allergens of
Anisakis, at present one of the most important
food-borne allergies. Ani s 5 belongs to the SXP
/ RAL-2 family of exclusively nematode origin.
The function of this highly antigenic protein is
unknown. We have determined the structure of
the principal regions involved in IgE and IgG4
binding, the first-ever structure resolved for
an Anisakis allergen. Ani s 5 has the ability to
bind divalent metals, which may be important
for its function. The IgE /IgG4-binding regions
are located linearly along the surface of the
structure. The emerging structural data can help
in the future design of new diagnostic tests and
strategies for immunotherapy.
Figure 4. Ribbon representations of Ani s 5 with epitope mapping. A and B, Peptide segments
representing the minimum unit necessary for IgE/IgG4 recognition are colored in cyan (E1,
7-18), purple (E2, 19-24), hot pink (E3, 31-36), blue (E4, 40-48), yellow (E7, 79-90), red (E8,
91-102), green (E9, 97-116) and dark green (E11, 109-128). The overlapping region 110116 is colored in pale green. C and D, Peptide segments recognized simultaneously by three
different sera are colored in red (E5, 40-59), green (E6, 85-96) and cyan (E10, 103-122). Two
perspectives rotated 180º with respect to each other are shown in each panel.
69
Physical Chemistry
Structure
and
actinoporins
association
of
We continue to study actinoporin protein family
structure (of StnI) and association (of StnII) to
membranes in solution and at the cell surface.
A knowledge of these is fundamental for
understanding their hemolytic and toxic activity
through pore formation. Notably, our atomic
level description of the interaction of Stn I with
micelles provides insights into the initial stages
of pore formation by these proteins.
RNases of therapeutical interest
In line with that described in the previous
Annual Report, we have worked on elucidating
the structure and interactions of an Onconase
zymogen with significant therapeutic potential
(ONCFLG), as it can be selectively activated by
the HIV-1 protease. Using NMR as a tool, we
have conducted a comprehensive study and
determined the three-dimensional structure
of the native and activated zymogen, their
internal dynamics and conformational stability.
Structural and dynamic changes resulting from
zymogen activation by the HIV-1 protease,
allowed the description of the structureactivity relationships and the structural motifs
responsible for the high conformational stability,
which may be important from the standpoint of
its possible therapeutic action.
Figure 5. Representation of the final structures of the ONCFLG zimógeno. On the left,
superposition of the backbone atoms of the final 20 structures, the gray part represents the
16 residue insertion that blocks the active site. On the right, a ribbon representation of the
structures with the b-sheet regions in red.
70
Physical Chemistry
Interactions of centrosomal proteins
The centrosome is an organelle that plays a key
role in cell division, and whose dysfunction is
the origin of many diseases. Our studies have
proceeded in two ways. One involves the study
of fragments. Human centrosomal proteins are
rich in unstructured regions and coiled-coils, and
we showed that these features allow favourable
transitions between both conformations to
facilitate intermolecular complex formation.
Studies of the interactions of different
fragments of centrosomal proteins using NMR
and CD demonstrated that conformational
polymorphism modulated by intermolecular
contacts is a general property of these proteins.
These results might aid to improve oncologic
therapies directed to block cell division, and
hence to decrease proliferation and migration of
tumor cells.
Moreover, we participated in a study aimed at
understanding the interactions that regulate
the dynamic properties of microtubules and
their organization during mitosis. We have
characterized the molecular interaction between
TACC3 and chTOG, key proteins in the formation
of the intracellular scaffolding that enables and
supports cell division and perpetuation. Using
NMR we have identified the key residues crucial
for the molecular interaction. These results could
help in the improvement of cancer therapies
aimed at blocking the processes of cell division,
and thereby limit proliferation and expansion of
tumor cells.
71
Physical Chemistry
Publications
mechanism and immunogen design. J. Biol.
Chem. 289, 6565-6580.
Abellón-Ruiz, J., Bernal-Bernal, D., Abellán,
M., Fontes, M., Padmanabhan, S., Murillo,
F.J. and Elias-Arnanz, M. (2014). The CarD/
CarG regulatory complex is required for the
action of several members of the large set
of Myxococcus xanthus extracytoplasmic
function sigma factors. Environ. Microbiol.
16, 2475-2490.
Gallego-García, A., Mirassou, Y., GarcíaMoreno, D., Elias-Arnanz, M., Jiménez, M.A.
and Padmanabhan, S. (2014). Structural
insights into RNA polymerase recognition and
essential function of Myxococcus xanthus
CdnL. PLoS One 9, e108946.
García-Linares, S., Richmond, R., GarcíaMayoral, M.F., Bustamante, N., Bruix, M.,
Gavilanes, J.G. and Martínez-Del-Pozo, A.
(2014). The sea anemone actinoporin (ArgGly-Asp) conserved motif is involved in
maintaining the competent oligomerization
state of these pore-forming toxins. FEBS J.
281, 1465-1478.
García-Mayoral, M.F., Treviño, M.A., PérezPinar, T., Caballero, M.L., Knaute, T., Umpierrez,
A., Bruix, M. and Rodríguez-Pérez, R. (2014).
Relationships between IgE/IgG4 epitopes,
structure and function in Anisakis simplex
Ani s 5, a member of the SXP/RAL-2 protein
family. PLoS Negl. Trop. Dis. 8, e2735.
Jiménez, M.A. (2014). Design of Monomeric
Water-Soluble beta-Hairpin and beta-Sheet
Peptides. Methods Mol. Biol. 1216, 15-52.
Treviño, M.A., García-Mayoral, M.F., Jiménez,
M.A., Bastolla, U. and Bruix, M. (2014).
Emergence of structure through proteinprotein interactions and pH changes in dually
predicted coiled-coil and disordered regions
of centrosomal proteins. Biochim. Biophys.
Acta. 1844, 1808-1819.
Aguado-Llera, D., Hamidi, T., Domenech, R.,
Pantoja-Uceda, D., Gironella, M., Santoro,
J., Velázquez-Campoy, A., Neira, J.L. and
Iovanna, J.L. (2013). Deciphering the binding
between Nupr1 and MSL1 and their DNArepairing activity. PLoS One 8, e78101.
Ardá, A., Blasco, P., Varon Silva, D., Schubert,
V., Andre, S., Bruix, M., Canada, F.J., Gabius,
H.J., Unverzagt, C. and Jiménez-Barbero, J.
(2013). Molecular recognition of complex-type
biantennary N-glycans by protein receptors: a
three-dimensional view on epitope selection
by NMR. J. Am. Chem. Soc. 135, 2667-2675.
Bermel, W., Bruix, M., Felli, I.C., Kumar,
M.V.V., Pierattelli, R. and Serrano, S. (2013).
Improving the chemical shift dispersion of
multidimensional NMR spectra of intrinsically
disordered proteins. J. Biomol. NMR 55, 231237.
Callís, M., Serrano, S., Benito, A., Laurents,
D.V., Vilanova, M., Bruix, M. and Ribó, M.
(2013). Towards tricking a pathogen’s protease
into fighting infection: the 3D structure of a
stable circularly permuted onconase variant
cleavedby HIV-1 protease. PLoS One 8,
e54568.
Mortuza, G.B., Cavazza, T., García-Mayoral,
M.F., Hermida, D., Peset, I., Pedrero, J.G.,
Merino, N., Blanco, F.J., Lyngso, J., Bruix,
M., Pedersen, J.S., Vernos, I. and Montoya,
G. (2014). XTACC3-XMAP215 association
reveals an asymmetric interaction promoting
microtubule elongation. Nat. Commun. 5,
5072.
Diez, A.I., Ortiz-Guerrero, J.M., Ortega, A., EliasArnanz, M., Padmanabhan, S. and de la Torre,
J.G. (2013). Analytical ultracentrifugation
studies of oligomerization and DNA-binding
of TtCarH, a Thermus thermophilus coenzyme
B12-based photosensory regulator. Eur.
Biophys. J. 42, 463-476.
Pantoja-Uceda, D. and Santoro, J. (2014). New
13C-detected experiments for the assignment
of intrinsically disordered proteins. J. Biomol.
NMR 59, 43-50.
Diez-García, F., Pantoja-Uceda, D., Jiménez,
M.A., Chakrabartty, A. and Laurents, D.V.
(2013). Structure of a simplified beta-hairpin
and its ATP complex. Arch. Biochem.
Biophys. 537, 62-71.
Serrano, S., Araujo, A., Apellaniz, B., Bryson,
S., Carravilla, P., de la Arada, I., Huarte, N.,
Rujas, E., Pai, E.F., Arrondo, J.L., Domene,
C., Jiménez, M.A. and Nieva, J.L. (2014).
Structure and immunogenicity of a peptide
vaccine, including the complete HIV-1 gp41 2F5
epitope: implications for antibody recognition
Dos Santos, H.G., Abia, D., Janowski, R.,
Mortuza, G., Bertero, M.G., Boutin, M., Guarin,
N., Méndez-Giráldez, R., Nuñez, A., Pedrero,
J.G., Redondo, P., Sanz, M., Speroni, S.,
Teichert, F., Bruix, M., Carazo, J.M., González,
C., Reina, J., Valpuesta, J.M., Vernos, I.,
72
Physical Chemistry
Zabala, J.C., Montoya, G., Coll, M., Bastolla,
U. and Serrano, L. (2013). Structure and nonstructure of centrosomal proteins. PLoS One
8, e62633.
García-Aranda, M.I., González-López, S.,
Santiveri, C.M., Gagey-Eilstein, N., ReilleSeroussi, M., Martín-Martinez, M., Inguimbert,
N., Vidal, M., García-López, M.T., Jiménez,
M.A., González-Muñiz, R. and Pérez de Vega,
M.J. (2013). Helical peptides from VEGF and
Vammin hotspots for modulating the VEGFVEGFR interaction. Org. Biomol. Chem. 11,
1896-1905.
García-Heras, F., Abellón-Ruiz, J., Murillo,
F.J., Padmanabhan, S. and Elias-Arnanz, M.
(2013). High-mobility-group a-like CarD binds
to a DNA site optimized for affinity and position
and to RNA polymerase to regulate a lightinducible promoter in Myxococcus xanthus. J.
Bacteriol. 195, 378-388.
García-Linares, S., Castrillo, I., Bruix, M.,
Menéndez, M., Alegre-Cebollada, J., Martínezdel-Pozo, A. and Gavilanes, J.G. (2013).
Three-dimensional structure of the actinoporin
sticholysin I. Influence of long-distance
effects on protein function. Arch. Biochem.
Biophys. 532, 39-45.
García-Mayoral, M.F., Canales, A., Díaz, D.,
López-Prados, J., Moussaoui, M., de Paz, J.L.,
Angulo, J., Nieto, P.M., Jiménez-Barbero, J.,
Boix, E. and Bruix, M. (2013). Insights into
the glycosaminoglycan-mediated cytotoxic
mechanism of eosinophil cationic protein
revealed by NMR. ACS Chem. Biol. 8, 144151.
Martínez-Lumbreras, S., Santiveri, C.M.,
Mirassou, Y., Zorrilla, S. and Pérez-Cañadillas,
J.M. (2013). Two singular types of CCCH
tandem zinc finger in Nab2p contribute to
polyadenosine RNA recognition. Structure
21, 1800-1811.
Mirassou, Y., Elias-Arnanz, M., Padmanabhan,
S. and Jiménez, M.A. (2013). (1)H, (13)C
and (15)N assignments of CdnL, an essential
protein in Myxococcus xanthus. Biomol. NMR
Assign. 7, 51-55.
Morais, M., Oliveira, B.L., Correia, J.D., Oliveira,
M.C., Jiménez, M.A., Santos, I. and Raposinho,
P.D. (2013). Influence of the bifunctional
chelator on the pharmacokinetic properties of
99mTc(CO)3-labeled cyclic alpha-melanocyte
stimulating hormone analog. J. Med. Chem.
56, 1961-1973.
Pantoja-Uceda, D. and Santoro, J. (2013).
Direct correlation of consecutive C’-N groups
in proteins: a method for the assignment of
intrinsically disordered proteins. J. Biomol.
NMR 57, 57-63.
Pantoja-Uceda, D. and Santoro, J. (2013). A
suite of amino acid residue type classification
pulse sequences for 13C-detected NMR of
proteins. J. Magn. Reson. 234, 190-196.
San Sebastián, E., Zimmerman, T., Zubia, A.,
Vara, Y., Martin, E., Sirockin, F., Dejaegere,
A., Stote, R.H., López, X., Pantoja-Uceda, D.,
Valcárcel, M., Mendoza, L., Vidal-Vanaclocha,
F., Cossio, F.P. and Blanco, F.J. (2013).
Design, synthesis, and functional evaluation
of leukocyte function associated antigen-1
antagonists in early and late stages of cancer
development. J. Med. Chem. 56, 735-747.
Santiveri, C.M., García-Mayoral, M.F., PérezCañadillas, J.M. and Jiménez, M.A. (2013).
NMR structure note: PHD domain from death
inducer obliterator protein and its interaction
with H3K4me3. J. Biomol. NMR 56, 183-190.
Serrano, S., Callís, M., Vilanova, M., Benito, A.,
Laurents, D.V., Ribó, M. and Bruix, M. (2013).
(1)H, (13)C and (15)N resonance assignments
of the Onconase FL-G zymogen. Biomol. NMR
Assign. 7, 13-15.
73
Physical Chemistry
COMPETITIVE FUNDING
Ministerio de Economía y Competitividad
TitleReference
M.A. Jiménez
Bases estructurales del reconocimiento entre biomoléculas mediante RMN: proteínas y lípidos
CTQ2011-22514
M. Bruix
Red temática de estructura y función de proteínas
BFU2011-15733-E
J.M. Pérez Cañadillas
Papel de las interacciones proteína-proteína y proteina-RNA en la composición y dinámica
De ribonucleoproteínas (RNPs)
CTQ2011-26665
Comunidad de Madrid
TitleReference
M.A. Jiménez
Interactómica del centrosoma
S2010/BMD-2305
TitleReference
S. Padmanabhan Iyer
The light response regulatory network and connections to other regulatory networks in
the bacterium Myxococcus xanthus:
structural analyses
BFU2012-40184-CO2-02
74
Physical Chemistry
Bioconformatics and Assemblies Group
María Gasset Vega (Associate Professor) ReID ORCID SCOPUS
Doctoral students
Javier Martínez Férnandez (until 31/08/2014)
Technical Staff
Silvia Lisa Ferrer
Rosa Sánchez Hereros (until 31/12/2013 and 15/03/2014-15/12/2014)
75
Physical Chemistry
Summary
We aim to decipher the basic elements
forming the protein conformational disease
language and exploit them for therapeutic and
biotechnological purposes. For such purpose
we use molecular biology, cellular biology and
biophysical approaches and collaborate with the
groups of Prof. A. Aguzzi (UZ, Switzerland), Ilia
V. Baskakov (UM,USA), and V. Muñoz (IMDEACNB).
Strategic Aims
• To determine the celular basis of the cytotoxicity of intracelular protein aggregates relevant
to neurodegenerative disorders (CtmPrP).
• To unveil the basis of PrP amyloid polymorphism and its relation to self-propagation.
• To generalize amiloidogenesis to other pathogens following oral route exposition.
76
Physical Chemistry
Results
To determine the celular basis
of the cytotoxicity of intracelular
protein aggregates relevant to
neurodegenerative
disorders
(CtmPrP)
forming intracellular CtmPrP accumulative
forms occurs with enhanced ER stress markers
and high cell death. Using several modulators of
intracellular redox has permitted the finding of
PDI activity levels as key element for aggregates
cytotoxicity (Figure 1).
Cellular expression of PrP artificial mutants
Figure 1.BMC, a small molecule with PDI-like activity, abrogates CtmPrP cytotoxicity.
77
Physical Chemistry
To unveil the basis of PrP amyloid
polymorphism and its relation to
self-propagation
To generalize amiloidogenesis to
other pathogens following oral
route exposition
The structure and sequence of PrP β2-α2
loop dictates its conversion propensity and
interspecies prion transmission. Using rHaPrP
(23-231) with NN (wt, rigid loop), SN (Molike flexible loop) and NT (elk-like hyper rigid
loop) in 170 y 174 sequence positions we have
characterized the α-fold stability, fibril formation
and the amyloid state. The obtained results
support the hypothesis that the β2-α2 regulatory
elements function through the amyloid state
(Figure 2).
By virtue of the large environmental changes
taking place during food digestion we have
addressed the role of amyloid formation on
the allergenic activity of type-I food allergens.
Using as model Gad m1 (cod β-parvalbumin)
and a sequence analysis searching for adhesive
hexapeptides, a conformational characterization
under gastro-intestinal conditions and the
allergenicity evaluation we have found that IgEbinding activity is the amyloid assembly (Figure
3).
Figure 2. POM!-inmunoflurescence of amyloid fibrils formed by PrP NN, SN and NT chains.
Figure 3. the architecture of the IgE epitope on rGad m1 is its amyloid fibril.
78
Physical Chemistry
COMPETITIVE FUNDING
Ministerio de Ciencia e Innovación (MICINN)
TitleReference
M. Gasset
Role of methionine redox cycle on protein conformational diseases
BFU2009-07571
M. Gasset
PrPC processing as a risk factor for
Aβ-oligomer toxicity
FCIEN
M. Gasset
SDS-resistant aggregates
Raman Health
79
Physical Chemistry
Structural Bioinformatics Group
Pablo Chacón Montes (Assistant Professor) ReID ORCID SCOPUS
José Ramón López Blanco SCOPUS
Doctoral students
Erney Ramírez
80
Physical Chemistry
Summary
The Structural Bioinformatics Group (http://
chaconlab.org) is focused on developing
innovative techniques for the modeling, analysis
and simulation of molecular structures in
close contact with experimental labs. We are
particularly interested in large macromolecules
of dynamic composition and conformation whose
actions and interactions are essential for cellular
function. To better understand such systems,
we work on new bioinformatics tools for bridging
the resolution gap between atomic structures
with low to medium resolution experimental
data from different biophysical techniques (e.g.
X-ray crystallography, Electron microscopy,
SAXS, etc). Our research lines include efforts
to deal with the analysis and prediction of
molecular flexibility. We actively work to
effectively address the study and simulation
of the dynamics of large biomolecular systems
with Normal-Mode Analysis (NMA), geometric
algebra and other multiscale approximations.
We also expand our interest to understand
and forecast protein-protein and protein-ligand
molecular interactions. Our group employs and
develops computer-based methodologies (e.g.
virtual screening) to aid the rational design of
new compounds. The developed methodologies
are available via software distributions and web
servers.
Strategic Aims
• Bridging the resolution gap with hybrid methods. We develop new hybrid methods for
combining multiresolution structural information in collaboration with several experimental
labs.
• Multiscale dynamics of macromolecular biomachines. We address the study and simulation of
the dynamics of large biomolecular systems with NMA and other multiscale approximations.
• Atomistic molecular simulations. Our group employs MD simulation methods to examine a
variety of biological phenomena including protein interactions and macromolecular flexibility.
• Protein modeling. We develop tools for modeling protein structures and their interactions.
This includes novel methods for protein-protein docking and loop modeling problems.
• Exploring new strategies for structure-based rational design. Our group employs and develops
computer-based methodologies for drug discovery.
81
Physical Chemistry
Results
Hybrid methods
Advances in modern biology and medicine
depend on the understanding of the actions
and
interactions
of
large
biomolecular
complexes. The structural characterization of
such macromolecules can be only tackled with
coordinated application of complementary
biophysical
approaches.
Computational
hybrid methods bridge the gap between such
experimental techniques (Lopez-Blanco et al.
2015). Fitting is the standard way of interpreting
the
information
contained
in
electronmicroscopy (EM) maps of macromolecular
structures by means of the available atomic
structural components. This is a complicated
jigsaw puzzle in which the low-resolution 3D
EM density map of a macromolecule complex
acts as a fuzzy frame to guide the assemblage
of interlocking atomic-resolution pieces. When
complete, this puzzle allows to characterize at
near-atomic-detail different functional states of
the macromolecules in solution, and hence to
a better understanding of the inner workings
of the central actors in the principal cellular
processes. We develop several approaches to
try to solve this puzzle. For example, we recent
developed IMODFIT (Lopez-Blanco et al. 2013)
a flexible fitting tool based on NMA in internal
coordinates (see Figure 1). This and another
hybrid tools developed by us permitted the
characterization of intricate helix bundle that
dictates the assembly of the 26S proteasome lid
(Estrin et al. 2013).
Figure 1. Flexible fitting of the experimental map of thermosome. The initial pose was
obtained by rigid body fitting between the initial open atomic structure (cyan, PDB 1A6D)
and the corresponding closed experimental EM map (transparent surface, EMDB 1396) using
ADP_EM (). The final flexible fitted model based in a new approach using NMA in internal
coordinates is represented with a yellow ribbon.
82
Physical Chemistry
Multiscale simulations
Structural flexibility of biomolecules is closely
coupled to function, as evidenced by many
conformational changes observed on key cellular
process. Following the basic principle if you
know how it moves, you can infer how it works;
the knowledge of structural flexibility offers a
straight-line connection between structure and
function. Thus, inferring the intrinsic molecular
flexibility from a single conformation could offer
a direct link to understand likely large scale
rearrangements. We are addressing this problem
by simulation of the dynamics of biomolecular
systems with Normal-Mode Analysis (NMA)
(Lopez-Blanco et al. 2014a), geometric algebra
and other multiscale approximations. For
example, iMOD is a versatile toolkit to perform
NMA in internal coordinates (torsional space) on
both protein and nucleic acid atomic structures
(Lopez-Blanco et al. 2011). Our server, iMODS
(http://imods.chaconlab.org) facilitates the
exploration of such collective motions in
internal coordinates. Moreover, we developed
computational tools to extent NMA towards very
large systems (see Figure 2 and Lopez-Blanco
et al. 2013b).
Figure 2. Illustrative actin filament bending motions calculated using, IMOD, our NMA in
internal coordinates approach. The first three bending modes computed from the straight
experimental structure are shown.
83
Physical Chemistry
Protein modeling
We develop tools for modeling protein structures
and their interactions. Predict how two (or
more) proteins can interact from its individual
unbound components can reveal new insights in
the basic principles of molecular recognition and
hence in the key process on cellular functioning.
Moreover, the better understanding of proteinprotein interactions can be useful for structurebased drug design and other applications. Our
research interests include the development of
tools to address this otherwise high demanding
computational problem. Our first approximation,
FRODOCK, is focused on an initial stage
exhaustive docking (Garzón et al. 2007, see
also http://frodock.chaconlab.org). This stage
generates many potential predictions which will
be then assessed in a second refinement stage
or scoring step that we are currently developing.
We are also exploring new interacting potentials
(Krüge et al. 2013) as well as developing new
algorithms for protein-ligand docking using
GPUs (García et al. 2014).
We have validated the use of geometric algebra
(GA) in modeling macromolecular flexibility. We
have created a complete GA framework based
in a backward recursive approximation using
spinors (Chys & Chacon 2012) for efficient
chain manipulation. We are working now in
the effective incorporation of such GA tools in
our multiscale simulation approaches. We also
explored inverse kinematics problems, such as
local deformation and loop closure using GA
principles. Random Coordinate Descent (RCD)
is a versatile loop closure tool to generate
efficiently loop ensembles. The algorithm solves
loop closure by optimizing randomly selected
bonds and updating loop conformations by
spinor-matrices (see Figure 3, Chys & Chacon
2013 and check http://rcd.chaconlab.org ).
Figure 3. RCD loop closure solution of the protein test loop 1i0h.pdb (8-peptide, 145–152)
with (red) and without (green) geometric filters. The inclusion of grid filters improves the
sampling towards more feasible and clash-free solutions.
84
Physical Chemistry
Structure-based drug discovery and
design
Structure-based drug design and protein ligand
docking are effective and low cost strategies
for drug discovery. Our group employs and
develops computer-based methodologies to
aid the structure rational design of new active
compounds. As developers, we are particular
interested in virtual screening (VS) in where the
most interesting and promising ligand molecules
are computationally selected from very large
libraries of compounds. Our research lines include
the development of fast VS approximations on
GPUs. As users, we are actively collaborating in
multidisciplinary drug discovery projects using
the state of the art bioinformatics tools. We
already have an ongoing successful collaboration
in the rational drug design of the antibiotic
target FtsZ (Schaffner-Barbero et al. 2012). In
this context, we already identify new hits that
we are currently optimizing (Artola et al. 2015,
Ruiz-Avila 2013).
Atomistic molecular simulations
Our group employs MD simulation methods
to examine a variety of biological phenomena
including protein interactions and macromolecular
flexibility. Very recently, we report a state of
the art study of the FtsZ filament dynamics
interpreted in the context of the assembly cycle
of this essential cell division protein (Aportela et
al. 2014). In contrast with all previous studies
based on the inactive (not functional) closedcleft FtsZ conformation studies, our large scale
simulations studies disclose different filament
curvatures supported by nucleotide-regulated
interfacial dynamics. Moreover, we have
monitored, for the first time, the relaxation
from the active polymer conformation to the
inactive conformation of FtsZ monomers by
closing the cleft between the C-terminal domain
and helix H7. In agreement with experimental
data, these groundbreaking results unravel
the natural mechanism of the FtsZ assembly
switch. Integrating this assembly switch and
the nucleotide-dependent interfacial filament
stability, our work offers a detailed molecular
interpretation of the assembly-disassembly FtsZ
cycle and its inhibition. Recently an in-house
collaboration, we also helped to interpret the
selective recognition of microbial polysaccharides
by macrophage receptor SIGN-R1 (Silva-Martín
et al. 2014) using MD techniques.
Figure 4. Molecular model of compound 28 recognition by the FtsZ nucleotide binding site.
85
Physical Chemistry
Publications
Ramírez-Aportela E., López-Blanco J.R., Andreu
J.M., and Chacón P. (2014). Understanding
Nucleotide-Regulated FtsZ Filament Dynamics
and the Monomer Assembly Switch with LargeScale Atomistic Simulations. Biophys. J. 107,
2164–2176.
Silva-Martín N., Bartual S.G., RamírezAportela E., Chacón P., Park C.G., and Hermoso
J.A. (2014). Structural Basis for Selective
Recognition of Endogenous and Microbial
Polysaccharides by Macrophage Receptor
SIGN-R1. Structure 22, 1595–1606.
López-Blanco J.R., Miyashita O., Tama F. and
Chacón P. (2014a) Normal mode analysis in
structural biology (version 2.0). In: eLS. John
Wiley and Sons, Ltd: Chichester.
López-Blanco J.R., Aliaga J., Quintana-Ortí
E. and Chacón P. (2014b) iMODS: Internal
Coordinates Normal Mode Analysis Server.
Nucleic Acids Res. 42, W271-276
Krüger D.M., Garzón J.I., P. Chacon and H.
Gohlke (2014) DrugScorePPI KnowledgeBased Potentials Used as Scoring and
Objective Function in Protein-Protein Docking.
Plos One, 9(2):e89466
López-Blanco J.R. and Chacón P. (2013).
iMODFIT: efficient and robust flexible fitting
based on vibrational analysis in internal
coordinates. J. Struct. Biol. 184, 261–270
Ruiz-Avila L., Huecas S., Artola M., Vergoñós A.,
Ramírez-Aportela E., Cercenado E., Barasoain
I., Vazquez-Villa H., Martin-Fontecha M.,
Chacon P., Lopez-Rodriguez M.L. and Andreu
JM (2013). Synthetic inhibitors of bacterial cell
division targeting the GTP binding site of FtsZ.
ACS Chem. Biol. 8, 2072-2083
Estrin E., J.R. López-Blanco, P. Chacón, A.
Martin. (2013). Formation of an intricate
helical bundle dictates the assembly of the 26S
proteasome lid. Structure, 21, 1624–1635
López-Blanco J.R., R. Reyes, J.I. Aliaga, R.M
Badia, P. Chacón, E.S. Quintana-Ortí (2013)
Exploring Large Macromolecular Functional
Motions on Clusters of Multicore Processors. J.
Comp. 246, 275–288.
Chys P. and P. Chacón (2013). Random
coordinate descent with spinor-matrices and
geometric filters for efficient loop closure. J.
Chem. Theory Comput. 9, 1821–1829
86
Physical Chemistry
COMPETITIVE FUNDING
TitleReference
P. Chacón
Enhancing Macromolecular Sampling for Integrative Structural biology
BFU2013-44306P
Comunidad de Madrid
TitleReference
M. L. Rodríguez
Discover and Validation of therapeutic targets: development of the MHIT Platform.
CM S2010/BMD-2353
87
Physical Chemistry
Fluorescence and Molecular Biophysics Group
Mª Pilar Lillo Villalobos (Assistant Professor) ReID ORCID SCOPUS
A. Ulises Acuña Férnandez (Professor Ad honorem)
Doctoral students
Sebastian Raja (until 08/10/2013)
Technical Staff
Carolina García Rodríguez (TSE) ReID ORCID SCOPUS
88
Physical Chemistry
Summary
The overall objective of the Group is to understand
how biological systems work under physiological
conditions. With this aim we develop and
implement both theoretical and experimental
methods based on ps-resolved fluorescence
spectroscopy and two-photon laser excitation
microscopy, to provide the required temporal
(ps-s) and spatial (subµm- nm) resolution.
The
applications
include
biomolecular
conformational dynamics, organization and
interactions of multiprotein complexes, and lipid
microdomains distribution, in vitro, in living
cells, and tissues.
Strategic Aims
• Mechanism of action of bioactive compounds: Quantitative characterization of drug-target
interactions in the cell membrane and inside the cell.
• Detection, identification, localization and quantification of in vivo cell markers.
• Detection of lipid micro-domains in model membrane systems and living cells, induced by
bioactive compounds.
• 3-D organization, conformational dynamics and stoichiometry of multicomponent complexes.
• Spectroscopic characterization of fluorescent materials for biotechnological applications.
• Fundamental Photophysics. Design, synthesis, characterization and applications of emitting
molecular probes and fluorescent drugs.
89
Physical Chemistry
Results
Identification of antitumour drug
targets at the plasma membrane
and inside the cell. PharmaMar R & D
Contract
Characterization of Aplidin® interactions
in living cells.
Using fluorescence lifetime imaging (FLIM)
and phasor analysis (FLIM-phasor), we have
found three important molecular species in the
mechanism of action of the antitumor compound
Aplidin®, which are located in the plasma
membrane (species A), in the inner leaf and/
or very close to the plasma membrane regions
(species B), and in the cytoplasm (species C) of
sensitive (HeLa wt) and resistant (HeLa AplR)
cells treated with the fluorescent analogue of
Aplidin®, Apl-dmac (Figure 1).
We have detected complexes Apl-dmac/
eEF1A1-EGFP and Apl-dmac/ eEF1A2-EGFP in
the plasma membrane and inside the cell, using
fluorescence lifetime imaging, Förster resonance
energy transfer methods (FLIM-FRET), HeLa wt
and HeLa AplR cells expressing the elongation
factor labeled with the fluorescent protein eEGFP
(eEF1A1-EGFP or eEF1A2-EGFP). The location
and distribution of these complexes follow the
same pattern as species B and C.
We have detected Apl-dmac/eEF1A-EGFP
complexes in the plasma membrane, and close
to the inner leaf of the plasma membrane at
short times of interaction. At longer times
these complexes are distributed all over the
cytoplasm,
accumulating
in
well-defined
regions. These results support the importance
of the elongation factor as a relevant target in
the action mechanism of Aplidin®.
Figura 1. Identification of different molecular species of Aplidin® interacting with living
cells, using the FLIM-phasor approach. At short times, species A (Orange) is located in the
plasma membrane. Green, Light Blue and Dark Blue represent species C, indicating increasing
concentrations with time. λexc=750 nm (82MHz); λem=520/35 nm; T=37ºC.
90
Physical Chemistry
3D organization, dynamics and
stoichiometries
in
homoand
hetero-associations. Collaboration Dr.
A.Felipe (Univ. Barcelona)
Kv1.3 is a tetrameric protein which forms a
membrane channel leading K+ ions through
the cell membrane, in response to changes in
the membrane voltage. It has recently been
proposed that Kv1.3 interacts with the regulatory
protein KCNE4 with unknown stoichiometry.
We have studied the homo-association of
Kv1.3 and its interaction with the regulatory
protein KCNE4 using homo- FRET/ fluorescence
anisotropy images, FRET and FLIM-FRET,
combined with FLIM-phasor analysis in HEK293
living cells, expressing the fluorescent proteins
EGFP, mApple and mCherry tagged to Kv1.3 and
KCNE4.
Figure 2 shows FLIM and fluorescence anisotropy
images of a representative HEK293 cell and
a membrane region detail. An increase in the
fluorescence anisotropy is observed when the
cell is expressing a mixture of Kv1.3-EGFP and
unlabeled Kv1.3, due to a decrease in homoFRET because of the presence of unlabeled
Kv1.3 in the Kv1.3 tetramers.
Using the [Kv1.3-EGFP]4 complex as homo-FRET
and hetero-FRET controls, we have characterized
the organization and stoichiometry of [Kv1.3][KCNE4] complexes in the cell membrane.
Figure 2. Fluorescence lifetime (<t>; FLIM) and fluorescence anisotropy (r) images of a
representative HEK293 cell, expressing Kv1.3-EGFP or a mixture of Kv1.3-EGFP and Kv1.3.
λexc=850 nm (82MHz); λem=520/35 nm; T=37ºC.
91
Physical Chemistry
Detection of micro-domains and
dynamic organization of lipids in
the plasma membrane
The presence of ordered and disordered lipid
micro-domains in the plasma membrane of
HeLa cells was quantified using fluorescence
anisotropy images and lipophilic fluorescent
probes. The method used is based on the effects
of changes in the composition/lipid organization
on the rotational mobility of the fluorescent
probes inserted in the cell membranes. These
studies are complemented by generalized
polarization images (GP) of fluorescent probes as
Laurdan with photophysical properties sensitive
to the order and membrane fluidity.
Figure 3 shows how the average lipid order of
the plasma membrane decreases with time, in a
membrane detail of a HeLa cell treated with an
antitumor compound.
Figure 3. Plasma membrane detail of a representative HeLa cell, treated with an antitumor
compound, and labeled with the fluorescent probe TMA-DPH. Time variation of the lipid order
(0-1 min-max scale). λexc=750 nm (82MHz); λem=483/32 nm; T=37ºC.
92
Physical Chemistry
Fundamental photophysics
The first quantum model of the Triplet-Triplet,
diffusion-controlled energy transfer process,
in liquid solution, was completed in this period
(Zapata et al. 2014, J. Chem. Phys.), in
collaboration with Drs. O. Castaño, J.M. Frutos
and coworkers, from the Dept. of Physical
Chemistry of Alcalá University. Since the
reaction coordinate was defined as a function of
the energy and conformation of the intervening
electronic excited-states, it is now possible to
predict the transfer efficiency of this process
from spectroscopic information of the exchange
partners.
In collaboration with the same group, we carried
out a detailed ab initio computational study of
energies and conformation of singlet and triplet
states of fluorescent compounds, synthesized in
our laboratories, which present a binary effect
(0-1) on the fluorescence emission as a function
of pH (Acuña et al. 2013, Phys.Chem.Chem.
Phys.). Vertical excitation energies, computed
by TD-DFT using the HSE06 functional and
6-311++G(d,p) basis set, and solvent effects,
simulated with PCM approach, provided a
robust model of the mechanism underlying this
surprising quenching effect.
Finally, we collaborated with members of the
IUPAC Photochemistry Group to produce a
document (Ameloot et al. 2013, Pure Appl.
Chem.) recommending practices and reference
materials to improve the accuracy of stationary
and time-dependent fluorescence anisotropy
measurements in solution.
Design, synthesis, characterization
and
applications
of
emitting
molecular probes and fluorescent
drugs
In this period novel fluorogenic reactions were
discovered and optimized, directed to the
fluorescent labelling of important neurochemicals
as dopamine and DOPA. As a side-result of
this investigation, similar fluorogenic labelling
reactions were found applicable to antioxidants
as hydroxytirosol and salvianic acid, which give
rise to 100% fluorescent products.
In addition, we completed the study of
key biophysical properties in a membrane
environment of several fluorescent lipid
drugs
(alkyl-phosphocholines
and
lysophosphatidylcholines)
synthesized
in
our
laboratories. These compounds were also
applied in this period to the search of therapeutic
targets of the parent drug, to understand the
antitumor or antiparasite activity mechanism at
a molecular level.
93
Physical Chemistry
Publications
Martínez-Tong, D.E., Soccio, M., Sanz,
A., García, C., Ezquerra, T.A., Nogales,
A. (2013) Chain arrangement and glass
transition temperature variations in polymer
nanoparticles
under
3D-confinement.
Macromolecules 46, 4698-4705.
Acuña, A.U., Álvarez-Pérez, M., Liras, M.,
Coto P.B., Amat-Guerri, F. (2013). Synthesis
and photophysics of novel biocompatible
fluorescent oxocines and azocines in aqueous
solution. Phys. Chem. Chem. Phys. 15,
16704-16712.
Castro, B.M., Fedorov, A., Hornillos, V.,
Delgado, J., Acuña, A.U., Mollinedo, F., Prieto.
M. (2013). Edelfosine and miltefosine effects
on lipid raft properties: Membrane biophysics
in cell death by anti-tumor lipids. J. Phys.
Chem. B 117, 7929-7940.
Cuesta-Marbán, A., Botet, J., Czyz, O.,
Cacharro, L. M., Gajate, C., Bitew, T., Hornillos,
V., Delgado, J., Zhang, H., de la Iglesia-Vicente,
J., Amat-Guerri, F., Acuña, A.U. McMaster,
C.R., Revuelta, J.L., Zaremberg, V., Mollinedo,
F.
(2013). Drug uptake, lipid rafts and
vesicle trafficking modulate resistance to an
anticancer lysophosphatidylcholine analogue
in yeast. J. Biol. Chem. 288, 8405-8418.
Ameloot, M., vande Ven, M., Acuña A.U.,
Valeur, B. (2013). Fluorescence anisotropy
measurements: methods and reference
materials. Pure Appl. Chem. 85, 589-608.
Acuña, A.U., Santiuste, J.M. (2013). M. J.
Molera: cinética, fotoquímica y cromatografía
en la España de 1940-1980. An. Quim. 109,
31-33.
Martínez-Tong, D.E., Cui, J., Soccio, M., García,
C., Ezquerra, T.A., Nogales, A. (2014) Does
the glass transition of polymers change upon
3D-confinement? Macromol. Chem. Phys.
215, 1620-1624.
Zapata, F., Maruzzi, M., Castaño, O., Acuña,
A.U., Frutos, L.M. (2014).
Definition and
quantification of the Triplet-Triplet energy
transfer reaction coordinate. J. Chem. Phys.
140, 34102-3411.
de la Torre, B.G. , Hornillos, V., Luque-Ortega,
J.R. , Abengózar, M., Amat-Guerri, F., Acuña,
A.U., Rivas , L., Andreu, D. (2014) A BODIPYembedding miltefosine analogue linked to
cell-penetrating Tat(48-60) peptide favors
intracellular delivery and visualization of the
antiparasitic drug. Amino Acids 46, 10471058.
94
Physical Chemistry
COMPETITIVE FUNDING
TitleReference
M.P. Lillo
Dinámica e Interacciones de Biomoléculas mediante Espectroscopía de Fluorescencia
Polarizada con resolución espacial
CTQ-2010-16457
TitleReference
A.U. Acuña, (S. Marcos, I.P.)
Implante de lentes intraoculares mediante técnicas de “photobonding”
FIS2013-49544EXPLORA
Contracts and Agreements with Companies
R&D Contract CSIC-PharmaMar S.A.
TitleReference
M. P. Lillo
Estudio de las interacciones de Aplidina e Irvalec020101130001
con la membrana celularMTA: OTT20100279
95
Physical Chemistry
Protein Structure and Thermodynamic Group
Doctoral students
Margarita Menéndez Fernández
Radoslaw Borowski (from 1/09/2013)
Mª Dolores Solís Sánchez
Cristina Gallego Páramo
Lara López Merino (until 31/10/2013)
Ioanna Kalograiaki
Palma Rico Lastres
Mónica Álvarez Pérez ReID ORCID SCOPUS
Noemí Bustamante Spuch
Guadalupe García Medina
(until 30/06/2014)
Mª Asunción Campanero Rhodes
(until 5/01/2014) ReID ORCID SCOPUS
Technical Staff
Manuel Alberto Iglesias Bexiga
Mª Victoria López Moyano
Begoña Morales Juanós (from 11/02/2013)
96
Physical Chemistry
Summary
Knowledge of the structure and energetics of
proteins in solution provides information on the
nature of forces governing structural stability or
ligand recognition, among other properties. This
information is particularly relevant for proteins
of biomedical or technological interest, since it
facilitates a rational design of ligands (drugs,
vaccines, etc.), or the stabilization of proteins
themselves. In our group we have recently
studied, among other systems, different lectins,
pneumococcal cell wall hydrolases and other
proteins of biomedical interest. In addition, we
investigate the recognition of carbohydrates and
other compounds by these and other proteins,
with the final aim of elucidating their role in
numerous processes of biomedical relevance and
developing new diagnostic and/or therapeutic
strategies.
Strategic Aims
• Systematic characterization of the structural organization, stability and specificity in ligand
recognition of galectins and other human lectins.
• Unravelling of the structural and energetic basis for substrate recognition of pneumococcal cell
wall hydrolases. Search of inhibitors and design of new optimized enzymes with antimicrobial
activity.
• Development of novel designer microarrays.
97
Physical Chemistry
Results
Study
of
structure-function
relationships in galectins
Galectins are a family of endogenous lectins
that recognize b-galactosides in cellular
glycoconjugates and translate glycan signals into
cellular responses. They play important roles in
immune and inflammatory responses, cancer
and other biomedically relevant processes.
Characterization of the structure/function
relationships of galectins is a fundamental step
for a rational design of new diagnostic and
therapeutic strategies.
Galectins are divided into three structural
subgroups. Proto-type galectins contain one
or two (homodimeric) identical carbohydraterecognition domains (CRD). The chimera-type
galectin-3 consists in one CRD linked to a nonlectin N-terminal region composed of collagenlike repeats and an N-terminal peptide. Finally,
tandem-repeat-type galectins contain two
different CRDs covalently connected by a linker
peptide. In collaboration with Prof. H-J Gabius
(Ludwig-Maximilians-Universität),
we
have
studied the structural organization, stability and
binding properties of human galectins (hGal) of
the three subtypes.
Full-length hGal-3, eight trimmed variants
produced by removal of collagen-like repeats
(with/without the N-terminal stretch) and the
isolated CRD have been characterized to define
the structural and functional significance of the
N-terminal region. Their secondary and tertiary
structure has been investigated by circular
dichroism (CD), showing similar features for all
the variants and comparable lactose-induced
changes. However, a general tendency for an
increase in thermal stability with progressive
trimming has been observed. In addition,
dimerization is observed for some variants in
the absence of a ligand, whereas all the proteins
behave as monomers in the presence of lactose.
Precipitation studies with the glycoprotein
asialofetuin (ASF), a multivalent ligand for
galectins, have also revealed differences in the
crosslinking behaviour of the variants, in general
precipitation increasing with protein length,
evidencing that the presence of the N-terminal
region influences the ligand binding avidity of
the protein.
Similar studies have been carried out with the
tandem-repeat type hGal-4 and a variant with
shortened linker, hGal-4V. We have found that
hGal-4, but not hGal-4V, dimerize under nonreducing conditions. Analysis of the three
possible C/S hGal-4 mutants has demonstrated
linker-mediated dimerization via intermolecular
disulphide bridging, and precipitation assays
in the presence of ASF confirmed a significant
increase
in
crosslinking
activity
upon
dimerization.
Two different conformations have been detected
for homodimeric prototype hGal-7, due to a
trans/cis conformational switch of a proline
residue. Using size-exclusion chromatography,
CD-based assays and ITC, the impact of this
duality on protein features and ligand binding has
been examined. Of note, abrogation of trans/cis
isomerization by Pro to Leu mutation results in
a higher thermal stability of the protein. These
results open the discussion on the functional
relevance of hGal-7 conformational duality.
Studies on other galactose-specific
binding proteins
We have studied the structural organization
and stability of the human macrophage Galspecific lectin (hMGL), a type-II transmembrane
protein formed by a cytoplasmic domain, a
transmembrane region, and an extracellular
domain (ECD) consisting of a neck fragment
and a C-type (i.e. Ca+2-dependent) CRD specific
for Gal/GalNAc. HMGL is a key receptor for the
Tn carcinoma associated antigen. Clustering
of carbohydrate-binding sites in this and other
C-type receptors is crucial to increase binding
avidity and to ensure efficient recognition of
simple epitopes. We have found that the ECD of
the isoform 1 of hMGL exhibits an outstanding
oligomerization
capacity,
neck-mediated
disulphide-bridging playing a key role in the
formation of high-order multimers. CD studies
are consistent with a coiled coil structure for the
neck and reveal that the aromatic residues in
the vicinity of the high-affinity Ca+2-binding sites
within the CRD are unequivocal spectroscopic
markers of Ca+2 binding at these sites. In addition,
CD-based thermal denaturation experiments
have confirmed that both ECD and CRD exhibit
the same binding preferences, GalNAc inducing
the largest increase in stability. Altogether the
results indicate that the ECD is a well-structured
and functional sugar-binding protein that
forms high-order multimeric assemblies, with
important functional implications.
The non-human Gal-α-(1-3)-Gal disaccharide
epitope (or glycotope) is directly involved in the
hyperacute rejection (HAR) of porcine organ
xenografts. Although porcine organs could be
98
Physical Chemistry
suitable replacements for overcoming the critical
shortage of human organs, they express a high
proportion of the Gal-α-(1-3)-Gal epitope and
elicit a vigorous anti-Gal-α-(1-3)-Gal antibody
response. We have examined the recognition
of α-3-O-galactobiose by three different
scFv antibody fragments using CD. Similar
β-secondary structures and environment of
aromatic residues have been found for all scFvs,
but addition of Gal-α-(1-3)-Gal-β-1-OMe induces
scFv-specific changes in the CD spectra, their
intensity being directly related to the binding
affinity. Thermal denaturation experiments have
confirmed binding by the three scFvs, while
STD-NMR analysis carried out in parallel by Prof.
F.J. Cañada (CIB-CSIC) have served to identify
the recognized sugar epitopes.
Development
microarrays
of
new
designer’s
We have developed new designer’s microarrays
for the study of probe features and recognition
by different receptors. Using this technology,
we
can
incorporate,
and
subsequently
evaluate, different samples in a single chip,
from glycoproteins, glycolipids, or bacterial
lipopolysaccharides, up to intact bacteria
and cells. A protocol for the preparation and
validation of bacteria microarrays has been
established using Klebsiella pneumoniae as
model human pathogen, in collaboration with Dr.
J.A. Bengoechea (Fundación Caubet-Cimera).
The recognition of a set of defined mutants by
anti-Klebsiella antibodies and by the complement
subcomponent C1q, which binds K. pneumoniae
in an antibody independent manner, has been
demonstrated. Furthermore, the potential of
the bacteria microarray for investigating specific
features, e.g. glycosylation patterns, of the cell
surface has been confirmed by examining the
binding behavior of a panel of plant lectins with
diverse carbohydrate binding specificities.
This approach has also been used for exploring
the glycosylation profiles of wild-type and mutant
strains of non typable-Haemophilus influenzae
(NT-Hi), in collaboration with Dr. Junkal
Garmendia (Institute of Agrobiotechnology,
CSIC), of potential relevance to infectivity and
pathogenicity. The results evidence the presence
of β-galactosides on the bacterial surface and
provide a rationale for carbohydrate-mediated
recognition of NT-Hi by galectins.
Previous findings on the galectin- and straintype dependent selectivity towards NT-Hi have
prompted the study of galectin binding to newly
designed mutants bearing lipooligosaccharide
(LOS) trimming at selected positions. Wild
type and mutant LOS have been isolated and
quantitated using optimized electrophoretic
and colorimetric protocols. The entire bacteria
and purified LOSs have been printed in the
microarrays and the binding has been examined
in the absence and presence of potential
inhibitors. Remarkably, the results reveal
that hGal-4 and hGal-8 recognize different
LOS epitopes, an observation that could likely
account for the differential recognition of other
bacteria by these two galectins.
In addition, we have investigated the recognition
of Streptococcus pneumoniae (with and without
capsule) and other pathogens (S. mitis, S.
pyogenes and Staphylococcus aureus) as well as
different types of the cell walls (S. pneumoniae,
E. coli and Micrococcus spp.), all of them
incorporated in designer’ microarrays, by Cpl7,
its cell wall binding domain C-Cpl7, the mutant
R19A of C-Cpl7, and the protein variants without
one (Cpl7Δ1) or two (Cpl7Δ2) repetitions of the
cell wall binding domain. Among other results, it
is noteworthy the strong decrease in the affinity
of the R10A mutant of C-Cpl-7 for the bacteria
and the isolated cell wall. These microarrays
have been used also to investigate a possible
recognition of these bacteria by different
galectins, checking their binding specificity by
inhibition assays with asialofetuin/lactose.
Finally, we have also adapted the microarray
set-up for exploring the glycosylation patterns
of microvesicles and exosomes present in
circulating blood as well as those derived from
THP-1 neutrophils, in collaboration with Prof.
Edit Buzás (Semmelweis University). Specific
markers for each vesicle type have been used
for controlling immobilization and retention,
and array quality and integrity of the printed
vesicles has been assessed using an antiGAPDH antibody. Binding assays using the
panel of plant lectins have revealed different
glycosylation motifs among vesicle types, what
could be exploited for vesicle fractionation.
Study
of
structure-function
relationships
in
pneumococcal
murolytic enzymes. Development of
new antimicrobials
Streptococcus pneumoniae, the pneumococcus,
is the causative agent of opportunistic
infections and severe invasive diseases that
remain potentially life-threatening (mortality
rates surpass those of any other human
pathogen). The murein hydrolases encoded by
the pneumococcus and its bacteriophages are
potential targets for developing new therapeutic
strategies because of their capacity to modify
99
Physical Chemistry
Figure 1. Binding of biotinylated plant lectins to different vesicle populations. Serial
dilutions of pellet and supernatant (SN) of blood (1,3) and THP-1-derived (2,4) exosomes (1,2)
and microvesicles (3,4) were printed as triplicates onto nitrocellulose-coated glass slides and
incubated with biotinylated plant lectins at the indicated concentrations. The extent of lectin
binding was determined using streptavidin-AlexaFluor647®.
and disrupt the peptidoglycan network forming
the bacterial cell wall, un structure essential for
bacterial survival not shared by eukaryotic cells.
In-depth knowledge of pneumococcal murein
hydrolases can provide a rational to develop novel
therapeutic approaches aimed at i) interfering
the activity of the bacterial enzymes (involved
in fundamental processes for bacterial survival
and virulence) with specific inhibitors, and ii)
identifying or designing new murolytic enzymes
that, used in their purified form, can behave as
effective antimicrobials in the specific control
of pneumococcal infections. In collaboration
with the group of Bacterial Genetics at the
CIB (CSIC), our recent work on pneumococcal
murein hydrolases have focussed on functional
characterization of the glucosaminidase LytB,
the Cpl-7 endolysin, and four chimeric lysins
(Cpl-711, Cpl-771, Cpl-117 and Cpl177) built by
interchange of modules between Cpl-1 and Cpl7 endolysins.
In the search for determinants of substrate
specificity in pneumococcal murein hydrolases,
the catalytic residues of LytB, the minimal
hydrolysable substrate, and the nature of the
muropeptides hydrolyzed after treatment of cellwall isolates from different pneumococcal strains
with the enzyme have been characterized.
Among other results, a plausible model of a
tetrasaccharide-di-pentapeptide in complex with
the catalytic region (LytBCAT) has been generated
(Figure 2), and the hydrolysis mechanism,
compatible with the structural features and
substrate specificity, has been proposed. On the
other hand, the study of cell wall recognition by
the three fully conserved CW_7 motifs of C-Cpl-7,
carried out in parallel, has unveiled the key role
of the arginine residues located at position 19
of each motif on cell-wall binding. The analysis
was performed by NMR, in collaboration with Dr.
Marta Bruix from the Department of Biological
Physical-Chemistry, and using the microarray
technology (see above), while the crystal
structure of the triple R19A mutant of C-Cpl-7
was determined in collaboration with Dr. Juan
Hermoso from the Department of Structural
Biology.
In order to provide more effective and specific
antimicrobials against S. pneumoniae and other
pathogens, four functional chimeric lysozymes
with different substrate range were constructed
by swapping the structural domains of Cpl7 and Cpl-1 endolysins, in collaboration with
Dr. Pedro Garcia from the group of Bacterial
Genetics (CIB-CSIC). The chimeras Cpl-711
and Cpl-771 contained the catalytic domain and
the choline-binding domain of Cpl-7 and Cpl-1
endolysins, respectively, connected through the
linker peptides of Cpl-1 (Cpl-711) or Cpl-7 (Cpl771), whereas Cpl-117 and Cpl-177 comprised
the catalytic domain of Cpl-1 and the cell wall
binding domain of Cpl-7S (an improved variant
of the Cpl-7 endolysin) joined, again, by the
linker peptides of Cpl-1 or Cpl-7, respectively.
As expected, the activity of Cpl-711 and Cpl771 was choline dependent whereas Cpl-117
and Cpl-177 hydrolyzed the cell walls in a
choline-independent way, and their specific
activities on pneumococcal cell wall fragments
were similar. However, the chimera Cpl-711
substantially improved the killing activity of
the parental lysozymes against pneumococcal
100
Physical Chemistry
bacteria, including multiresistant strains, both
in vitro and in vivo. The protection provided by
a single intraperitoneal injection of Cpl-711 to
mice challenged with the pneumococcal D39
strain was 50% greater than with Cpl-1. This
makes of Cpl-711 the most powerful enzybiotic
against pneumococci so far described and
opens a promising therapeutic perspective for
the treatment of multiresistant pneumococcal
infections.
Finally, activity assays in the presence of
compounds identified as potential ligands of
the LytA autolysin in thermal-shift assays have
allowed the identification of an inhibitor whose
binding affinity and mechanism of action are
currently under investigation.
Other systems of interest
The group activities also included collaborations
with different research groups aimed to
the structural
and/orther
modynamic
characterization of biomolecules and their
complexes. Because of their biological or
biotechnological relevance we can point out
the studies performed on the CPEB protein and
its non-toxic, amyloid-like orthologue Orb2, in
collaboration with Dr. Mariano Carrión (Cajal
Institute, CSIC); the sugar recognition by the
carboxy-terminal head domain of the fiber from
different adenovirus, in collaboration with Dr.
van Raaij (CNB, CSIC); and the self-association
of the MgaSpn protein from Streptococcus
pneumonaie, involved in virulence, in cooperation
with Dr. Alicia Bravo (CIB, CSIC).
Figure 2. Model of the
complex formed by the
catalytic region of LytB
and the dipentapeptide
tetrasaccharide (NAGNAM-L-Ala-D-isoGln-L-LysD-Ala-D-Ala)2. The GH73
domain is represented in
red, SH3B in yellow and the
WW-type domain in Green.
The ligand (stick model) is
shown with the carbon atoms
coloured in green, oxygens in
red and nitrogens in blue. The
discontinuous lines indicate
possible hydrogen bonds.
101
Physical Chemistry
Publications
Carrero, P., Arda, A., Alvarez, M., Doyaguez,
E.G., Rivero-Buceta, E., Quesada, E., Prieto,
A., Solís, D., Camarasa, M.J., Pérez-Pérez, M.J.,
Jiménez-Barbero, J., San-Felix, A. (2013).
Differential recognition of mannose-based
polysaccharides by tripodal receptors based
on a triethylbenzene scaffold substituted with
trihydroxybenzoyl moieties. European J.
Org. Chem. 1, 65-76.
Garcia-Linares, S., Castrillo, I., Bruix, M.,
Menéndez M., Alegre-Cebollada, J., Martínezdel-Pozo, A., Gavilanes, J.G. (2013) Threedimensional structure of the actinoporin
sticholysin I. Influence of long-distance
effects on protein function. Arch. Biochem.
Biophys. 532, 39-45.
Ruiz, F.M., Fernández, I.S., López-Merino
L., Lagartera, L., Kaltner, H., Menéndez, M.,
André, S., Solís D., Gabius, H.-J., Romero,
A. (2013) Fine-tuning of prototype chicken
galectins: Structure of CG-2 and structureactivity correlations. Acta Cryst. D: Biol.
Cryst. 69, 1665-1676.
Diez-Martínez, R., De Paz, H., Bustamante,
N., García. E., Menéndez M., García P.
(2013) Improving the lethal effect of Cpl-7,
a pneumococcal phage lysozyme with broad
bactericidal activity, by inverting the net charge
of its cell wall-binding module. Antimicrob.
Agents. Chemother. 57, 5355-5365.
Ermakova, E., Miller, M.C., Nesmelova, I.V.,
López-Merino, L., Berbis, M.A., Nesmelov, Y.,
Tkachev, Y.V., Lagartera, L., Daragan, V.A.,
André, S., Cañada, F.J., Jiménez-Barbero, J.,
Solís, D., Gabius, H.-J., Mayo, K.H. (2013)
Lactose binding to human galectin-7 (p53induced gene 1) induces long-range effects
through the protein resulting in increased
dimer stability and evidence for positive
cooperativity. Glycobiology 23, 508–523.
Ruiz, F.M., Scholz, B.A., Buzamet, E., Kopitz,
J., André, S., Menéndez, M., Romero, A.,
Solís, D., Gabius, H-J. (2014) Natural single
amino acid polymorphism (F19Y) in human
galectin-8: Detection of structural alterations
and increased growth-regulatory activity on
tumor cells. FEBS J. 281, 1446-1464.
Moscoso, M., Esteban-Torres, M., Menéndez,
M., García, E. (2014) In vitro bactericidal
and bacteriolytic activity of ceragenin CSA13 against planktonic cultures and biofilms
of Streptococcus pneumoniae and other
pathogenic streptococci. PLos ONE 9,
e101037.
Solís, D., Bovin, N.V., Davis, A.P., JiménezBarbero, J., Romero, A., Roy, R., Smetana
Jr. K., Gabius H.-J. (2014) A guide into
glycosciences: How chemistry, biochemistry
and biology cooperate to crack the sugar code.
B.B.A (Epub 2014 Mar 28).
102
Physical Chemistry
COMPETITIVE FUNDING
MINECO
TitleReference
M. Menéndez
Structural variability and substrate fine specificity of two families of biomedical relevant proteins
BFU2009-10052
M. Menéndez
Exploring exogenous and endogenous factors as tools for the control of infectious and immune
processes
BFU2012-36825
CAM
TitleReference
F. Gago
Bioinformatics integrative platform for structure E-based drug discovery (BIPEDD2)
S2010/BMD-2457
UE
TitleReference
L. Joshi
Glycomics by High-throughput Integrated Technologies:
M. Barboiu
Dynamic interactive nanosystems (DYNANO)
FP7-ITN-GA:289003
D. Solís
The Sugar Code: from (bio)chemical concept to clinics (GLYCOPHARM)
FP7-ITN-GA:317297
(FP7-Health 2010-
260600)
Development and validation of complementary
and integrated technologies for glycomic analysis
of serum in cancer, glycobiomarker discovery,
diagnostics and glycotherapeutic monitoring
(GlicoHIT)
103
Physical Chemistry
Nmr Spectroscopy of Nucleic Acids Group
Carlos González Ibáñez (Professor) ReID ORCID
Douglas Vinson Laurents (Assistant Professor) ReID ORCID
Irene Gómez Pinto
Doctoral students
Miguel Garavís Cabello
Nerea Martín Pintado (hasta 13/06/2013)
Miguel Mompean García
Technical Staff
David Pantoja Uceda (TSE)
Miguel Angel Treviño Avellaneda (TSE) ReID ORCID SCOPUS
Diana Velázquez Carreras (JAE-TEC)
104
Physical Chemistry
Summary
The chief objective of our group is to contribute
to the understanding of molecular recognition
events involving nucleic acids. These events are
implicated in a myriad of processes of interest
for Biology, Nanoscience and Macromolecular
Chemistry.
Understanding these processes
has a direct impact on the development of new
drugs.
One
key
approach
to
comprehend
these
molecular recognition processes is to know the
3D structure of nucleic acids (DNA, RNA and
their derivatives) at the highest level of detail
possible. To this end, our group is dedicated to
the determination of oligonucleotide structures
either alone or in complex with proteins
and other ligands. We use a diverse set of
spectroscopic techniques, principally Nuclear
Magnetic Resonance (NMR) Spectroscopy.
Strategic Aims
• Structural studies of nucleic acid analogs and non-canonical structures important in Biology
and Nanoscience.
• Structural studies of nucleic acids implicated in human diseases and their complexes with
ligands.
• Contribute to the elucidation of hypothetical molecular recognition processes and co-evolution
between RNA and proteins during the Origin of Life.
• Study the formation and stability of the products of abnormal RNA translation, such as
amyloids.
105
Physical Chemistry
Results
Studies of nucleic acid - ligand
interactions
The research on RNA - ligand interactions over
these two years can be classified into two
groups. First, we have continued our studies
of the effects of aromatic ligands on the DNA
sequences that form quadruplexes and we have
made notable advances in the study of several
DNA-ligand conjugates. These conjugates are
diverse and range from DNA double helices to
quadruplexes. Second, we have undertaken the
identification of new ligands for human telomeric
RNA utilising innovative methods that we will
describe in the next section.
Figure: Close up view of the interaction between a carbohydrate and a guanine quadruplex.
106
Physical Chemistry
New Methods
From the technical perspective, we have
developed new protocols for the production
and purification of relatively long molecules of
RNA in quantities and purities sufficient for NMR
structural studies. Using these new methods, we
have produced telomeric RNAs (TERRAS) which
contain 100 nucleotides. Our collaboration with
the group of Alfredo Villasante (CBMSO-CSIC)
has been fundamental for this task. We have
characterised the TERRA RNAs using NMR,
CD, and optical tweezers in collaboration with
Ricardo Arias (IMDEA).
Working with Dr. Ramon Campos (CNIO), we have
implemented 19F NMR based methodologies to
detect weak interactions between large RNA
molecules and ligands labeled with fluorine.
This has permitted us to explore the affinity
of a library of compounds for human telomeric
RNA and to identify new ligands for RNA
quadruplexes. We have also collaborated with
Juan Luis Asensio (IQO-CSIC) to develop a new
strategy for identifying the ligands derived from
amino glycosides that bind the most effectively
to RNA.
Cartoon illustrating the structure of a segment of human telomeric RNA (TERRA) the effect that
its presence produces on the signal 19F NMR signal of fluorine labeled ligands.
107
Physical Chemistry
Studies of Chemically
Nucleic Acids
Modified
We have continued our studies of the effect
of fluorine at the 2’ position on the pentose
sugar ring. We have carried out the structural
determination of the self
complementary
chimeric duplexes 2F’-ANA/2F’-RANA in a
number of diverse sequences. These studies
aid our comprehension of the structural bases of
the stabilisation afforded by fluorine substituted
ribose (2’F -RANA) and arabinose (2’F -ANA)
sugars. Moreover, these results could be used to
obtain better compounds for antisense therapy
and RNA silencing.
Moreover, we have carried out structural studies
on guanine quadruplexes containing fluorine
labeled nucleotides. Our results with telomeric
sequences indicate that the presence of a single
fluorine labeled nucleotide is able to modify and
markedly stabilise the quadruplex structure.
Figure: Structure of an RNA duplex modified with 2’F-ANA and 2’F-RNA. Dotted lines indicate
the pattern of non conventional H-bonds in the sugar backbone provoked by the presence of
fluorine atoms.
108
Physical Chemistry
Amyloid beta sheets
We have aimed to characterize the first
steps in the formation of amyloids using
NMR. However, the low concentration of the
key intermediates and their rapid evolution
towards large aggregates makes it difficult to
characterise them by NMR spectroscopy. For
this reason, we have realised these studies
using computational methods. Specifically, we
have used long Molecular Dynamics simulations
(up to half a microsecond) to characterise the
smallest oligomers formed by the Sup35 amyloid
(sequence GNNQQNY), and QM/MM calculations
to quantify how much the intra-sheet H-bonds
strengthenes as the sheet grows. The experience
gained from studying this peptide has allowed us
to tackle the identification and characterisation
of the amyloid forming segment of TDP-43,
a 414 residue human protein implicated in
Amyotrophic Lateral Sclerosis.
In collaboration with Dr. M. Carrión-Vázquez
(Cajal Institute) we have studied the
conformational diversity present in proteins
and amyloidogenic peptides implicated in
diverse neurodegenerative diseases, such as
Alzheimer’s, Parkinson’s and Huntington´s.
Despite their different sequences, all these
proteins undergo a similar conformational
change in which random coils adopt structures
rich in beta sheet. These findings have lead us
to propose that conformational changes in the
monomer trigger the formation of amyloid. In
many cases, this crucial conformational change
can be blocked by the peptide inhibitor QBP1
(sequence: WKWWPGIF). As a first step towards
developing more effective inhibitors, we have
determined QBP1’s structure using NMR.
Cross-eyed stereo view of the preferred conformation of QBP1 (color code W, K, P, G, I, F)
109
Physical Chemistry
Putative prebiotic peptides
Over the last several years, we have studied
different peptides composed of the small subset of amino acids that could have formed on the
prebiotic Earth. Some of these peptides adopt
a well folded tetrameric structure composed of
four alpha helices. During 2013-2014, we set
out to determine if other simple peptides could
form beta hairpins, the fundamental building
blocks of β-sheets. The general sequence of
these peptides is HφIKIDGKφIKH, where φ
is H, F or W. We found that only the peptide
with 2 Trps could adopt a high population of
beta hairpin structure. Moreover, we found that
KIA²W and KIA²F (the variant with 2 Phe) bind
to ATP and with less affinity to GTP to form 1:1
complexes. The elucidation of the structure
of the KIA²W·ATP complex revealed that the
adenine base inserts between two Trp indole
rings, and that the phosphates of ATP and the
ammonium groups of the lysines associate
through favorable electrostatic interactions.
This structure is the first determination of an
ATP·²-hairpin complex.
Cross-eyed stereo view of the ATP(maroon )+ KIAβW (W, K, H, D, I) complex.
110
Physical Chemistry
Publications
Hervás, R, Fernández-Ramírez, M.C., Abelleira,
L.E., Laurents, D.V. and Carrión-Vázquez,
M. (2014). Chapter 6: Nanomechanics
of Neurotoxic Proteins: Insights at the
Start of the Neurodegeneration Cascade.
“Bio-nanoimaging: Protein Misfolding and
Aggregation”. Pages 57-68. ISBN: 978-0-12394431-3.
Benabou, S., Avino, A., Eritja, R., Gonzalez, C.
and Gargallo, R. (2014). Fundamental aspects
of the nucleic acid i-motif structures. RSC
Advances 4, 26956-26980.
Benabou, S., Ferreira, R., Avino, A., Gonzalez,
C., Lyonnais, S., Sola, M., Eritja, R., Jaumot,
J. and Gargallo, R. (2014). Solution equilibria
of cytosine- and guanine-rich sequences near
the promoter region of the n-myc gene that
contain stable hairpins within lateral loops.
Biochim Biophys Acta 1840, 41-52.
Doluca, O., Hale, T.K., Edwards, P.J.B.,
González, C. and Filichev, V.V. (2014).
Assembly-dependent fluorescence enhancing
nucleic
acids
(AFENA)
in
sequencespecific detection of double-stranded DNA.
ChemPlusChem 79, 58-66.
Garavis, M., Lopez-Mendez, B., Somoza,
A., Oyarzabal, J., Dalvit, C., Villasante, A.,
Campos-Olivas, R. and Gonzalez, C. (2014).
Discovery of selective ligands for telomeric RNA
G-quadruplexes (TERRA) through 19F-NMR
based fragment screening. ACS Chem Biol 9,
1559-1566.
Lucas, R., Penalver, P., Gomez-Pinto, I.,
Vengut-Climent, E., Mtashobya, L., Cousin, J.,
Maldonado, O.S., Perez, V., Reynes, V., Avino,
A., Eritja, R., Gonzalez, C., Linclau, B. and
Morales, J.C. (2014). Effects of sugar functional
groups, hydrophobicity, and fluorination on
carbohydrate-DNA stacking interactions in
water. J Org Chem 79, 2419-2429.
Martinez-Montero, S., Deleavey, G.F., Kulkarni,
A., Martin-Pintado, N., Lindovska, P., Thomson,
M., Gonzalez, C., Gotte, M. and Damha, M.J.
(2014). Rigid 2’,4’-difluororibonucleosides:
synthesis, conformational analysis, and
incorporation into nascent RNA by HCV
polymerase. J Org Chem 79, 5627-5635.
Mompean, M., Buratti, E., Guarnaccia,
C., Brito, R.M., Chakrabartty, A., Baralle,
F.E. and Laurents, D.V. (2014). Structural
characterization of the minimal segment of
TDP-43 competent for aggregation. Arch
Biochem Biophys 545, 53-62.
Mompean, M., Gonzalez, C., Lomba, E. and
Laurents, D.V. (2014). Combining Classical
MD and QM calculations to elucidate complex
system nucleation: a twisted, three-stranded,
parallel beta-sheet seeds amyloid fibril
conception. J Phys Chem B 118, 7312-7316.
Ramos-Martin, F., Hervas, R., CarrionVazquez, M. and Laurents, D.V. (2014). NMR
spectroscopy reveals a preferred conformation
with a defined hydrophobic cluster for
polyglutamine binding peptide 1. Arch
Biochem Biophys 558, 104-110.
Escaja, N., Gomez-Pinto, I., Viladoms, J.,
Pedroso, E. and Gonzalez, C. (2013). The
effect of loop residues in four-stranded dimeric
structures stabilized by minor groove tetrads.
Org Biomol Chem 11, 4804-4810.
Garavis, M., Bocanegra, R., Herrero-Galan,
E., Gonzalez, C., Villasante, A. and AriasGonzalez, J.R. (2013). Mechanical unfolding
of long human telomeric RNA (TERRA). Chem
Commun (Camb) 49, 6397-6399.
Garavis, M., Gonzalez, C. and Villasante,
A. (2013). On the origin of the eukaryotic
chromosome: the role of noncanonical DNA
structures in telomere evolution. Genome
Biol Evol 5, 1142-1150.
Gomez-Pinto, I., Vengut-Climent, E., Lucas, R.,
Avino, A., Eritja, R., Gonzalez, C. and Morales,
J.C. (2013). Carbohydrate-DNA interactions at
G-quadruplexes: folding and stability changes
by attaching sugars at the 5’-end. Chemistry
19, 1920-1927.
Hospital, A., Faustino, I., Collepardo-Guevara,
R., Gonzalez, C., Gelpi, J.L. and Orozco, M.
(2013). NAFlex: a web server for the study of
nucleic acid flexibility. Nucleic Acids Res 41,
W47-W55.
Jimenez-Moreno, E., Gomez-Pinto, I., Corzana,
F., Santana, A.G., Revuelta, J., Bastida, A.,
Jimenez-Barbero, J., Gonzalez, C. and Asensio,
J.L. (2013). Chemical interrogation of drug/
111
Physical Chemistry
RNA complexes: from chemical reactivity to
drug design. Angew Chem Int Ed Engl 52,
3148-3151.
(2013). (1)H, (13)C and (15)N resonance
assignments of the Onconase FL-G zymogen.
Biomol NMR Assign 7, 13-15.
Martin-Pintado, N., Deleavey, G.F., Portella, G.,
Campos-Olivas, R., Orozco, M., Damha, M.J.
and Gonzalez, C. (2013). Backbone FC-H...O
Hydrogen Bonds in 2’F-Substituted Nucleic
Acids. Angew Chem Int Ed Engl 52, 1206512068.
Amiri, R., Bordbar, A.K., Laurents, D.V. (2014)
Gemini surfactants affect the structure,
stability, and activity of ribonuclease Sa. J
Phys Chem B. 118, 10633-42.
Martin-Pintado, N., Yahyaee-Anzahaee, M.,
Deleavey, G.F., Portella, G., Orozco, M., Damha,
M.J. and Gonzalez, C. (2013). Dramatic effect
of furanose C2’ substitution on structure and
stability: directing the folding of the human
telomeric quadruplex with a single fluorine
atom. J Am Chem Soc 135, 5344-5347.
Santana, A.G., Jimenez-Moreno, E., Gomez,
A.M., Corzana, F., Gonzalez, C., Jimenez-Oses,
G., Jimenez-Barbero, J. and Asensio, J.L.
(2013). A Dynamic Combinatorial Approach for
the Analysis of Weak Carbohydrate/Aromatic
Complexes: Dissecting Facial Selectivity in
CH/pi Stacking Interactions. J Am Chem Soc
135, 3347-3350.
Serrano, S., Callis, M., Vilanova, M., Benito,
A., Laurents, D.V., Ribo, M. and Bruix, M.
Gotte, G., Laurents, D.V., Merlino, A., Picone,
D., Spadaccini, R. (2013) Structural and
functional relationships of natural and artificial
dimeric bovine ribonucleases: new scaffolds
for potential antitumor drugs. FEBS Lett.
587(22), 3601-8.
Diez-García, F., Pantoja-Uceda, D., Jiménez,
M.Á., Chakrabartty, A., Laurents, D.V. (2013).
Structure of a simplified β-hairpin and its ATP
complex. Arch Biochem Biophys. 537(1),
62-7.
Callís, M., Serrano, S., Benito, A., Laurents,
D.V., Vilanova, M., Bruix, M., Ribó, M. (2013).
Towards tricking a pathogen’s protease
into fighting infection: the 3D structure of a
stable circularly permuted onconase variant
cleavedby HIV-1 protease. PLoS One
8(1):e54568.
112
Physical Chemistry
COMPETITIVE FUNDING
TitleReference
Laurents, D.V.
Structure, Stability and Optimization of QBP1 + CPEB Prion Domain Complexes x
and in Memory Consolidation
SAF2013-49179-C2-2-R
Laurents, D.V.
Structure, solvation and ligand binding of RNAs and Proteins with Aberrant Conformations by NMR
CTQ2010-21567-C02-02
TitleReference
Carlos González Ibáñez
Estudios estructurales de oligonucleotidos modificados ricos en guaninas mediante RMN
PRI-AIBNZ-2011-0919
Acción integrada con
Nueva Zelanda
113
Physical Chemistry
Department of Low Dimensional
Systems, Surfaces and
Condensed Matter
Memoria 2013/2014 Department of Biological Physical
115
Chemistry
Introduction
The
Department
of
low-dimensional
systems, surfaces and condensed matter is
composed by various groups of the Institute
“Rocasolano” who share a common interest
in Materials Science. The Department has
well-defined lines of research devoted to the
synthesis, characterization and modeling
of materials with applications such as
optoelectronics,
photonics,
biomedicine,
magnetism, catalysis, electrocatalysis and
energy conversion and storage (to name a
few).
An important part of the investigation of
this Department is dedicated to the study
of laser-induced processes in molecules
and materials. The use of laser ablation
for the generation of nanostructures, the
implementation of new laser techniques for
processing and synthesizing materials or the
study of new organic dyes for laser emission
are just some of the many aspects developed
in the Department.
Another major part of the Department
activities comprises the theoretical and
experimental study of surfaces and thin
films, molecular aggregates and properties
of condensed matter, at the atomic and
molecular scales, with the ultimate aim
of understanding phenomena of surface
reactivity such as adsorption, corrosion or
electrocatalysis.
The
Department investigation
is not
constituted only by the individual addition
of the research of the different groups that
compose it. In the biennium to which this
report (2013-2014) is concerned, there
have been a significant number of intradepartmental collaborations that have been
reflected in a significant number of joint
scientific publications.
In the last two years the Department has
experienced a significant reduction in its
potential. To the retirements occurred in the
previous biennium (2011-2012) we have
to add the leave of Dr. Angel Cuesta to the
University of Aberdeen (UK) and that of the
group of Prof. García de Abajo to the ICFO in
Catalonia. In practice, this has meant, in the
first case, the complete dismantling of the
group of Electrochemistry and, in the second,
the disappearance of the Nanophotonics
group. The disappearance of the group of
Electrochemistry group results particularly
painful since it means the end of the dedication
to a discipline that has been fundamental for
decades in the work of “Rocasolano” Institute
and that has provided a very prestigious
reputation both at national and international
levels.
Scientific Report 2013/2014 Department of Low Dimensional Systems,
116
Surfaces and Condensed Matter
Group Structure
Lasers, Nanostructures and Materials Processing
118
Laser Materials and Laser-Materials Interaction
129
Statistical Mechanics and Condensed Matter
138
Surface Analysis and Mössbauer Spectroscopy
145
117
Lasers and Nanostructures and Materials
Processing Group
Doctoral students
Marta Castillejo Striano
Ignacio López Quintás
Margarita Martín Muñoz
(Associate Professor) ReID
Technical Staff
Rebeca de Nalda Mínguez
Antonio Benítez Cañete
(JAE-Tec. Until 16/10/2013)
Esther Rebollar González
(Ramón y Cajal) ReID ORCID SCOPUS
Mohamed Oujja Ayoubi
ReID ORCID SCOPUS
Mikel Sanz Monasterio (Until 21/02/2014)
118
Summary
The activity of the Group has focused on the
research on the physics and chemistry of
micro- and nanofabrication processes using
pulsed laser irradiation and ablation in the
nanosecond and femtosecond temporal domains
and wavelengths from UV to IR. We have
concentrated on the controlled generation of a
broad range of nanomaterials and nanostructures
with specific functionalities based on polymers,
semiconductors, oxides and polymer/inorganic
composites. Our work has unravelled basic
laser interaction mechanisms allowing us to
propose new experimental methods to control
the composition, morphology and structure of
the fabricated nanomaterials. We have also
directed our efforts towards the development
of new experimental methodologies to extract
physicochemical information about the different
types of nanostructures. Our results are of
interest for applications in biomedicine, sensing,
photovoltaics, photonics, electronics, magnetic
materials and cultural heritage.
Strategic Aims
We aim at achieving controlled fabrication of nanomaterials and nanostructures with specific
functionalities by laser irradiation through the fundamental understanding of the laser writing
and ablation of materials and the study of the properties of the ablation plasma. The specific
objectives are:
• To design and fabricate polymer nanostructures and polymer-based nanocomposites with
tailored properties by superficial laser writing.
• To obtain, by laser ablation and deposition, nanostructured deposits with magnetic ordering
based on iron oxides and to control the doping of II-VI semiconductors with transition metal
atoms.
• To develop novel methodologies for in situ determination of the growth and self-assembly
processes of the laser generated nanomaterials.
• To identify targets and ablation regimes yielding plasmas with high efficiency for harmonic
generation.
• The development and application of laser-based methodologies for the analysis and
conservation of substrates and objects of Cultural Heritage.
119
Results
Generation
of
superficial
nanostructures by laser irradiation
We have continued our studies on the generation
of superficial periodic nanostructures by laser
irradiation (laser induced periodic surface
structures, LIPSS). Together with substrates
constituted by films of synthetic polymers, we
have demonstrated LIPSS generation in different
materials such as biocompatible biopolymers
and semiconductors.
To develop new strategies for the control of the
morphology and superficial chemistry of the
generated nanostructures, we have undertaken
the generation of LIPSS with ultrashort laser
pulses in the femtosecond scale, and different
wavelengths from the UV to the IR. In this
case, we have determined the dependence
of the period with laser wavelength (Fig. 1).
Besides, with temporally shaped ultrashort laser
pulses we have demonstrated an active control
of the properties of the generated superficial
nanostructures generated on biopolymer films.
Within this topic it is worth pointing out the
application of the GISAXS (grazing incidence
small angle X ray scattering) technique to
monitor periodic structures in thin polymer
films generated by LIPSS approach and also
by NIL (nanoimprint lithography). We have
undertaken an investigation on the use of
polymer films endowed with LIPSS as substrates
for cell growth, successfully demonstrating the
adhesion and proliferation of mesenchymal
cells on polyethylene terephthalate (PET) based
substrates.
Part of the work here reported has taken place in
collaboration with the group of Prof. T. Ezquerra,
Instituto de Estructura de la Materia, CSIC.
Figure 1. AFM height images of films of polytrimethylene terephthalate (PTT) irradiated at
the given fluences, number of pulse and wavelengths. The height profile along a 5 µm line
perpendicular to the ripples is shown below every image (height scale: 250 nm). The double
arrow indicates the laser polarization direction. Adapted from Rebollar et al., 2013.
120
Laser ablation for the fabrication of
thin films and nanostructures
We have used laser transfer techniques, based
in the ablation of a solid target to fabricate
thin films and nanostructures with specific
functionalities. By pulsed laser deposition (PLD)
using a nanosecond IR laser (1064 nm) we
have determined the dependence with the type
of substrates of the morphology, structure and
magnetic properties of deposits grown from
hematite targets. While on silicon substrates
we have confirmed the growth of stoichiometric
magnetite, on SrTiO3:Nb substrates we observe
magnetite domains magnetized along the inplane <100> directions (Fig. 2). Magneto-optical
Kerr effect measurements show that the maxima
of the remanence and coercivity are also along
in-plane <100> film directions. This easy-axis
orientation differs from bulk magnetite and films
prepared by other techniques, establishing that
the magnetic anisotropy can be tuned by film
growth. These studies have been carried out
with the collaboration of Drs Juan de la Figuera
and J.F. Marco of IQFR.
By laser irradiation of ZnS/Co(2%) targets,
with nanosecond pulses of 1064 nm, we have
observed, for the first time reported in ablation
plasmas, the presence Co substituted (ZnS)
clusters. Analysis by EDS and cross-sectional
n
HRTEM of plasma species, deposited on a Si
substrate, allow the identification of crystalline
nanoparticles
with
average
composition
Zn0.96Co0.04S. These results open a possible
path of controlled synthesis, via PLD, based
on the hypothesis that selected compositions
of bimetallic clusters, ZnnComSk, are formed in
the plasma, and behave as building blocks and
self-assemble in nanostructures with magnetic
functionality, maintaining the semiconductor
transport properties.
In PLD, the structural and chemical characteristics
of deposits depend of the properties of the
ablation plume, composition and dynamics of
species, in route from the target to the substrate,
and to the nucleation processes on the substrate
itself. By optical emission spectroscopy, timeof-flight mass spectrometry and low-order
harmonic generation of a probe laser we have
undertaken the characterization of laser ablation
plasmas of targets constituted by SiO, ZnS-Co
and TiO2, where we have identified neutral and
ionized atomic species, clusters (as mentioned
in the paragraph above, or nanoparticles.
A second laser transfer technique, such as
pulsed laser ablation in liquid medium (PLAL),
has served us to obtain colloidal Pt nanoparticle
solutions which we have used to fabricate
photoactive substrates. We have demonstrated,
in collaboration with the group of Prof. Bruno
Martínez-Haya, of Universidad Pablo de Olavide,
Sevilla, a significant increase of sensitivity and
response in the detection of using the techniques
de nanoparticle-assisted laser desorption/
ionization (NALDI), surface enhanced Raman
scattering (SERS) and surface enhanced infrared
absorption (SEIRA).
Figure 2. Magnetite on SrTiO3:Nb. a) Atomic Force Microscopy image. The thermal color
height scale corresponds to 40 nm; b) Scanning Tunnelling Microscopy (STM) image acquired
with It=0.7 nA and Vbias= 1 V. The image is 10 nm high; c) STM image acquired with It=0.5 nA
and Vbias= 1.1 V showing the rows of atoms with different orientation in consecutive terraces.
Adapted from Monti et al., 2013.
121
Harmonic
generation
ablation plasmas
in
laser
Our research in this domain focusses on loworder harmonic generation (3th and 5th), of a
probe laser that propagates through the ablation
plume induced by a second laser, as a spatiotemporal diagnostics technique of the different
plume populations. This method has been
applied to carbon containing targets (graphite
and boron carbide) and the nucleobases uracil
and thymine.
We have also tackled investigations of high
harmonic generation (HHG) processes in
ablation plumes using ultrashort femtosecond
pulses as driving fundamental radiation in
cooperation with Prof. J.P Marangos, Imperial
College London and Prof. R.A. Ganeev. We have
compared the efficiency of the HHG process in
atomic and nanoparticle ablation plasmas and
have demonstrated, in the case of metallic
silver-based targets, the noticeable increase of
efficiency in the presence of nanoparticles (Fig.
3). Besides, in the search for nonlinear media
based on ablation plasmas, we have identified
resonance effects in indium plasmas, which are
responsible for the higly efficient HHG.
Figure 3. Comparison of HHG signal of atomic vs nanoparticle ablation plume of silver.
Adapted from Ganeev, Witting et al., 2013.
122
Ultrafast dynamics and control of
molecular processes
Important progress has been made in these
past years both in the real-time observation
of fast photoinduced chemical reactions and in
the subject of intense laser control of reaction
dynamics. These are experiments performed in
the CLUR facility (Center for Ultrafast Lasers)
in collaboration with Prof. Luis Bañares, from
the Complutense University, Madrid. The work
methodology is based on the use of tuneable,
ultrashort laser pulses, in either pump-probe
schemes, or pump-control-probe schemes.
Observation is made through detection of
charged particles in time-of-flight spectrometers
in velocity map imaging configuration, a
technique which offers detailed information on
available energies in the reaction channels and
also on the angular character of the processes
under study.
Regarding the subject of real-time observation of
molecular dynamics, we would like to emphasize
the work done on the bond breaking dynamics
of the carbon-iodine bond in a series of alkyl
iodides, with both linear and branched chains.
This work revealed the crucial role of the radical
structure on the redistribution of energy, and in
its turn, its effect on the reaction dynamics.
In 2013-14 we have contributed with high
impact publications to the field of laser control
of chemical reactions. These describe the
possibility of control of observables like quantum
yields, lifetimes or kinetic energy distributions
in processes of molecular photodissociation.
Control is exerted through the dynamic Stark
effect, the creation of laser-induced conical
intersections and the generation of laser-induced
potentials. As target species, we have selected
methyl iodide, with well-known photodissociation
processes, and for this case we have been able
to show experimentally, as well as simulate
theoretically, how the application of a strong
laser field, with tailored properties, is capable
of changing the “landscape” where the reaction
takes place and thus modify its outcome.
Figure 4. Depiction of laser control of molecular dynamics, represented as the strong
oscillating electric field of the laser acting on the reaction and modifying its outcome. The
background is an Abel-inverted velocity map image of the methyl fragment resulting from UV
dissociation of methyl iodide, under strong field irradiation with an infrared pulse.
123
Laser methods for the conservation
of Cultural heritage
The most relevant result concern the
laser cleaning of pictorial substrates and
biodeterioration layers on stone substrate
s. In the first case we have identified the
physicochemical modifications associated to the
direct laser irradiation of pigments traditionally
used in the artistic painting practise and its
dependence with laser wavelength and pulse
duration, in the nanosecond- femtosecond
range. In the second case we have shown
that IR nanosecond laser pulses serve for the
satisfactory elimination of lichenic coatings on
dolostone samples of built heritage (Fig. 5). On
the other hand, we have succeeded in analysing
and fully characterize degradation pathologies
of historical Roman glasses using laser induced
breakdown spectroscopy (LIBS) in combination
with other more conventional glass analysis
techniques.
Figure 5. SEM-BSE images of Verrucaria nigrescens lichen thalli and microorganisms on
dolostone substrates; a) hydrated control thalli showing algal cells (ac) and chloroplast (c)
(white open arrows and box). The complete laser destruction of algal and fungal cells can
be observed in b) with some fungal lipid body debris (black empty arrows). Adapted from
Speranza et al., 2013.
124
Publications
Oujja, M.; Sanz, M.; Rebollar, E.; Marco,
J.F.; Domingo, C.; Pouli, P.; Kogou, S.;
Fotakis, C.; Castillejo, M. (2013). Wavelength
and pulse duration effects on laser induced
changes on raw pigments used in paintings.
Spectrochim. Acta A 102, 7-14.
Pérez, S.; Rebollar, E.; Oujja, M.; Martín, M.;
Castillejo. M. (2013). Laser induced periodic
surface structuring of biopolymers. Appl.
Phys. A 110, 683-690.
Sanz, M.; Rebollar, E.; Ganeev, R.A.; Castillejo,
M.
(2013). Nanosecond
laser-induced
periodic surface structures on wide band-gap
semiconductors. Appl. Surf. Sci. 278, 325329.
López-Quintás, I.; Oujja, M.; Sanz, M.; Martín,
M.; Ganeev, R.A.; Castillejo, M. (2013). Loworder harmonic generation in nanosecond
laser ablation plasmas of carbon containing
materials. Appl. Surf. Sci. 278, 33-37.
Rebollar, E.; R. Vázquez de Aldana, J.;
Martín-Fabiani, I.; Hernández, M.; Rueda,
D.R.; Ezquerra, T.A.; Domingo, C.; Moreno,
P.; Castillejo, M. (2013). Assessment of
femtosecond laser induced periodic surface
structures on polymer films. Phys. Chem.
Chem. Phys. 15 (27) 11287-11298.
Sanz, M.; Oujja, M.; Rebollar, E.; Marco,
J.F.; de la Figuera, J.; Monti, M.; Bollero, A.;
Camarero, J.; Pedrosa, F.J.; García-Hernández,
M.; Castillejo, M. (2013). Stoichiometric
magnetite grown by infrared nanosecond
pulsed laser deposition. Appl. Surf. Sci. 282,
642-651. Speranza, M.; Sanz, M.; Oujja, M.; de los Ríos,
A.; Wierzchos, J.; Pérez-Ortega, S.; Castillejo,
M.; Ascaso, C. (2013). Nd:YAG laser irradiation
damage to Verrucaria nigrescens. Inter.
Biodeterior. Biodegrad. 84, 281-290.
Hutchison, C.; Ganeev, R.A.; Castillejo,
M.; Lopez-Quintas, I.; Zaïr, A.; Weber, S.J.;
McGrath, F.; Abdelrahman, Z.; Oppermann,
M.; Martin, M.; Lei, D.Y.; Maier, S.A.; Tisch,
J.W.G.; Marangos, J.P. (2013). Comparison
of high-order harmonic generation in uracil
and thymine ablation plumes. Phys. Chem.
Chem. Phys. 15, 12308-12313. Díaz, L.; Camacho, J.J.; Sanz, M.; Hernández,
M.; Jandova, V.; Castillejo, M. (2013). Temporal
evolution study of the plasma induced by CO2
pulsed laser on targets of titanium oxides.
Spectrochimica Acta B. 86, 88-93. Palomar, T.; Oujja, M.; García-Heras, M.;
Villegas, M.A.; Castillejo, M. (2013). Laser
induced breakdown spectroscopy for analysis
and characterization of degradation pathologies
of Roman glasses. Spectrochimica Acta B.
87, 114-120.
Jadraque, M.; Evtushenko, A.B.; Ávila-Brande,
D.; López-Arias, M.; Loriot, V.; Shukhov, Y.G.;
Kibis, L.S.; Bulgakov, A.; Martín, M. (2013).
Co-doped ZnS clusters and nanostructures
produced by pulsed laser ablation. J. Phys.
Chem. C. 117, 5416–5423.
Ganeev, R.A.; Hutchison, C.; Lopez-Quintas,
I.; McGrath, F.; Lei, D.Y.; Castillejo, M.;
Marangos, J.P. (2013). Ablation of nanoparticles
and efficient harmonic generation using 1 kHz
laser. Phys. Rev. A. 88, 033803 (1-10).
Ganeev, R.A.; Witting, T.; Hutchison, C.;
Strelkov, V.V.; Frank, F.; Castillejo, M.; LopezQuintas, I.; Abdelrahman, Z.; Tisch, J.W.G.;
Marangos, J.P. (2013). Comparative studies of
resonance enhancement of harmonic radiation
in indium plasma using multi-cycle and fewcycle pulses. Phys. Rev. A. 88, 033838 (111).
de Buergo, M. A.; Gomez-Heras, M.; Fort,
R.; Ascaso, C.; de los Ríos, A.; Ortega, S. P.;
Sanz, M.; Oujja, M.; Speranza, M.; Wierzchos,
J.; Castillejo, M. (2013). Assessment of
laser treatment on dolostones colonized by
microorganisms and lichens. Science and
Technology for the Conservation of
Cultural Heritage, 173.
Oujja, M.; Sanz, M.; Castillejo, M.; Pouli, P.;
Fotakis, C.; García, A.; Romero, C.; Vázquez
de Aldana, J.R.; Moreno, P.; Domingo, C.
(2013). Effect of wavelength and pulse
duration on laser cleaning of paints. Science
and Technology for the Conservation of
Cultural Heritage, 179.
Palomar, T.; Oujja, M.; Castillejo, M.; Sabio,
R.; Rincón, J. M.; García-Heras, M.; Villegas,
M. A. (2013). Roman glasses from Augusta
Emerita: Study of degradation pathologies
using LIBS. Science and Technology for the
Conservation of Cultural Heritage, 251.
Oujja, M.; García, A.; Romero, C.; R. Vázquez
de Aldana, J.; Moreno, P.; Castillejo, M. (2013).
Analysis of varnish removal on tempera paints
by nanosecond and femtosecond UV lasers, in
Saunders D., Strlic M., Korenberg C., Luxford
N., Birkhölzer K. (Eds.), Proceedings of 9th
International Conference of Lasers in
the Conservation of Artworks, Archetype
Publications, p. 12-18.
125
Monti, M.; Sanz, M.; Oujja, M.; Rebollar,
E.; Castillejo, M.; Pedrosa, F.J.; Bollero, A.;
Camarero, J.; Nemes, N.M.; Mompean, F.J.;
García-Hernández, M.; Nie, S.; McCarty, K.F.;
N´Diaye, A.T.; Chen, G.; Schmid, A.K.; Marco,
J.F.; de la Figuera, J. (2013). In-plane <100>
magnetic easy axis for Fe3O4/SrTiO3(001):Nb
grown by infrared PLD. J. Appl. Phys. 114,
223902 (1-5). Corrales, M.E.; Balerdi, G.; Loriot, V.; de
Nalda, R.; Bañares, L. (2013). Strong field
control of predissociation dynamics. Faraday
Discussions 163, 447-460.
Balerdi, G.; Corrales, M.E.; Gitzinger, G.;
Gonzalez-Vazquez, J.; Sola, I.R.; Loriot, V.; de
Nalda R.; Bañares, L. (2013). Dynamic Stark
shift of the R-3(1) Rydberg state of CH3I. EPJ
Web of Conferences 41, 02035.
Ossi, P.; Castillejo, M.; Zhigilei, L. (Eds.)
(2014). Lasers in Materials Science, Springer
Series in Materials Science, Vol. 191.
Castillejo, M.; Ezquerra, T.A.; Oujja, M.;
Rebollar, E. (2014). Laser Nanofabrication of
Soft Matter, in Lasers in Materials Science,
Springer Series in Materials Science 191,
325-344.
Rebollar, E.; Mildner, J.; Götte, N.; Otto, D.;
Sarpe, C.; Köhler, J.; Wollenhaupt, M.; Baumert,
T.; Castillejo, M. (2014). Microstucturing of
soft organic matter by temporally shaped
femtosecond laser pulses. Appl. Surf.
Sci. 302, 231-235.
Soccio, M.; Alayo, N.; Martín-Fabiani, I.;
Rueda, D.R.; García-Gutiérrez, M.C.; Rebollar,
E.; Martínez-Tong, D.E.; Pérez-Murano, F.;
Ezquerra, T.A. (2014). On the assessment
by Grazing Incidence Small Angle X-ray
Scattering of replica quality in polymer gratings
fabricated by nanoimprint lithography. J.
Appl. Crystal. 47, 613-618.
Lopez-Quintas, I.; Oujja, M.; Sanz, M.;
Benitez-Cañete, A.; Hutchison, C.; de Nalda,
R.; Martin, M.; Ganeev, R.A.; Marangos, J.P.;
Castillejo, M. (2014). Characterization of
laser-induced plasmas of nucleobases: uracil
and thymine. Appl. Surf. Sci. 302, 299-302.
Cueto, M.; Piedrahita, M.; Caro, C.; Martínez
Haya, B.; Sanz, M.; Oujja, M.; Castillejo, M.
(2014). Platinum Nanoparticles as Photoactive
Substrates for Mass Spectrometry and
Spectroscopy Sensors. J. Phys. Chem. C.
118 (21), 11432-11439.
Oujja, M.; Sanz, M.; Castillejo, M. (2014).
Técnicas láser para análisis y conservación
del patrimonio construido. Durabilidad
y conservación de geomateriales del
patrimonio construido, I.S.B.N: 978-84615-7005-8.
Rebollar, E.; Pérez, S.; Hernández, M.;
Domingo, C.; Martín, M.; Ezquerra, T.A.;
García-Ruiz, J.P.; Castillejo, M. (2014).
Physicochemical modifications accompanying
UV laser induced surface structures on
poly(ethylene terephthalate) and their effect
on adhesion of mesenchymal cells. Phys.
Chem. Chem. Phys. 16, 17551-17559.
Diaz, L.; Camacho, J.J.; Cid, J.P.; Martin, M.;
Poyato, J.M.L. (2014). Time evolution of the
infrared laser ablation plasma plume of SiO.
Appl. Phys. A. 117, 125-129.
Corrales, M.E.; González-Vázquez, J.; Balerdi,
G.; Solá, I.R.; de Nalda, R.; Bañares, L. (2014).
Control of ultrafast molecular photodissociation
by laser-field-induced potentials. Nature
Chemistry 6, 785-790.
McGrath, F.; Hawkins, P.; Simpson, E.; Siegel,
T.; Diveki, Z.; Austin, D.; Zair, A.; Castillejo,
M.; Marangos, J.P. (2014). Extending HHG
spectroscopy to new molecular species.
Proc. SPIE 8984, Ultrafast Phenomena and
Nanophotonics XVIII, 89841B.
Gitzinger, G.; Loriot, V.; Bañares, L.; de Nalda,
R. (2014). Pulse shaping control of CH3I
multiphoton ionization at 540 nm. J. Mod.
Opt. 61, 864-871. Loriot, V.; Mendoza-Yero, O.; Pérez-Vizcaíno,
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method using an annular lens array on an
SLM. Appl. Phys. B 117, 67-73.
Corrales, M.E.; Loriot, V.; Balerdi, G.;
Gonzalez-Vazquez, J.; de Nalda, R.; Bañares,
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effects on the ultrafast chemical bond cleavage
of a photodissociation reaction. Phys. Chem.
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dynamics by velocity map imaging: the
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126
COMPETITIVE FUNDING
Ministerio de Ciencia e Innovación
TitleReference
Caracterización y control de nanoestructuras generadas por irradiación láser
Hasta 31/12/2013
CTQ 2010-15680
Javier Aoiz Moleres
Dinámica de procesos químicos: experimentos fotoiniciados con láseres de nanosegundo y
femtosegundo y métodos teóricos
CTQ2008-02578/BQU
TitleReference
Control de Nanoestructuras Generadas por Láser: Interacción Láser-Material y Procesos en el Plasma.
From 01/01/2014
CTQ2013-43086
Member: Rebeca de Nalda Mínguez
IP: Francisco Javier Aoiz
Moleres (UCM, Madrid)
Dinámica de procesos moleculares con
láser y métodos teóricos
From 01/01/2013
CTQ2012-37404-C02-01
Ministerio de Ciencia e Innovación
TitleReference
Cesáreo Sáiz Jiménez, Marta Castillejo Striano (IQFR).
Red Temática de Ciencia y Tecnología para la
Conservación del Patrimonio Cultural
(TechnoHeritage)
HAR2010-11432-E
Ministerio de Educación y Ciencia
TitleReference
Felipe Criado-Boado, Marta Castillejo Striano (IFR-CSIC)
Programa de Investigación en Tecnologías para la
conservación y revalorización del Patrimonio
Cultural (Proyecto Consolider-Ingenio)
CSD2007-00058
Until 31/12/2013
Luis Roso Franco
Ciencia y aplicaciones de los láseres ultrarrápidos
y ultraintensos (Proyecto Consolider Ingenio)
CSD2007-00013,
Until 31/12/2013
127
Consejería de Educación, Juventud y Deporte de la Comunidad Autónoma de Madrid. Programas de Actividades de I+D entre grupos de investigación de la Comunidad de Madrid
TitleReference
Rafael Fort, Marta Castillejo Striano IQFR-CSIC
Durabilidad y conservación de
geomateriales del patrimonio
construido
S2009/MAT-1629,
Until 31/12/2013
Rafael Fort, Marta Castillejo Striano
IQFR-CSIC: Tecnologías y Conservación de
Geomateriales del Patrimonio
S2013/MIT-2914
From 01/10/2014
Participant: Rebeca de Nalda Mínguez. Diseño multiescala de
Coordinator: María Teresa Pérez-Prado
materiales avanzados
(Fundación IMDEA Materiales, Madrid)
DIMMAT, S2013/MIT-
2775
From 01/10/2014
European Synchrotron Radiation Facility
TitleReference
Tiberio Ezquerra
Analysis in situ of Laser Induced Periodic Surface Structures (LIPSS)
Formation on Spin-coated Polymer Films
SC3748
Tiberio Ezquerra
“In situ” monitoring of Laser Induced Periodic Surface Structures on conjugated polymers of
interest in Organic Photovoltaics
SC3977
Swiss Light Source (SLS)
TitleReference
Mari Cruz García-Gutiérrez
Effects of laser induced periodic surface structures on chain alignment and phase
segregation in conjugated polymer blends
Proposal 20140340
International Grants: individual coordinated
European Union
TitleReference
Participant: Rebeca de Nalda Mínguez. IP: Manuel Alcamí (Universidad Autónoma, Madrid)
XLIC: XUV/X-ray light and fast
ions for ultrafast chemistry
From 13/05/2013
(COST Action CM1204)
128
Laser Materials and Interaction
Laser-Materials Group
Doctoral students
Ángel Costela González
(Professor) ReID ORCID SCOPUS
Luis Cerdán Pedraza
(Project Contract until 28/02/2013)
Inmaculada García-Moreno Gonzalo
(Professor)
Mª Eugenia Pérez-Ojeda Rodríguez
(JAE-Pre fellowship until 10/2013)
Clara Gómez Hernández
(Assistant Professor)
Gonzalo Durán Sampedro (FPI fellowship)
Luis Cerdán Pedraza
(Project Contract from 01/03/2013) ReID
Summary
The research of the group continues centered
in the design and development of new photonic
systems
based
on
photosensitized
and
nanostructured materials for advanced devices.
We have continued the study on the processes
that control the synthesis, performance and
properties of both organic and organic-inorganic
hybrid materials with specific properties and
applications in the fields of biomedicine and
optoelectronics. In particular, we have studied
in depth the processes governing the synthesis,
behavior and properties of the new materials in
relation to their structure and nanostructure.
We have designed and synthesized new
molecular dyes, based on BODIPYs, which
have shown optimized laser emission in the
wide spectral region from the blue to the
red. In the field of optoelectronics, we have
demonstrated remarkable improvements in the
laser properties of the new materials when they
incorporate scattering particles of nanometer
size, which under certain conditions improve
the conventional laser action through feedback
non-resonant processes, and that in appropriate
disordered systems give rise to coherent
effects that result in the so-called random laser
emission without the need of using resonant
cavities external to the laser medium. We have
also progressed in the understanding of the laser
operation based on energy transfer processes
where the active molecules are encapsulated
into polymeric nanoparticles contained in
colloidal suspensions. In the field of biomedicine,
we investigate the use of gold nanoparticles
in Photodynamic Therapy and continued our
studies of nanostructured systems for controlled
drug release and on the interaction of laser
radiation with biological tissues.
129
Strategic Aims
• Development of new organic dyes with efficient and stable emisison in the blue, red, and
near infrared spectral regions.
• Development of organic dyes in the red and near IR spectral regions for applications in
photodynamic therapy.
• Design, synthesis and analysis of new photosensitized materials nanostructured by the
incorportion to linear and crosslinked homo- and copolymers of nanometric silica (polyhedral
oligomeric silsesquioxanes, POSS), oxide nanoparticles (TiO2, ZnO) or metal nanoparticles
(gold and silver), both bare or coated with dye-doped polymers or oxide layer (SiO2, TiO2,
ZnO).
• Design, syntjesis and analysis of systems based on processes of energy transfer between
active molecules encapsulated into structured nanoparticles.
• Structural, morphological, optical, photophysical and photochemical characterization of
the synthesized dyes in liquid phase, confined in and covalently bonded to nanoparticles
(polymeric, POSS, metal), incorporated into polymeric matrix (bulk, thin films), and into
nanochannels (zeolite L).
• Characterization of the new materials as laser systems, microlasers, photonic coatings and
random lasers.
• Study of the use of nanostructured systems in biological aplications (photodynamic and
photothermal therapies; controlled release of drugs).
• Development, in collaboration with the company LASING S.A., of commercial laser systems
based on our materials.
• Study of the laser radiation-biological tissue interaction to maximize the applications of the
laser tool in dentistry.
130
Results
Photosensitized and nanostructured
materials for laser applications
During the years 2013 and 2014 we have
continued with the study and development
of nanostructured materials, sensitized with
organic dyes, where the emission properties
are determined by appropriate physical and
structural modifications. We have also delved
in the study of the so-called “random” laser
emission as well as in the processes of energy
transfer (FRET: Förster Resonance Energy
Transfer) between dyes encapsulated into
nanoparticles.
We have obtained new dyes, with emission
covering the spectral range from the blue
to the red by modifications in the core of
dipyrromethene dyes (BODIPYs), either by
replacement of one or both of the fluorine atoms
or by functionalization at the 8 position. We have
also synthesized and characterized cassettes
composed of dyads of new BODIPY-rhodamine
dyes, as well as rosamine dyes with emission at
wavelengths longer than 600 nm. The new dyes
were developed in collaboration with the groups
of Dr. J.L.Chiara (Instituto de Química Orgánica,
CSIC), Prof. Mª José Ortiz (Departamento de
Química Orgánica I, Universidad Complutense de
Fluorescence response of 8-amino BODIPY dyes (solutions in ethyl acetate; excitation
at 366 nm)
131
Madrid), Prof. I. López Arbeloa (Departamento de
Química Física, Universidad del País Vasco), Prof.
K. Burgess (Department of Chemistry, Texas
A&M University, USA), Prof. E. Peña Cabrera
(Departamento de Química, Universidad de
Guanajuato, México), and Prof. Xiao (State Key
Laboratory of Fine Chemicals, Dalian University
of Technology, China).
The laser properties of the new dyes were first
evaluated in liquid solution, to be subsequently
incorporated into various polymeric, hybrid
and/or nanostructured media. Thus, these new
materials were evaluated as laser emitters
in bulk cylindrical matrices (1×1 cm) and in
thin films, as well as in colloidal solution of
nanoparticles containing dye mixtures. We
consistently demonstrated laser efficiencies
higher than in the corresponding commercial
dyes while maintaining high photostability. With
respect to the “random” laser emission, we have
studied the dependence of its properties with
the packing fraction of nanoparticles. We have
also systematically analyzed the FRET assisted
emission in polymeric nanoparticles doped with
dyes in terms of their photophysical and laser
properties, and have used FRET dynamics to
study the diffusion of dyes inside core/shell
nanoparticles.
Finally, we have developed hybrid systems based
on POSS nanoparticles labeled with chromophoric
groups from fluorescent dyes linked to the
inorganic rigid nucleus. These systems of POSS
nanoparticles to which functionalized organic
dyes are covalently linked have demonstrated
to be useful as fluorescent bioprobes.
a) Laser emission of commercial dyes PM567 and PM597 (first and third from the left) and
their derivatives with trifluoroacetoxy groups (to the right of the corresponding commercial
dye) in distributed feedback structured PMMA thin film. b) Output intensity as a function of
pump intensity for PM567 (hollow circles) and its derivative (filled circles).
132
Laser emission of a rosamine dye (structure shown at the right) in ethanol solution as a
function of dye concentration
Efficiency of the laser
emission of different
BODIPY dyes mesosubstituted and
3,5-meso-substituted in
ethyl acetate solution.
The numbers under
the peaks identify the
corresponding dye.
133
Sketch of a waveguide
random laser
A) Normalized laser emission from colloidal suspensions of polymeric nanoparticles doped with
commercial dyes Nile blue and Rhodamine 6G with different relative concentrations. Laser
spectrum in yellow correspond to nanoparticles incorporating just Rh6G. B) Contour plot of
a) laser efficiency (fL), b) laser energy transfer efficiency (fLET), c) FRET efficiency(fFRET), as a
function of both donor and acceptor concentrations.
134
Complementary
application
of
laser radiation in Periodontics and
Orthodontics
Low level laser therapy (or Laser Phototherapy
LP) exhibits a broad range of possibilities for
application in the dental field and specifically in
Periodontics and Orthodontics.
In collaboration with the Department of
Stomatology III (Faculty of Dentistry, UCM,
Madrid), we conducted a study with patients with
chronic periodontitis, evaluating clinical, antiinflammatory and osteoimmunological benefits
of LP applied in repeated doses in combination
with conventional periodontal therapy of scaling
and root planing (SRP), compared with SRP
applied as monotherapy. The results obtained
showed clinical improvement of the disease with
the two types of treatments. Applying adjunctive
LP resulted in improvement of the periodontal
scores, decrease of the IL-1b and TNF-a levels
and a reduction of the RANKL / OPG ratio in the
gingival crevicular fluid (GCF).
In collaboration with the Department of
Stomatology IV (Faculty of Dentistry, UCM,
Madrid), a study with patients suffering from
malocclusion due to severe dental crowding in
the upper arch was carried out. The treatment
involved the extraction of the maxillary second
premolars and placement of fixed multibrackets
and Nance button as an anchorage to achieve
distalization of the maxillary first premolars.
Quadrant 1 received adjuvant treatment with
LP applied in repeated doses. Differences in
pain, speed of the movement of distalation
and RANKL and OPG concentrations in the GCF
between orthodontic treatment and the same
treatment complemented by LP were evaluated.
A decrease in the perception of pain, an increase
in the speed of distalation movement and a slight
increase in values RANKL as consequence of a
high bone resorption due to a fast orthodontic
movement in early stages, were observed after
application of repeated doses of LP.
Periodontal probe composed of a disposable light-diffusing tip covering a stainless steel
autoclave handpiece.
135
Publications
Esnal, I.; Bañuelos, J.; López Arbeloa, I.;
Costela, A.; García-Moreno, I.; Garzón, R.;
Agarrabeitia, A.R.; Ortiz, M.J. (2013). Nitro
and amino BODIPYs: crucial substituents to
modulate their photonic behavior. RSC Adv.
3, 1547-1556.
Cerdán, L.; Costela, A.; Enciso, E.; GarcíaMoreno, I. (2013). Random lasing in selfassembled dye-doped latex nanoparticles:
packing density effects. Adv. Funct. Mater.
23, 3916-3924.
Durán-Sampedro, G.; Agarrabeitia, A.R.;
Cerdán, L.; Pérez-Ojeda, M.E.; Costela,
A.; García-Moreno, I.; Esnal, I.; Bañuelos,
J.; López Arbeloa, I.; Ortiz, M.J. (2013).
Carboxylates versus fluorines: boosting the
emission properties of commercial BODIPYs in
liquid and solid media. Adv. Funct. Mater.
23, 4195-4205.
Esnal, I.; Urías-Benavides, A.; Gómez-Durán,
C.F.A.; Osorio-Martínez, C.A.; García-Moreno,
I.; Costela, A.; Bañuelos, J.; Epelde, N.; López
Arbeloa, I.; Hu, R.; Zhong Tang, B.; PeñaCabrera, E. (2013). Reaction of Amines with
8-MethylthioBODIPY. Dramatic Optical and
Laser Response to Amine Substitution. Chem.
Asian J. 8, 2691-2700.
Gartzia, L.; Yu, H.; Bañuelos, J.; LópezArbeloa, I.; Costela, A.; García-Moreno, I.;
Xiao, Y. (2013). Photophysical and Laser
properties of Cassettes Based on BODIPY and
Rhodamine Pair. Chem. Asian J. 8, 31333141.
Costela, A.; Cerdán, L.; García-Moreno, I.
(2013). Solid state dye lasers with scattering
feedback. Prog. Quantum Electron. 37,
348-382.
Cerdán, L.; Martínez-Martínez, V.; GarcíaMoreno, I.; Costela, A.; Pérez-Ojeda, M.E.;
López Arbeloa, I.; Wu, L.; Burgess, K. (2013).
Naturally Assembled Excimers in Xanthenes
as Singular and Highly Efficient Laser Dyes in
Liquid and Solid Media. Adv. Opt. Mat. 1,
984-990.
Esnal, I.; Valois-Escamilla, I.; Gómez-Durán,
C.F.A.;
Urías-Benavides, A.; BetancourtMendiola, M.L.; López Arbeloa, I.; Bañuelos,
J.; García-Moreno, I.; Costela, A.; PeñaCabrera, E. (2013). Blue-to-orange wavelength
tunable laser emission from BODIPYs tailored
combining meso-substitutions and push-pull
effects. ChemPhysChem. 14, 4134-4142.
Pérez-Ojeda, M.E.; Trastoy, B.; Rol, A.; Chiara,
M.D.; García-Moreno, I.; Chiara, J.L. (2013).
Controlled Click-Assembly of Well.Defined
Hetero-Bifunctional Cubic Silsesquioxanes and
Their Applications in Targeted Bioimaging.
Chem. Eur. J. 19, 6630-6640.
Calderín, S.; García-Núñez, J.A.; Gómez,
C.
(2013).
Short-term
clinical
and
osteoimmunological effects of scaling and root
planing complemented by simple or repeated
Laser Phototherapy in chronic periodontitis.
Lasers Med. Sci. 28(1), 157-166.
Benito, M.; Martín, V.; Blanco, M.D.; Teijón,
J.M.; Gómez, C. (2013). Cooperative effect of
5-aminolevulinic acid and gold nanoparticles
for photodynamic therapy of cancer. J. Pharm.
Sci. 102(8), 2760-2769.
Cerdán, L.; Gartzia-Rivero, L.; Enciso, E.;
Bañuelos, J.; López Arbeloa, I.; Costela, A.;
García-Moreno, I. (2014). Focusing on chargesurface effects to enhance the laser properties
of dye-doped nanoparticles. Laser Phys.
Lett. 11, 015901 (6 pages).
Durán-Sampedro, G.; Esnal, I.; Agarrabeitia,
A.R.; Bañuelos, J.; Cerdán, L.; García-Moreno,
I.; Costela, A.; López Arbeloa, I.; Ortiz, M.J.
(2014). First highly efficient and photostable
E- and C-BODIPYs as dye lasers in liquid
phase, thin films and solid state rods. Chem
Eur. J. 20, 2646-2653.
Cerdán L.; Gartzia-Rivero, L.; Enciso, E.;
López Arbeloa, I.; Costela, A.; García-Moreno,
I. (2014). A FRET analysis of free dye diffusion
in core/shell polymer nanoparticles. RCS Adv.
4, 22115- 22122.
Gartzia-Rivero, L.; Cerdán, L.; Bañuelos, J.;
Enciso, E.; López Arbeloa, I.; Costela, A.;
García-Moreno, I. (2014). Förster Resonance
Energy Transfer and Laser Efficiency in Colloidal
Suspensions of Dye-Doped Nanoparticles:
Concentration Effects. J. Phys. Chem. C 118,
13107-13117.
Martínez-González, M.R.; Urías-Benavides,
A.; Alvarado-Martínez, E.; Cristobal-Lopez, J.;
Gómez, A.M.; del Rio, M.; García, I.; Costela,
A.; Bañuelos, J.; Arbeloa, T.; López Arbeloa,
I.; Peña-Cabrera, E. (2014). Convenient
Access to Carbohydrate-BODIPY Hybrids by
Two Complementary Methods Involving OnePot Assembly of “Clickable” BODIPY Dyes.
Eur. J. Org. Chem. 5659-5663.
Domínguez, A.; Gómez, C.; Palma, J.C. (2014).
Efecto de la radiación láser de baja energía
en la velocidad del movimiento dentario y en
los niveles de RANKL y OPG en pacientes con
tratamiento ortodóncico. Ortod. Esp. 52(2),
9-20.
136
COMPETITIVE FUNDING
TitleReference
Angel Costela González
New photonic systems based on dye-sensitized nanostructured materials for advanced devices.
Design, synthesis and characterization
MAT2010-20646-C04
European Commission Framework Programmes
TitleReference
M.H. Delville, Institut de Chimie de la Matière Condensée de Bordeaux,
Université Bordeaux, Francia
Rational design of hybrid organic-
inorganic interfaces: the next step
towards advanced functional
materials
COST Action MP1202
137
Statistical Mechanics and
Condensed Matter Group
Noé García Almarza
Carl McBride
(01/05/2013 - 01/10/2013)
(Assistant Professor) ReID ORCID
Eva González Noya
Doctoral students
(Assistant Professor) ReID
Cecilia Bores Quijano
Enrique Lomba García
(Professor) ReID ORCID SCOPUS
Claudio Martín Álvarez
Alberto Gallardo Sanz
Vicente Sánchez Gil
(Assistant Professor. Until 10/24/2013)
138
Summary
porous materials, in this latter instance,
including the structural elucidation at the
atomic level of newly synthesized materials.
Our main contributions can be cast into three
main complementary lines: methodology,
systems of fundamental interest, and systems
of experimental interest.
The research carried out for the last two
year focuses on the application of statistical
mechanics and condensed matter theory tools
in conjunction with simulation approaches in
order to analyse problems of physico-chemical
interest, basically in connection to phase
transitions in bulk and under confinement, as
well as adsorption processes in nanostructured
Strategic Aims
• Development of new methodologies for the study of phase transitions.
• Study of phase transitions in complex fluids (water, liquid crystals, anomalous liquids)
• Self-assembly phenomena in simple models.
• Simulation and modelling of adsorption in disordered porous media (carbons, pillared
interlayered clays) and ordered porous media (zeolites).
139
Results
Systems
interactions
with
competitive
Using theoretical and simulation approaches
we have studied phase equilibria in various
systems with competitive interactions (Short
range attractive-long range repulsive). This
sort of interaction gives rise to the formation of
a rich variety of mesophases (patters) at low
temperature: clusters, lamellar phases, … Using
Monte Carlo approaches enabled for the first
time the determination of the complete phase
diagram for a system with these characteristics.
In collaboration with Gerhard Kahl (TUW), these
systems were also studied under confinement in
controlled pore glasses, providing a an explicit
spatial description of the adsorbate structure by
means of a new integral equation approach.
Phase equilibria under confinement
Using Monte Carlo methods, we managed to
determine the phase diagram of a system
with strongly anisotropic interaction (LebwohlLasher model) under confinement. Effects of
confinement and low dimensionality at low
temperatures (where a vapour-liquid transition
is present) and at high temperatures, in which
an isotropic-nematic transition characteristic of
liquid crystals occurs.
Self-assembled
systems
microheterogeneity
and
Another of the main research lines in our group
focuses on the simulation study of self-assembly
processes of anisotropic colloidal particles. Our
aim here is to further our knowledge and in the
last instance predict the most stable crystalline
structures emerging from the self-assembly
process as a function of particle geometry.
This is an extremely relevant topic in materials
engineering for the bottom-up approach to the
design of new materials. By means of crystal
structure optimization procedures and free
energy calculations, our studies in collaboration
with the group of G. Kahl (TUW), have dealt with
particles with heterogenous surface charges.
We have found that this type of topology of the
interactions stabilizes multiple crystalline phase,
including a lamellar phase with interesting
optical and mechanical properties. From a more
theoretical perspective, we have studied in a
joint work with the group of M.M. Telo da Gama
(U. Lisboa) a lattice version of the so called
“Lisbone model” for colloidal particles with
active sites. Using computer simulation we have
determined its phase diagram, which turned out
to exhibit rather exotic topologies: liquid-vapour
equilibria with two critical temperatures, liquid
phases with densities characteristic of a vapour
phase, etc … Additionally, in collaboration
with the group of Marcia Barbosa (UFRGS),
Aurélien Perera (UPMC) and Diego Salgado
(U. Vigo), we have started a full scale study of
mixtures alcohol/water, in order to characterize
thermodynamic and structural singularities, as
well as the topology of the microheterogeneous
structures, which can be thought as precursors
of micellar systems. In line with these studies
on microheterogeneity, we have also initiated
a work in collaboration with Lev Sarkisov (U.
Edinburgh) on ionic liquids under confinement,
which represent promising materials both in
the field of energy storage and carbon dioxide
capture.
Adsorption in disordered porous
materials
In 2014 we publish an extensive work (Gallardo
et al., 2014) in which we have collected all our
experimental work -from adsorption experiments
in collaboration with J.M. Guil (IQFR), J.Pires
(U. Lisboa) D, to neutron scattering experiments
(C. Cabrillo, IEM)- and simulation studies to
investigate the behaviour of probe molecules
adsorbed into pillared interlayered clays (PILCS).
Our simulation results enable the interpretation
of the anomalous behaviour of some of the
samples studied. The core of this work was
an essential part of the PhD thesis of Alberto
Gallardo (defended in February 2015). Also, in
collaboration with J.M. Guil, we have carried
adsorption experiments of aromatic molecules,
noble gases and methane into pure silica ZSM11.
He it was detected for some of the compounds
anomalous jumps in the adsorption volumetric
and calorimetric curves (approximately at half
filling). In order to get a microscopic insight into
the origin of this behaviour, we have carried
synchrotron X ray diffraction experiments at the
ALBA facility (Barcelona) and neutron scattering
experiments art he ISIS facility (Didcot, UK).
Analysis of the diffraction patterns with an in-
140
house designed Reverse Monte Carlo code,
together with Grand Canonical Monte Carlo
simulations of the adsorption isotherms, indicate
that the flexibility of the zeolite plays a crucial
role in the adsorption process. The jump in the
adsorption curves could then be interpreted as
a result of an spatial reordering of the adsorbate
as a consequence of the flexibility of the zeolite
framework during the loading process.
Figure 1. Neutron diffraction experiments of argon and methane adsorption into a ZSM11
zeolite carried at the ISIS facility (Dicot, UK).
141
Figure 2. Density map illustrating clustering effects for a system with
competing interactions adsorbed in a controlled pore glass.
Figure 3. Clustering of [1-butyl, 3-metyl imidazolio]+ cations and
[PF6]- inside a graphitic carbonaceous material.
142
Publications
Aragones, J.L.; Noya, E.G.; Valeriani, C.;
Vega, C. (2013). Free energy calculations for
molecular solids using GROMACS. J. Chem.
Phys. 139, 034104.
Ashton, D.J.; Sánchez-Gil, V.; Wilding,
N.B. (2013). Monte Carlo methods for
estimating depletion potentials in highly sizeasymmetrical hard sphere mixtures. J. Chem.
Phys. 139, 144102.
McBride, C.; Noya, E.G.; Vega, C. (2013).
A computer program to evaluate the NVM
propagator for rigid asymmetric tops for use
in path integral simulations of rigid bodies.
Comp. Phys. Comm. 184, 885-890.
Pokalski, J.; Ciach, A.; Almarza, N.G. (2013).
Periodic ordering of clusters in a onedimensional lattice model. J. Chem. Phys.
138, 144903.
Lomba, E. (2014). Simple water-like lattice
models in one dimension. Trans. R. Norw.
Soc. Sci. Lett. 3, 63-74.
Almarza, N.G.; Pokalski, J.; Ciach, A. (2014).
Periodic ordering of clusters and stripes in a
two-dimensional lattice model. II. Results of
Monte Carlo simulation. J. Chem. Phys. 140,
164708.
Gallardo, A.; Guil, J.M.; Lomba, E.; Almarza,
N.G.; Khatib, S.J.; Cabrillo, C.; Sanz, A.; Pires,
J. (2014). Adsorption of probe molecules in
pillared interlayered clays: Experiment and
computer simulation. J. Chem. Phys. 140,
224701.
Lomba, E.; Bores, C.; Kahl, G. (2014). Explicit
spatial description of fluid inclusions in porous
matrices in terms of an inhomogeneous integral
equation. J. Chem. Phys. 141, 164704.
Lomba, E.; Høye, J.S. (2014). Critical region of
D-dimensional spins: extension and analysis of
the hierarchical reference theory. Mol. Phys.
112, 2892–2905.
Gonzalez, M.A.; Sanz, E.; McBride, C.;
Abascal, J.L.F.; Vega, C.; Valeriani, C. (2014).
Nucleation free-energy barriers with Hybrid
Monte-Carlo/Umbrella
Sampling.
Phys.
Chem. Chem. Phys. 16, 24913.
Mompeán, M.; González, C.; Lomba, E.;
Laurents, D.V. (2014). Combining Classical
MD and QM Calculations to Elucidate Complex
System
Nucleation:
A
Twisted,
Three
Stranded, Parallel β-sheet Seeds Amyloid Fibril
Conception. J. Phys. Chem. B. 118, 7312.
Pokalski, J.; Ciach, A.; Almarza, N.G. (2014).
Periodic ordering of clusters and stripes in
a two-dimensional lattice model. I. Ground
state, mean-field phase diagram and structure
of the disordered phases. J. Chem. Phys.
140, 114701.
Sánchez-Gil, V.; Noya, E.G.; Lomba, E. (2014).
Reverse Monte Carlo modeling in confined
systems. J. Chem. Phys. 140, 024504.
Tavares, J.M.; Almarza, N.G.; da Gama, M.M.T.
(2014). Three-dimensional patchy lattice
model: Ring formation and phase. J. Chem.
Phys. 140, 044905.
Almarza, N.; Martín, C.C.; Lomba, E. (2014).
Phase behaviour of the confined lattice gas
Lebwohl-Lasher model. Condens. Matter
Phys. (Ukraine). 16, 43602.
143
COMPETITIVE FUNDING
TitleReference
Theory and simulation in complex systems
FIS2013-47350-C5-4-R
Enrique Lomba Garcia
Physical processes under confinement: adsorption, self-assembly and phase transitions
FIS2010-15502
Comunidad de Madrid
TitleReference
Enrique Lomba Garcia
Modelling and simulation in complex systems: MODELICO-CM.
S2009ESP-1691
CSIC/CNPQ
TitleReference
Anomalous behavior and emerging
structures in self-assembly systems
2011BR0046
144
Surface Analysis and Mossbauer
Spectroscopy Group
Doctoral students
José Francisco Marco Sanz
(Associate Professor) ReID ORCID
Matteo Monti (until 01/09/2014)
Laura Martín García (from 01/01/2014)
Technical Staff
Carlos Alonso González
Raquel Gargallo
(Contract from 01/03/2014)
145
Summary
The scientific activity of this research group
focuses on the study and characterization
of surface processes of very different
nature through the use of microscopy and
spectroscopy techniques in ultrahigh vacuum
(including nanospectroscopic techniques based
on synchrotron radiation). In particular, in
the period 2013-2014 our interest has been
centered on the study of the growth dynamics of
thin films of oxides on different substrates and
the study of surface and interfacial magnetism.
Another important line of research of this
group is the chemical, structural and magnetic
characterization of transition metal oxides with
different structures (spinel, perovskite...) and
with potential applications in the field of energy
conversion and storage. A notable aspect of our
activity is the construction of instrumentation for
surface analysis. We note that this group is one
of the few spanish groups that has full Mossbauer
spectroscopy capabilities in its different modes
(transmission, integral conversion electron,
integral low energy electron), and that is the
reference group in Spain for low-energy electron
microscopy (LEEM), performed in collaboration
with the groups of Lucia Aballe (Alba synchrotron,
Barcelona), Kevin F. McCarty (Sandia National
Laboratories, USA) and Andreas K. Schmid
(Berkeley National Laboratory, USA).
Strategic Aims
• Understanding the dynamics and growth mode of thin films (a few atomic layers thick) of
metal oxides on metal and oxide substrates. Determination of the structural and magnetic
properties of these films.
• Modification of the magnetic properties of thin films of metal oxides by changing their growth
parameters. Eventually, the design of devices and sensors based on the modification of these
properties.
• Determination of the influence that the stoichiometry and the method of preparation have
on the cation distribution and the magnetic properties of complex transition metal oxides.
• Construction and implementation of instrumentation for surface analysis.
146
Results
Controlling the growth of high quality
thin films and heterostructures
Work has been carried out to determine the
conditions for growing high quality thin and
ultrathin films of various oxides. This has been
performed combining many different growing
techniques.
Molecular beam epitaxy (MBE-O2) and
oxidation of metallic films (MBE + O2)
The MBE growth experiments have been
carried out both at the XPS/STM/LEED system
of the group in Madrid, and at several LEEM
microscopes. In the former case, an auxiliary
UHV chamber for sample preparation has been
mounted on the main system. In that chamber,
iron oxides have been grown on Ru either by
deposition of iron in an oxygen atmosphere
(MBE-O2) or by Fe deposition in UHV followed by
a subsequent step of oxidation of the deposited
metal film in an oxygen atmosphere (MBE+O2).
In the latter case, we have started to explore
the phase space of mixed Co and Fe oxides on
Ru (0001) determining that, in the initial stages,
the growth proceeds through the formation of
one or two layers of an Fe-Co mixed monoxide,
and that, in a later stage, three-dimensional
islands of a spinel phase appear.
Electron gun evaporation (evapE)
In collaboration with Dr. P. Prieto from the
Department of Applied Physics of the UAM, and
within the current research project, we have
grown thin iron oxide films by evaporating
iron metal in a reactive atmosphere varying
the O2 partial pressure, substrate temperature
(300-400ºC) and the growth rate. We have obtained
nonstoichiometric Fe3O4 films on glass and
MgO substrates which show biaxial magnetic
anisotropy. It has been confirmed that the
assistance with ions during the growth process
produces amorphization of the films.
Ion beam assisted deposition by reactive
sputtering (sputt-O2)
Also in collaboration with the group of P. Prieto
we have grown and characterized thin iron
oxides films made by reactive sputtering from
a metallic Fe target. We have also grown films
with the assistance of a second beam of ions
with variable ion energy and O2+ content. We
used three types of substrate: MgO, glass and
Si wafers, and temperatures > 300 ° C. We
have optimized the growth conditions to obtain
films with biaxial magnetic anisotropy on MgO
substrates, what is characteristic of epitaxial
growth. Apart from iron oxides, we have also
tried the growth of cobalt ferrite films carrying
out a comparative study of the use of a CoFe2
metal target and an insulator target of CoFe2O4.
We have found that the use of a “buffer” layer
of TiN optimizes the crystal growth on Si, which
enables the integration of magnetite in Si-based
devices. We have started the growth of thin
films of BiFeO3 as well as oxide/metal (CoFe2O4/
CoFe2) and oxide/oxide (CoFe2O4/ Fe3O4) bilayers
on silicon substrates.
Growth by pulsed laser deposition (PLD)
In collaboration with the group of M. Castillejo
of the IQFR we have added a PLD growth
chamber directly connected to the main surface
characterization system of our lab. We have grown
up to 20 nm thick layers of monocrystalline FeO
having a low vacancy concentration, something
which is quite unusual in the bulk form of FeO.
Sol-Gel (SLG)
In collaboration with the Surface Science Group of
the UCM we have synthesized and characterized
Fe oxide nanoparticles embedded in a silica
thin film grown on a Si substrate. Experimental
evidence has been obtained for the synthesis
of hematite (α-Fe2O3), maghemite (γ- Fe2O3),
β- Fe2O3 and magnetite (Fe3O4). The β phase
is a rare Fe3+ oxide polymorph being this the
first time that has been synthesized by sol-gel
techniques and its Raman spectrum identified.
We are working on optimizing the conditions to
favor the β single-phase synthesis, trying to grow
thinner and more homogeneous layers than the
current ones. Remarkably so, we want to state
that we have optimized the synthesis of ε-Fe2O3
particles, a metastable phase volume, in a silica
matrix on Si substrates, obtaining samples
with a low concentration of other phases. The
particles are nano-sized as well as (and this is
unusual for this phase) micrometric allowing
therefore its detailed characterization by Raman
spectroscopy.
147
Figure 1. Surface analysis system with the new chamber to prepare samples by PLD
Structural, electronic and magnetic
properties of oxide surfaces both
from thin films and bulk single
crystals. Thickness and surface
effects
An important part of the work has been directed
to identify the phases of Fe oxides obtained
by the techniques described in the previous
section, as well as to study the behaviour of
magnetite surfaces of bulk crystals. Mössbauer
spectroscopy has been applied to films made
by all methods as well as to complex oxides of
the perovskite family (this work in collaboration
with the Department of Chemistry, University of
Birmingham, UK).
The Fe (Fe-Co) oxide films grown by MBE-O2,
MBE+O2 have been specifically studied by STM,
LEED, XPS,LEEM, PEEM and XMCD. This has
allowed to identify that the films correspond to
Fe3O4 (Fe3-xCoxO4) islands onto a FeO (FexCo1-xO)
layer. By LEEMwe have investigated the influence
of the Fe flux and oxygen pressure in MBE-O2grown oxides, finding a strong dependence on
the relative composition and morphology of the
FeO/Fe3O4 combination. In the case of cobaltiron mixed oxides, we have detected polarization
circular dichroism of magnetic origin in the
oxygen atoms, and we have measured the spin
and orbital magnetic moments of both the Fe and
the Co atoms of the oxides. A study combining
MFM ex-situ and XMCD-PEEM in-situ in the same
micrometric islands is currently under way.
Finally, we have characterized CoFe2O4 thin films
on TiN / Si (100), and determined its degree of
148
crystallinity by channeling in RBS. These layers
show a surprisingly high coercive field> 6KOe.
Characterization of magnetite films grown by
evapE has been carried out by XRD. MOKE
and reflectance, transmittance, resistivity
and, in some samples, Seebeck coefficient
measurements. We have observed a correlation
between the lattice parameter, coercive field
and the Seebeck coefficient in evapE / glass
and n-type conductivity. Characterization of
films grown by sputt-O2 has been ccarried out
by MOKE, XRD, and resistivity measurements.
We have correlated the low O2 content in the
assistance beam with the existence of tensions
in the magnetite films. The SLG / glass samples
were characterized by XRD, Raman spectroscopymicroscopy, AFM and magnetic measurements,
Mössbauer, SQUID and VSM.
Special attention has been paid to the study
of the magnetic anisotropy of magnetite,
comparing the results obtained on single crystal
samples with those obtained on the thin films.
The films exhibit properties usually assigned to
the presence of antiphase boundaries, as well as
a biaxial symmetry along the easy magnetization
axes within the plane of the film. This has been
determined by MOKE and, in some cases, FMR and
SPLEEM. These directions do not match neither
those of the volume nor those most frequently
reported by other groups in thin films. Besides,
polycrystalline samples grown by sputt-O2 on
Si have no anisotropy, whereas those grown on
glass show uniaxial magnetic anisotropy within
the plane. We are currently studying the origin
of these discrepancies, in order to control the
magnetic anisotropy in applications. Given the
dominant role of antiphase boundaries in the
magnetic properties of iron and iron-cobalt spinel
films, it is highly relevant to be able to grow
crystals or films free of antiphase-boundaries.
In this area we are using the combination of
MBE-O2 growth with real time observation of the
growth front by LEEM microscopy to obtain films
with well defined microstructure that includes
highly perfect spinel 3-dimensional islands with
lack antiphase boundaries as each island arises
from a single nucleation event.
For reference purposes, and also due to their
intrinsic interest, we have caracterized the
surface of magnetite bulk single crystals, in
particular the (100) orientation. We have
observed the ferroelastic Verwey transition on
the magnetite surface for the first time, and we
have discovered a novel surface order-disorder
transition at high temperatures. Exposure to
oxygen at high temperatures produces the
formation of more magnetite at the surface,
while oxidation takes place at macroscopically
separared regions. This effect has implications
in the use of magnetite as a catalyst. Finally,
we have measured the magnetic moment at
the surface together with the micromagnetism
by XMCD-PEEM and SPLEEM, respectively. In
the first case, the observation of a reduced
spin moment is explained in terms of a surface
reconstruction, and has been reported in the
first publication of the LEEM/PEEM station of
the Alba synchrotron. In the second case, the
surprising finding of the temperature evolution
of the magnetic domains has been related with
the strong changes in the magnetocrystalline
anisotropy of magnetite, and its competition
with the shape anisotropy.
149
Publications
de la Figuera J.; McCarty K.F. (2013). Lowenergy electron microscopy, in Surface
Science Techniques, Eds. G. Bracco and B.
Holst, Springer Series in Surface Sciences,
51, 531.
de la Figuera J.; Vergara L.; N’Diaye,
A.T; Quesada A.; Schmid, A. K. (2013).
Micromagnetism in (001) magnetite by spinpolarized low-energy electron microscopy.
Ultramicroscopy 130, 77-81.
Gautier, J.L.; Monrás, J.P.; Osorio-Román, I.O.;
Vásquez, C.C.; Bravo, D.; Herranz, T.; Marco,
J.F.; Pérez-Donoso, J.M. (2013). Surface
characterization of GSH-CdTe quantum dots.
Mat. Chem. Phys. 140, 113-118.
Alcázar, G.A.P.; Zamora, L.E.; Tabares, J.A.;
Piamba, J.F.; González, J.M.; Grenèche , J.M.;
Martínez, A.; Romero J.J.; Marco, J.F. (2013).
Evidence of magnetic dipolar interaction
in micrometric powders of the Fe50Mn10Al40
system: melted alloys. J. Magn. Magn.
Mater. 327, 137-145.
Whitaker, M.J.; Marco, J.F.; Berry, F.J.; Taith,
C.; Blackburn, E.; Greaves, C. (2013).
Structural and magnetic characterisation of
the pryrochlores Bi2-xFex(FeSb)O7, (x=0.1,
0.2, 0.3), Nd1.8Fe0.2(FeSb)O7 and Pr2(FeSb)
O7. J. Solid State Chem. 198 316-322.
Prieto, P.; de la Figuera, J; Sanz, J.M.;
Marco, J.F. (2013). Effects of low energy ion
bombardment on the formation of cubic iron
mononitride thin films. Thin Solid Films 539,
35-40.
Oujja, M.; Sanz, M.; Rebollar, E.; Marco, J.F.;
Castillejo, M.; Domingo, C.; Pouli, P.; Kogou,
S.; Fotakis, C. (2013). Wavelength and pulse
duration effect on laser induced changes on
raw pigments used in paintings. Spectrochim.
Acta A: Mol. Biomol. Spec. 102, 7-14.
Gurushinge, N.N.M.; de la Figuera, J.; Marco,
J.F.; Thomas, M.F.; Berry, F.J.; Greaves, C.
(2013). Synthesis and characterisation of the
Ruddlesden-Popper phases Ln2Sr(Ba)Fe2O7
(Ln=La, Nd, Eu). Mater. Res. Bull. 48, 35373544.
Sanz, M.; Oujja, M.; Rebollar, E.; Marco,
J.F.; de la Figuera, J.; Monti, M.; Bollero,
A.; Camarero, J.; Pedrosa, F.J.; GarcíaHernández, M.; Castillejo, M. (2013).
Stoichiometric magnetite grown by infrared
nanosecond pulsed laser deposition. Appl.
Surf. Sci. 282, 642-651.
Palacio, I.; Monti, M.; Marco, J.F.; McCarty
K.F.; de la Figuera, J. (2013). Initial stages of
FeO growth on Ru (0001). J. Phys.: Condens.
Matter 25, 484001.
Marco, J.F.; Gancedo, J.R.; Monti, M.; de la
Figuera, J. (2013). Mössbauer spectroscopy
and
surface
analysis
en
Mössbauer
Spectroscopy: Applications in Chemistry,
Biology and Nanotechnology, First edition.
Cap. 22, pp. 455-469. V.K. Sharma, G.
Klingelhofer y T. Nishida, eds. John Wiley &
Sons.
Nie, S.; Starodub, E.; Monti, M.; Siegel, D.A.;
Vergara, L.; El Gabaly, F.; Bartelt, N.C.; de la
Figuera, J.; McCarty, K.F. (2013). Insight into
Magnetite’s Redox Catalysis from Observing
Surface Morphology during Oxidation. J.
Amer. Chem. Soc. 135, 10091-10098.
Monti, M.; Sanz, M.; Oujja, M.; Rebollar, E.;
Castillejo, M.; Pedrosa, F. J.; Bollero, A.;
Camarero, J.; Cuñado, J.L.F.; Nemes, N.M.;
Mompean, F.J.; Garcia-Hernandez, M.; Nie,
S.; McCarty, K.F.; N’Diaye, A.T.; Chen, G.;
Schmid, A.K.; Marco, J.F.; de la Figuera, J.
(2013). Room Temperature In-plane <100>
Magnetic Easy Axis for Fe3O4/SrTiO3(001):Nb
Grown by Infrared pulsed laser deposition. J.
App. Phys. 114, 223902.
Siegel, D.A.; Chueh, W.C.; El Gabaly, F.;
McCarty, K.F.; de la Figuera, J.; Blanco-Rey,
M. (2013). Determination of the structure of
CeO2(111) by low-energy electron diffraction.
J. Chem. Phys. 139, 114703.
de la Figuera, J.; Novotny, Z.; Setvin, M.; Liu,
T.; Mao, Z.; Chen, G.; N’Diaye, A.T.; Schmid,
M.; Diebold, U.; Schmid, A.K.; Parkinson, G.S.
(2013). Real Space Imaging of the Verwey
Transition at the (100) Surface of Magnetite.
Phys. Rev. B 88, 161410.
Porras-Vázquez, J.M.; Pike, T.; Hancock, C.A.;
Marco, J.F.; Berry, F.J.; Slater, P.S. (2013).
Investigation into the effect of Si doping on
the performance of SrFeO3-δ SOFC electrode
materials. J. Mater. Chem. A 1, 1183411841.
150
Alfonso, J.E.; Olaya, J.J.; Pinzón, M.J.; Marco,
J.F. (2013). Potentiodynamic polarization
studies and surface chemical composition of
bismuth titanate (BixTiyOz) films produced
through radiofrecuency magnetron sputtering.
Materials 6, 4441-4449.
Alfonso, J.E.; Cárdenas, M.; Marco, J.F.
(2013). Influence of fabrication paameters
on crystallization, microstructure, surface
composition, and optical behavior of MgO thin
films deposited by rf magnetron sputtering. J.
Supercond. Nov. Magn. 26, 2463-2466.
Cubillos, G.I.; Olaya, J.J.; Bethencourt, M.;
Cifredo, G.; Marco, J.F. (2013) “Producción
y caracterización de películas de óxido de
circonio por espray pirólisis”. Rev. LatinAm.
Metal. Mat. 33, 116-130.
Berry, F.J.; de Laune , B. P; Greaves, C.;
Whitaker, M.J.; Thomas, M.F.; Marco, J.F.
(2014). “Mössbauer spectroscopy in the
investigation of new mineral-related materials”.
Hyperfine Interact. 226, 545-552.
Alburquenque, D.; Vargas, E.; Denardin, J.C.;
Escrig, J.; Marco, J.F.; Ortiz, J.; Gautier, J.L.
(2014). “Physical and electrochemical study of
cobalt oxide nano- and microparticles”. Mat.
Charac. 93, 191-197.
Gurushinge,
N.N.M.; Fones, J.C.; Marco,
J.F.; Berry, F.J.; Greaves, C. (2014). “Fluorine
insertion in the Ruddlesden-Popper phase
La2BaFe2O7: the structure and magnetic
properties of La2BaFe2O5F4”, Dalton Trans.
43, 2038-2043
Garrido-Ramirez,
E.G.;
Mora,
M.L.;
Marco, J.F.; Ureta-Zañartu, M.S. (2013).
“Characterization of nanostructured allophane
clays and their use as support of iron species
in a heterogeneous electro-Fenton system”.
Applied Clay Science 86, 153-161.
McCarty, K. F.; Monti, M.; Nie, S.; Siegel, D.A.;
Starodub, E.; El Gabaly F.; McDaniel, A. H.;
Shavorski, A.; Tyliszczak, T.; Blum, H.; Bartelt,
N.C.; de la Figuera, J. (2014). “Oxidation of
Magnetite (100) to Hematite Observed by Insitu Spectroscopy and Microscopy”, J. Phys.
Chem C. 118, 19768-19777.
Bartelt, N.C; Nie, S.; Starodub, E.; Bernal,
I.; Gallego, S.; Vergara, L.; McCarty, K.F.; de
la Figuera, J. (2013). “Order-disorder phase
transition on the (100) surface of magnetite”
Phys. Rev. B 88, 235436.
Gómez-Ferrer, B.; García-Cortés, I.; Marco, J.F.;
Jiménez-Rey, D.; Vila, R. (2014). “Decoupling
of defect and short range order contributions
to resistivity recovery measurements in binary
alloys”. Phys. Rev. B 90, 220102 (R).
Cubillos, G.I.; Bethencourt, M.; Olaya, J.J.;
Alfonso, J.E.; Marco, J.F. (2014). “The influence
of deposition temperature on microstructure
and corrosion resistance of ZrOxNy/ZrO2
coatings deposited using RF sputtering” App.
Surf. Sci. 309, 181-187.
Quesada, A.; Rubio-Marcos, F.; Marco,
J.F.; Mompean, F.J.; García-Hernández,
M.; Fernández, J.F. (2014). “On the origin
of remanence enhancement in exchangeuncoupled CoFe2O4-based composites”. Appl.
Phys. Lett. 105, 202405.
151
COMPETITIVE FUNDING
TitleReference
Juan de la Figuera
Ultrathin films for oxides-based electronics. Real time growth, interface effects and magnetism
MAT2012-38045-C04-01
152
Research Support Services
Chromatography and Mass Spectrometry Service
155
Library 159
Management and Administration
170
Stockroom
170
Reception
170
Technical Support Units
172
• Electronics Workshop
172
• Mechanics Workshop
172
• Glassblowing Workshop
172
• Computer Support
172
• Building Maintenance
172
Scientific Report 2013/2014 Research Support
153
Services
Chromatography and Mass
Spectrometry Service
Chromatography and Mass
Scientific Director
Technician
Rosa Lebrón Aguilar
Asunción de Diago Gómez
(Research Assistant) (retired in October 2014)
Technical Director
Plácido Galindo Iranzo
(Specialized Technician)
Introduction
The Chromatography and Mass Spectrometry
Laboratory of the Institute of Physical Chemistry
“Rocasolano” has been working since 2002.
During this time, different mass spectrometers
have allowed to analyze a large number of
substances, ranging from small molecules to
proteins and polymers. In the biennium 20132014, a matrix assisted laser desorption/
ionisation-time of flight mass spectrometer
(MALDI-TOF), model Voyager-DE PRO (Applied
Biosystems), has been available.
The Laboratory work is mainly focused on the
determination of molecular masses by MALDITOF of molecules with masses ranging from
1,000 to 300,000 u, especially intact proteins.
The analyses are carried out by qualified
technical personnel belonging to the IQFR, and
the detailed rules of operation are collected
on the web site of the Laboratory (http://
serviciomasas.iqfr.csic.es/).
Scientific Report 2013/2014 Chromatography and Mass
156
Strategic Aims
• Supporting tool for the research carried out by the different Departments of the IQFR, as well
as external users.
• Integrate and adapt existing mass spectrometric methodologies to the specific needs of our
users.
Results
During the period 2013–2014, a total of 664
analyses have been carried out, almost the
same number of samples than in the previous
biennium. Of these analyses, 89% have been
performed for the various departments of
the IQFR, and the rest of them, for other
CSIC institutes (Institute of Polymer Science
and Technology, Institute of General Organic
Chemistry, Institute of Medicinal Chemistry,
and Institute of Food Science, Technology and
Nutrition).
As usual, analyses to confirm the molecular
mass (before and after different treatments)
of proteins, peptides, carbohydrates, colorants
and silsesquioxane, among others, have been
carried out. In particular, off-line monitoring
of the degradation of muropeptides and
oligosaccharides involved in hydrolysis protein
reactions has been the most demanded.
Synthetic polymers have also been studied by
the standard procedures, in order to determine
their molecular mass distributions, repetitive
units and terminal polymer groups
Finally, the Service has continued organizing,
preparing and giving three courses on “Liquid
Chromatography coupled to Mass Spectrometry”
(26 h/course) within the Training Program of
the CSIC, which highlights our commitment to
education and training.
Figure 1: MALDI plate with some sample preparations using 2,5-DHB matrix. The left image
shows part of spot 63 as seen on the TV screen of the ion source observation optics.
Scientific Report 2013/2014 Chromatography and Mass
157
Library “biqfr”
Introduction
The Rocasolano Institute of Physical Chemistry
was set up in 1946 at same time as the Biqfr.
Its holdings come from the “National Institute
of Physics and Chemistry” created in 1932.
Commonly known as the Rockefeller Institute,
it was the cradle of all the research teams in
the different disciplines of Chemistry, not only in
Madrid, but throughout Spain. Three elements
characterize the Biqfr: its Collection, Space and
Management.
Collection: Among these old collections -unique
in Spain- can be found famous titles such
as: Annalen der Physik, Chemische Berichte,
Annalen der Chemie. These are scientific
journals in which the first advances in physics
and chemistry are recorded. The Biqfr holds a
valuable holding, mainly journals, of which 113
are complete starting from the first issue, 11
date from the 19th century to our days, and 16
start prior to 1920.
Einstein, A. (1905). Ist die Trägheit
eines Körpers von seinem Energieinhalt
abhängig? Ann. Phys. 18, 639-641. (The
equation E=mc2).
Space: Designed by the architects M. Sánchez
Arcas and L. Lacasa (1932), innovators at the
time, the library is arranged longitudinally with
the rest of the building. It has an easy access
from the main entrance and faces South with
three large windows illuminating the two floors
containing the reading room. This provides
a silent and conducive reading environment,
according to the architect Antonio Bonet Correa.
The floors were communicated inside with
original spiral staircase of the “flown boat” style,
which was recently replaced by another wooden
one. Subsequently, a basement has been added
and their rooms refurbished, while retaining the
original style. Because of its singular interest
the library is the subject of visits by architects
from various universities.
Management: At its genesis, the Biqfr was
organized in a way that was revolutionary for
those days, free access was permitted, and
display stands facilitated access to the latest and
the previous year’s issues of the journals. The
main goal has always been the satisfaction of its
users. The Biqfr is considered by the scientific
community as the Reference Scientific Periodical
Library, a historical landmark in the service of
innovation, and is obviously one of the most
outstanding scientific libraries in Europe. It is a
rare example of 80 years of continuous service
to Spanish researchers.
Scientific Report 2013/2014 Library “Biqfr”
160
Library “Biqfr”
Library Manager
Assistant
Esperanza Iglesias Fernández
Santiago del Olmo Rodríguez
Technicians
Jorge Pariente Moronta
Adoración Urrea Salazar
Ángel González González (until 01/03/2104)
Ángel Alonso Fernández (until 09/2013)
Strategic Aims
• New technologies.
• Access to knowledge.
• Supply Documents.
• Economic implication.
• Standard management.
• Special activity.
161
Results
New technologies
Since the beginning of technological age, in
the 90s, the Biqfr has been aware that the
technological changes, that were happening so
quickly, provide an opportunity to the library
to link it to the concept value. In recent years,
this concept has been the mainstay of technical
work to ensure that the library is competitive,
proactive and even co-creative. By knowing the
researchers’ perception of the library in relation
to the alternatives offered by its competitors
(eg. Google), the Biqfr has developed links with
scientists, to help researchers achieve their
goals. Because of this, the Biqfr has an edge on
its competitors.
Let’s put it on a timeline!
162
The Blog & Social Networks
Our blog remains a key tool for dissemination
and visibility. It posts news from all areas
of science and innovation. In the period
2013-2014, there have been changes in the
editorial line to promote and disseminate the
activities developed in IQFR: Seminars series,
conferences, activities of the Center and the
Biqfr. Always with the same purpose: trying to
democratize “Science” and bring it to the public
in a fun and an entertaining way.
The interest of our blog’s followers remains
constant. During 2013-2014, 600 news items
were published: an average of 2 per day! During
this biennium, we achieved 257,369 visits to
reach a total of 1,400,000 visits. The activity of
our followers on the social networks Twitter and
Facebook is constant and stable, as is the case
with the Blog.
The Biqfr Blog is not only considered a scientific
dissemination source in America (Mexico,
Colombia, United States and Argentina) and
Germany, but we have also detected that it
begins to attract followers from other European
countries (Russia, France, Switzerland &
Ukraine) and even in Lebanon.
Access to knowledge
Over the last two years, a main goal has been
the implementation of a smart tool to accelerate
the search for scientific information, providing
a competitive advantage to Biqfr over Google,
while saving the user time and mouse clicks.
Customization functionality has achieved a tool
on demand: iLumina.
163
All specialized databases in the fields of
Chemistry, Physics and Biomedicine, to which
users of the Biqfr have access, are brought
together. Through a single search box, with oneclick access to PDF or HTML, the user can access
full-text content directly through the detailed
record or from the result list preview pane.
The AtoZ resource manager, can be utilized
independently or through the iLumina system,
where it is now incorporated.
iLumina leverages with discovery technology
(EBSCO Discovery EDS) employing a multifaceted
relevance
ranking
methodology,
moreover setting up a unified index with all the
Biqfr information resources to offer their users
an easy and powerful access to the Biqfr holdings
with a single search interface. Metadata from
internal sources (AtoZ) and external (supplier
database) are managed, to create a large and
high speed index. The resulting collection is vast
in size and in scope, but local indexing allows
exceptionally fast response times.
Features:
• Depth of indexing provides high-quality
metadata for the most viewed resources.
• Revelancy-ranked results speed users to the
information.
• Searchable full text available.
• Rich Metadata (Author Abstracts, Author
Keywords, Subject Headings, Full Text of
Articles, etc.)
• Widgets for SciFinder, Reaxys, NIST, ICSD,
Social Network, and more.
• Customization of the specialized databases
in activity area of Biqfr to avoid noise.
Main Databases
arXiv
Oxford
BioOne Online Journals
Publisher Provided Full Text Searching File
Center for Research Libraries
Research Starters
Directory of Open Access Journals
SciELO
eArticle
Science Citation Index
EDS Publication Finder
ScienceDirect
J-STAGE
Scopus®
MEDLINE
Supplemental Index
At the end of 2013, the Biqfr project “iLumina”
was launched as a single entry point to access
to scientific information. Observing the results
of the statistics, we find that many searches
have been made with few queries, in addition,
YearsSessions
the returned results were analyzed carefully
by consulting the abstracts, and then the most
relevant and applicable search results were
downloaded.
Searches
Abstracts Downloads
2013
816
24304
367
249
2014
2570
42951
2035
820
164
iLumina
It is available from the CSIC’s site to the whole
Institution, and ubiquitously through the VPN
to Biqfr users. Technology for mobile devices is
offered.
AtoZ
The resources AtoZ holds 30,654 journals &
books. The
Biqfr current subscriptions are
available online.
Simultaneously, This tool (AtoZ) has been an
access point to library’s electronic resources.
In 2013, the access for e-journals and for eBooks
was brought together into a single interface,
when the users were used to the application.
27,612 sessions were been made in 2013 and
15,812 in 2014. Whereas 15,747 researches
have been achieved in 2013, with a decrease
10,798 in 2014.
Upon launching iLumina, at the end of 2013,
a decline is seen in activity, which strongly
suggests that users prefer iLumina as a
knowledge manager, while they still use AtoZ for
a particular citation.
165
Document supply: Inter librarian
loan (ILL)
The wealth of the Biqfr’s holdings satisfies the
needs of its direct users, which is verified by
the small number of documents requested
to other centers and the significant number
documents supplied to external centers such
as universities, laboratories, and other CSIC
centers. As expected from modern science, 98%
of document transactions were journal articles
and only 2% were book loans. Remarkably, the
Biqfr supplied 17% of all the shared journal
articles within the whole CSIC Library Network.
The ILL is the key indicator of a library’s quality.
The Biqfr has consolidated its position as the
main supplier center at the CSIC. Over the
last 14 years, the average Biqfr ratio of the
supplied documents to requested documents is
ten. That is to say, the Biqfr supplied 10 times
more documents than we requested from other
centers. In the last years, this value decreased
to 7, due to the insertion at the Institute of
research lines in the areas of “Life Sciences”
whose resources are not directly available
to our library. In contrast, on the whole, the
CSIC Library Network is slightly deficitory as it
requests 1.03 documents for every document
that it shares.
Over the last years, the flow of internal
transactions among CSIC libraries has dropped
35% compared to 2001-2003, due to the
advance of new technologies and the collective
contracting by CSIC of the large packages of
electronic resources, provided by the main
publishers and other Institutions.
Nevertheless the number of documents supplied
to other institutions, has slowly decreased with
sight fluctuations. The level of total transactions
increased by 2.1 % between 2009 and 2010. On
the other hand, it decreased in 2011 by 5.8%,
to then experience an increase of 6.3% in 2012.
This level is similar to that of 2007. However, in
2013 the number of documents loaned dropped
by 6.3% and in 2014, it fell a further 12.8%.
In 2014, we should remark that there was a
21% decline in the number of Biqfr supplied
documents to the CSIC centers, which could be
reasonably explained by a putative decrease of
the CSIC’s scientific activity and the closing of
libraries at some CSIC centers.
166
During 2013, the total number of document
transactions was 3,978 (both supplied and
requested.) Of these, 3,505 documents were
delivered (-0.3 % lower than 2012) with 1,800
being sent to the CSIC’s library Network (-2.1%
lower than 2012) and 1,705 to other institutions
(1.6% higher than 2012). Regarding our
requests, 473 documents (14.1% lower than
2012); were obtained from other libraries, of
which 219 (7.1% lower than 2012) came from
CSIC’s network and 254 documents (11.8 lower
than 2012) were sent by other institutions. 19.7
% documents requested from other libraries
were supplied by Subito. Of these 3,505
167
documents supplied, 3,366 came from journal
articles and 31 were book loans.
During 2014 total number of items loaned or
borrowed was 3,505, of which 3,055 documents
were delivered (12.8 % lower than 2013) with
1,420 being supplied to CSIC’s library Network
(21.1% lower than 2013) and 1,635 to other
institutions (4.1% lower than 2013). On the
other hand, 450 documents (4.8% lower than
2013) were requested from other libraries, of
which 251 (14.6% higher than 2013) came from
CSIC’s network and 199 (21.6 % higher than
2013) were sent by other institutions, with 25.6
% of these documents coming from Subito. Of
these 3,055 documents supplied, 3,024 came
from journal articles, while 31 were book loans.
The number of book loaned to users was 35 in
2013 and 38 in 2012. The number of book loaned
showed a marked decrease of 53% compared
with 2012.
Economic implications
During the last two years of economic crisis,
the human and financial resources of the Biqfr,
like the rest of the CSIC, have been severely
damaged:
Our staff has been reduced by one third with one
technician retiring and a second on extended
leave. The remainder of the staff has been
forced to fill gaps while maintaining its activity.
In many cases this has been a difficult and
arduous task, surpassed only by the goodwill
and enthusiasm its members. The situation is
further aggravated if you consider that staff is
aging and further retirements are planned. This
situation cannot be extended for much more
time without risking a possible closing of the
library.
In 2010, Biqfr had a book acquisition budget
of 46.430 €. Afterwards, a centralized office,
the URICI (Unit of Information Resources for
Research) was placed in charge of the acquisition
of books for the libraries of the network, and
Biqfr has been uninvolved in the selection of
books. Furthermore, since 2012 no funds have
been allocated acquire new books or journal
subscriptions. So, unfortunately, since 2013 no
new books related to the IQFR’s activity have
been incorporated.
Furthermore,
most journals are no longer
subscribed to in paper, but only in the electronic
format. Hence many are unavailable in the print
edition, as is the case for the International Journal
of Chemical Kinetics, Chemistry Letters, Russian
Chemical Reviews (devoted to reviews, this is
the English version of the legendary Uspekhi
Khimii, the flagship of Russian Chemistry) etc.
In 2013, due to economic cuts, many electronic
resources were not subscribed to by the CSIC
Library Network. In 2014 some subscriptions
were renovated but all. This change represents
an impoverishment of our cultural heritage,
because some publishers (IOP, Wiley, Springer,
etc.) cut electronic access when the subscription
is dropped, even to the years that the journals
were purchased in paper.
Currently only 44 journals are subscribed to in
print, compared with 169 journals in 2012.
Standard management
The Biqfr has continued the work of technical
process, collections control, organization of the
holding and signaling, maintaining the reading
room service, etc.
Collection improvement
In 2013, a project aimed to improve the collection
by reviewing the holdings located in various
IQFR offices or departments was executed.
This required locating each of the 1193 items in
different departments, checking to ensure that
the location in the network collective catalog
was correct, error correction if necessary, and
finally, cataloging and classification of issues not
included in the catalog.
168
Administration-Stockroom-Reception
Management and Administration
Stockroom
Manager
Consuelo Martín de Loeches
(Stockroom Manager)
Isabel Cabo Chaves (until 14/02/2014)
Antonio Rubinos Pérez (from 15/02/2014)
Administration
Julia Cano García (Paymaster)
Sagrario Salado Rey
José Enrique García Ortega
Elvira Calviño López (until 01/11/2013)
Gloria Alonso Gómez
Pilar Ruiz Lafita
Mª Mar de la Torre Tante
Gloria Pinillos Pérez (from 01/11/2014)
Eva María Carpintero Vázquez
Reception
Mercedes Sanz Martín (until 01/08/2014)
Ángela Manso Asensio (until 11/02/2013)
José Luis Rodríguez Garro
(from 12/02/2013)
Technical Support Units
Electronics Workshop
Computer Support
Pedro Durán Martín (Head)
Antonio Díaz Pozuelo
Miguel Rodríguez Artigas
David Armenteros Escabias
Pedro J. Navarrete Bodorrey
Building Maintenance
Mechanics Workshop
Jesús López Mascaraque (Head)
José Antonio Serna Ferrero
José Antonio Mulero Bravo
Ignacio Sanz Gómez
Juan Luis Martínez García
Glassblowing Workshop
Nicomedes San Román Prieto
Singular Instrumentation
Laboratory for single
diffraction (DRXM)
crystal
X-ray
The services offered by the laboratory are
aimed at obtaining: a) single crystals, b)
X-ray diffraction patterns of single crystals
from samples of any nature: inorganic,
organic, organometallic, macromolecular
(proteins, enzymes) and polymer fibers,
and c) if required, the three dimensional
structure of the sample.
http://www.xtal.iqfr.csic.es/DRXM/
Scientific Manager: Armando Albert and
Martín Martinez-Ripoll
CSIC High-Field NMR Laboratory
small molecules and natural products.
The High Field NMR Laboratory has
cutting edge instrumentation and proven
experience of over 40 years in the analysis
of biomolecular structure and dynamics.
We also offer technical support with unique
experiments developed in our group, many
designed to study intrinsically unstructured
proteins (IDPs). The laboratory also provides
scientific advice for studying nucleic acids,
http://rmn.iqfr.csic.es/
Chromatography
and
Mass
Spectrometry
Laboratory
for
the
determination of molecular masses by
MALDI-TOF of molecules with masses
ranging from 1,000 to 300,000 u, especially
intact proteins.
Laboratory Director: Prof. Marta Bruix
Technical Manager: Dr. David Pantoja
Scientific
Committee: Prof. Jorge Santoro
Dra . Mª Angeles Jimenez
http://serviciomasas.iqfr.csic.es/
Scientific Manager: Rosa Lebrón Aguilar
Memoria 2013/2014
Memoria
Department
2013/2014of Instrumentación
Low Dimensional Systems,
174
Surfaces
174 and Condensed
Singular
Matter
Crystallyztion robots
crystallization experiments per plate.
Liquid handler for crystallyzation purposes,
Glison and Innovadine, for scaling from
militers to nanoliters. Setup for 96 or 192
(Responsibles: Armando Albert and Martín
Martinez-Ripoll)
X-ray diffractometer #1
Rotating anode X-ray source (2,7 kW,
MicroStar, Bruker), 100 μ micro-focus,
brilliance 3 times higher than conventional
rotating anodes. CuK α radiation through
Helios mirrors (Bruker).
Four-circle Kappa goniometer and CCD
detector (Bruker).
Cryoprotecting
system
(Oxford
Cryosystems) with N2 stream in the range
350-100 K.
Martinez-Ripoll)
This equipment shares the X-ray source
with diffractometer #1
Imaging plate Mar345dtb (MarResearch).
Cryoprotecting
system
(Oxford
350-100 K.
Martinez-Ripoll)
Scientific Report 2013/2014 Singular
175
Instrumentation
X-ray micro-source IμS (Bruker) for CuKα
X-ray radiation. Multilayer optics Elm3
(Bruker).
Four-circle goniometer with APEX II detector
(Bruker).
Cryoprotecting
system
(Oxford
350-100 K.
Martinez-Ripoll)
Gas chromatograph coupled to a quadrupolar
mass spectrometer, fitted with sample
introduction systems for liquids and gases
(Responsible: Rosa Becerra Arias).
Gas chromatographs for capillary and packed
columns, with flame ionization detectors
(Responsible: Rosa Lebrón Aguilar).
Diffferential Optical Absorption Spectroscopy (DOAS)/on-ground, ship, airborne and satellite
based instrument.
(Responsible: Alfonso Saíz López)
176
Instrumentation
Resonance and off resonance fluorescence
by lamp excitation (ROFLEX)/on-ground,
airborne.
(Responsible: Alfonso Saíz López)
Incoherent Broadband Cavity Enhanced
Absorption Spectroscopy (IBBCEAS).
Chemiluminiscence NOx.
(Responsible: Alfonso Saiz López).
Bruker AV-600 spectrometer
Cryoprobe TXI (1H,13C,15N)/Z gradients
Probe TXI (1H,13C,15N)/5 mm
Probe TBI (1H,13C, BB)/5 mm/gradients
Probe TXI (1H,13C,15N)/8 mm/Z gradients
Probe (1H-BB reverse)/10 mm
(Responsibles: D. Pantoja, M. Bruix)
Bruker AV-800 US2 spectrometer
Cryoprobe TCI (1H,13C,15N)/Z gradients
Probe TXI (1H,13C,15N)/5mm/ Z gradients
Probe QXI (1H,
gradients
C,
13
N, 31P)/5mm/ Z
15
(Responsibles: D. Pantoja, M. Bruix)
177
Instrumentation
Linear Triple Quadrupole TQ-high resolution FT-ICR Mass Spectrometer
FT-ICR (Fourier Transform Ion Cyclotron Resonance Spectrometry) a mass spectrometry
based on the effect produced by an intense magnetic field (generated by superconducting
solenoids) over the trajectories of charged particles (cyclotronic motion). As regards other
spectrometries, FT-ICR presents the best sensitivity and resolution currently available.
Our spectromter is a hybrid tandem MS of a Triple quadrupole (TQ) Agilent/Varian 320 in line
with high resolution FT-ICR Agilent/Varian-920 spectrometer, which is provided with a 7.0 T
actively shielded superconducting magnet.
• TQ is equipped with an electrospray ionization (ESI) source. It also has a nano-ESI source.
Its 2nd quadrupole is a CID chamber. TQ can be coupled to chromatographic interfaces
(either gas GC or liquid HPLC). The mass range of this spectrometer is between 20 and
2 000 m/z unids.
• Resolution of FT-ICR is in order of ppm. In MS terms it can be better than 106. This
spectrometer includes a MALDI (matrix-assisted laser desorption ionization) module,
whose range is between 50 and 10 000 m/z unids. In FT-ICR is possible to isolate ions
and perform a separated analysis of each of them. It is also possible to kinetically excite
(by radio frequencies, SORI-CID), selectively activate some of their bonds by IR radiation
(IRMPD) or non-selectively activate by electron capture (ECD).
• These options, lead to the fragmentation or controlled sequenciation of ions and provides
valuable information about the structure. The resulting technique allows not only to
perform identification and structural analysis of wide variety of species (from small to
macromolecular fragments) but being a powerful tool for following reactivity, energetics
and molecular interactions in the gas phase.
(Responsible: Juan Z. Dávalos Prado)
178
Instrumentation
Fluorescence multi-photon microscope and
confocal laser scanning (Olympus IX-71 /
Micro-Time 200-PicoQuant).
Excitation: Laser Ti-Za (2-photons; 750850 nm, 80 MHz, 100 fs) diodes (405 nm,
482 nm; 2.5-40 MHz; 100 ps). Detection
of fluorescence polarization, time-resolved
ps-s (TTTR-TCSPC). Temperature Control
(Responsible: M. Pilar Lillo)
Microarray platform
(Responsibles: Dolores Solís/María Asunción
Campanero-Rhodes)
Mössbauer Spectroscopy
(Responsibles: J.F. Marco and J. de la
Figuera)
Matrix assisted laser desorption/ionizationtime of flight mass spectrometer
(Responsible: Rosa Lebrón Aguilar)
179
Instrumentation
IQFR Facts and Figures
Formación Académica:
• PhD awardees
182
• PhD fellowship/contract holders
184
• Post-doctoral fellowship/contract holders
186
• Scientist exchange
187
• Courses and scientific meeting organization
192
• IQFR seminars cycles
194
Technology Transfer and Socio-Economic Impact:
• Patents
196
• Awards and distinctions 196
• Editorial and scientific committees
196
• Media coverage
199
Scientific Cloister
201
Board of Institute
203
Gender distribution of scientific staff
according to professional category
204
Summary of economic data
205
Scientific Report 2013/2014 Facts and
181
Figures
Academic Training
PhD awardees
Name
Department
Date
University
Thesis title
José Ignacio Crystallography and
23/09/2013
Universidad
Biología Estructural de
Baños Sanz
Structural Biology
Complutense Inositol Kinasas,
de Madrid
enzimas implicadas
en la regulación de inositol fosfatos
Cecilia Artola Crystallography and
07/04/2014
Universidad
Recolons
Structural Biology
Complutense
de Madrid
Biología Estructural de
Máquinas Moleculares
de Reciclaje de
Peptidoglicano.
Implicaciones en
Mecanismos de
Resistencias a
Antibióticos
Iván Acebrón
Crystallography and
01/07/2014
Universidad
Ávalos
Structural Biology
Complutense
de Madrid
Búsqueda racional de
nuevas etiquetas de
fusión: aplicaciones
biotecnológicas de los
dominios lectina trébol
beta
Antonio
Crystallography and
15/10/2014
Universidad
Chaves Sanjuan
Structural Biology
Internacional
Menéndez
Pelayo
Bases estructurales de
la homeostasis del
potasio en plantas:
Regulación del
transportador AKT1 y
de la quinasa CIPK23
Juan Manuel
Biological Physical
31/05/2013
Universidad
Ortiz Guerrero
Chemistry
de Murcia
Papel de la vitamina
B12 en la actividad de
una familia de factores
transcripcionales con
una novedosa
arquitectura de
dominios
Fernando Díez
Biological Physical
22/02/2013
Universidad Análisis conformacional
García
Chemistry
Complutense de péptidos prebioticos
de Madrid
plausibles y su
interacción con ácidos
nucleicos, arenos y
nucleótidos
Soraya Serrano
Biological Physical
04/06/2014
Universidad
Serrano
Chemistry
Complutense
de Madrid
182
Figures
Interacciones
proteína-membrana:
una aproximación
estructural por RMN
utilizando sistemas
modelo
Name
Department
Date
University
Thesis title
Santiago
Biological Physical
19/11/2013
Universidad
Martínez
Chemistry
Autónoma
Lumbreras
de Madrid
The role of Gbp2p,
Nab2p and Pub1p along
the mRNA cycle:
structural studies by
NMR and other
biophysical techniques
Silvia Lisa
Biological Physical
04/09/2013
Universidad
Ferrer
Chemistry
Complutense
de Madrid
Interruptores
moleculares en la
génesis de PrP
patógenas:
Metionilsulfósxidos y sus
modelos
Sebastián
Biological Physical
08/10/2013
Universidad
Raja
Chemistry
Autónoma
de Madrid
Conformational
Dynamics and Assembly
of the Ribosomal Stalk
Proteins
Nerea Martín
Biological Physical 06/2013
Universidad
Pintado
Chemistry
Autónoma
de Madrid
María Encina
Low Dimensional 01/07/2013
Universidad
López Arias
Systems, Surfaces
Complutense
and Condensed
de Madrid
Matter
Study of the Structure
and Stability of Nucleic
Acids with Modified
Furanoses Using NMR
Aplicaciones de plumas
de ablación de
semiconductores en
óptica no lineal y
síntesis de nuevos
materiales
Grégory
Low Dimensional
07/03/2013
Universidad
Gitzinger
Systems, Surfaces
Complutense
and Condensed
de Madrid
Matter
Dinámica de
predisociación y control
de la fotoionización de
yoduro de metilo con
pulsos láser de
femtosegundos
Luis Cerdán
Universidad
Systems, Surfaces
Complutense
and Condensed
de Madrid
Matter
Láseres de colorante
en estado sólido:
retroalimentación
por dispersión y
dispositivos integrados
Mª Eugenia
Low Dimensional
10/07/2014
Universidad
Pérez-Ojeda
Systems, Surfaces
Complutense
and Condensed
de Madrid
Matter
Matteo Monti
Systems, Surfaces and Condensed Matter
Universidad
Autónoma
de Madrid
183
Figures
Preparación y
aplicaciones ópticas
de sistemas híbridos
orgánicos-inorgánicos
basados en
silsesquioxanos
oligoméricos poliédricos
(POSS) funcionalizados con colorantes fluorescentes
Ultrathin iron oxide
films on Ru (0001)
PhD fellowship/contract holders
Department of Crystallography and Structural Biology
Name Funding body Starting date
Javier Gutiérrez Fernández
CSIC
2011-2014
Cecilia Artola Recolons
MINECO
2010-2014
Noelia Bernardo García
MINECO
2010
Teresa Domínguez Gil-Velasco
MINECO
2012
Alejandra Carriles Linares
CAM
2014
Elsa Franco Echevarría
MINECO
2012
María Ángela Polo Sainz
CSIC
2013
Mercedes Ramírez Escudero
MINECO
2012
Iván Acebrón Ávalos
MINECO
2011-2014
Yanaisis Álvarez Sánchez
CSIC-CITMA
2010-2014
Antonio Chaves Sanjuan
MINECO
2010-2014
Supervisor
Juan A. Hermoso
Juan A. Hermoso
Juan A. Hermoso
Juan A. Hermoso
Juan A. Hermoso
José Miguel Mancheño
José Miguel Mancheño
Martín Martinez Ripoll
Ernesto Moreno
Armando Albert
Department of Structure, Energy and Chemical Reactivity
Name
Francisco Javier González
Funding body
Starting date
Supervisor
FPI, MINECO
01/09/2010
JZ Dávalos Prado
Department of Biological Physical Chemistry
Name
Funding body
Soraya Serrano Serrano
FPI, MINECO
Héctor Zamora Carreras
FPI, MINECO
Juan Manuel Ortiz Guerrero
JAE-pre, CSIC
Santiago Martínez Lumbreras
CAM
Angélica Inés Partida Hanón
Proyecto
Jesús Fernández Zapata
FPI, MINECO
Aránzazu Gallego García
Proyecto
Javier Martínez Fernández
MINECO
Erney Ramírez
JAE-Pre (CSIC)
Palma Rico Lastres
FPI, MINECO
Lara López Merino
JAE-Pre (CSIC)
Starting date
Supervisor
01/11/2009
01/12/2012
01/09/2008
01/01/2009
01/09/2014
01/01/2014
01/10/2014
01/09/2010
01/05/2010
21/06/2010
01/11/2009
M. Bruix, M.A. Jiménez
S. Padmanabhan
J.M. Pérez-Cañadillas
S. Padmanabhan
S. Padmanabhan
M. Gasset
P. Chacón
M. Menéndez
Mª D. Solís
184
Figures
Name
Funding body
Starting date
Guadalupe García
CIBERES
15/06/2012
Moreno
Ioanna Kalograiaki
FP7-ITN- GA:289003
01/08/2012
Radoslaw Borowski
FP7-ITN-GA:317297
01/09/2013
Miguel Mompean García
FPI
11/2012
Nerea Martín Pintado
JAE
06/2009
Miguel Garavís
FPI (CBMSO)
10/2009
Supervisor
M. Menéndez
Mª D. Solís
Mª D. Solís
D.V. Laurents/
C. González
C. González
C. González
A. Villasante
Department of Low Dimensional Systems, Surfaces and Condensed Matter
Name
Funding body
Starting date
Ignacio López Quintás
FPI, MINECO
01/09/2011
Luis Cerdán
Research Project
01/10/2012-
28/02/2013
Supervisor
Marta Castillejo
Striano y Margarita
Martín Muñoz
Angel Costela e
Inmaculada
García-Moreno
Mª Eugenia Pérez-Ojeda
JAE-Pre (CSIC)
01/09/2009
Inmaculada García-Moreno y
José Luis Chiara
Gonzalo Durán
FPI, MINECO
01/08/2011
Inmaculada García-Moreno y
Mª José Ortiz
FPI, MINECO
01/12/2011
Vicente Sánchez Gil
CSIC
01/10/2011
Matteo Monti
FPI, MINECO
01/09/2010-
01/09/2014
Laura Martín
FPI, MINECO
01/01/2014
185
Figures
Enrique Lomba
García
Eva González
Noya
Juan de la Figuera
y J.F. Marco Juan de la
Figuera y J.F. Marco
Post-doctoral fellowship/contract holders
Department of Crystallography and Structural Biology
Name
Funding body
Starting date
Lisandro Otero
NIH
2011-2013
César Carrasco López
CSIC
2013
Iván Acebrón Ávalos
CSIC
2013
Sergio Galán Bartual
MINECO
2012-2014
MINECO
01/10/2014
Supervisor
Juan A. Hermoso
Juan A. Hermoso
Juan A. Hermoso
Juan A. Hermoso
María José
Sánchez Barrena
Department of Structure, Energy and Chemical Reactivity
Name
Carlos Alberto Cuevas Rodríguez
Rafael Pedro Fernández Cullen
Cristina Prados Román
Funding body
Starting date
MINECO
MINECO
MINECO
03/2013
03/2013
03/2013
Supervisor
Alfonso Saiz López
Alfonso Saiz López
Alfonso Saiz López
Department of Biological, Physical Chemistry
Name
M. Flor García Mayoral
José Ramón López-Blanco
Mónica Álvarez Pérez
Funding body
Starting date
Supervisor
Project
M. Bruix
CAM/MI
P. Chacón
EU-FP7
(GlycoHIT project)
01/06/2012
Mª D. Solís
CSIC
CIBERES
12/05/2014
30/11/2009
M. Menéndez
Mª Asunción Campanero Rhodes
JAEDoc (CSIC)
16/09/2011
Mª D. Solís
CAM (BIPPED-2)
CSIC
CIBERES
15/07/2012
13/02/2014
10/09/2014
M. Menéndez
JAE
01/01/11
C. González
Manuel Iglesias Bexiga
Irene Gómez Pinto
186
Figures
Department of Low Dimensional Systems, Surfaces and Condensed Matter
Name
Funding body
Starting date
Luis Cerdán
Research Project
01/03/2013
Raquel Gargallo
Research Project
01/03/2014
Supervisor
Angel Costela e Inmaculada
García-Moreno
Juan de la Figuera
Scientist exchange
Name
Home
institution
Teresa IQFR/CSIC
Domínguez Gil-Velasco
DestinationDates Department
institution
Univ. de Notre
28/04/14-
Dame (USA)
25/07/14
Crystallography
and Structural
Biology
Renee Bouley
Univ. de Notre Dame IQFR/CSIC
26/05/14-
(USA)
01/07/14
Crystallography
and Structural
Biology
Ángel Vizoso
Univ. de La Coruña
IQFR/CSIC
O1/10/2013-
31/12/2013
Crystallography
and Structural
Biology
Lourdes Infantes
IQFR/CSIC
CCDC 01/10/2013-
Cambridge, UK
30/09/2014
Crystallography
and Structural
Biology
Laura Salum
CIHIDECAR- QFR/CSIC
16/12/2013-
CONICET, 14/03/2014
Argentina
Structure,
Energy and
Chemical
Reactivity
Violeta Romero
Universidad
IQFR/CSIC
01/12/2014-
Federico 31/12/2014
Villarreal,
Lima-Perú
Structure,
Energy and
Chemical
Reactivity
Arminda
Tirado
Universidad
IQFR/CSIC
01/12/2014-
Federico
31/12/2014
Villarreal,
Lima-Perú
Structure,
Energy and
Chemical
Reactivity
Anoop
Indian Institute
IQFR/CSIC
04/2014
of Tropical
Mahajan
meteorology
Structure,
Energy and
Chemical
Reactivity
Juan Carlos
University of Leeds
IQFR/CSIC
04/2014
Gómez Martín
Structure, Energy and
Chemical
Reactivity
187
Figures
Name
Home
institution
Destination
institution
DatesDepartment
Chistopher University of New-York
IQFR/CSIC
04/2014
Blaszczack-
Boxe
Structure,
Energy and
Chemical
Reactivity
Rafael Pedro CONICET
IQFR/CSIC
05/2014
Fernández Cullen
Structure,
Energy and
Chemical
Reactivity
María Navarro
University of Miami
IQFR/CSIC
08/09/2014
Structure,
Energy and Chemical
Reactivity
Héctor Zamora
IQFR/CSIC
IBG-KIT center
01/08/2014-
20/11/2014
Biological Physical
Chemistry
D. Soler
U. Girona
IQFR/CSIC
14/01/2013-
13/05/2013
Biological Physical
Chemistry
Carlos A. U. Nova de Lisboa
IQFR/CSIC
Salgueiro
11-18/02/2013 Biological Physical
01-14/07/2013
Chemistry
11–19/02/2014
Joana Dantas
U. Nova de Lisboa
IQFR/CSIC
11–18/02/2013 Biological Physical
01–14/07/2013
Chemistry
Palma Rico IQFR/CSIC
Lastres
Ioanna
IQFR/CSIC
Kalograiaki
University of
Newcastle
02/09/2013
30/11/2013
Semelweis University
26/03/2013
Faculty of Health
and Public
Services
(Budapest)
Biological Physical
Chemistry
Biological Physical
Chemistry
Ioanna
IQFR/CSIC
Kalograiaki
Instituto de
Agro-
biotecnología
CSIC-UPNA
(Pamplona)
06/10/2013
10/11/2013
Biological Physical
Chemistry
Ioanna IQFR/CSIC
Kalograiaki
Royal Institute
of Technology
(KHT)
08/09/2014
26/09/2014
Biological Physical
Chemistry
28/09/2014
10/10/2014
Biological Physical
Chemistry
06/10/2014
05/12/2014
Biological Physical
Chemistry
University of
IQFR/CSIC
01-04/2014
Texas,
San Antonio/ EEUU
Biological Physical
Chemistry
Ioanna Kalograiaki
Radoslaw IQFR/CSIC
CIB/CSIC
Borowski
Paul Fitzpatrick
IQFR/CSIC
ATTANA AB
(Estocolmo)
188
Figures
Name
Santiago Ruiz Martínez
Patrick J.B. Edwards
Hala Abou Assi
Home
institution
institution
University of
IQFR/CSIC
09-11/2014
Gerona
Massey University,
IQFR/CSIC
04/2013
Palmerston North,
Nueva Zelanda
Mcgill University,
IQFR/CSIC
09-11/2014
Montreal/
Canada
Alfredo
CBMSO/CSIC
IQFR/CSIC
Villasante
Daniele Cioffini
01/01/2013
31/12/2014
Istituto di
IQFR/CSIC
27/01/2014- Fisica Applicata 30/07/2014
“Nello Carrara”
Consiglio Nazionale delle Ricerche,
Sesto Fiorentino, Italia
Marta IQFR/ CSIC
Castillejo Striano
Blackett
09/2012-
Laboratory,
02/2013
Imperial College
London,
Reino Unido
Biological Physical
Chemistry
Biological Physical
Chemistry
Biological Physical
Chemistry
Biological Physical
Chemistry
Low Dimensional
Systems,
Surfaces and
Condensed
Matter
Low Dimensional
Systems,
Surfaces and
Condensed
Matter
Mª Eugenia IQFR/CSIC
Lund University,
01/05/2013-
Pérez-Ojeda
Lund, Suecia
01/07/2013
Low Dimensional
Systems,
Surfaces and
Condensed
Matter
Vicente IQFR/CSIC
Universidad 08/10/2013
Sánchez Gil
Federal
08/11/2013
Rio Grande
do Sul (Brasil)
Low Dimensional
Systems,
Surfaces and
Condensed
Matter
Vicente IQFR/CSIC
Institute of Solid
01/09/2014
Sánchez Gil
State Physics,
01/11/2014
Budapest
Low Dimensional
Systems,
Surfaces and
Condensed
Matter
Cecilia IQFR/CSIC
Universidad
23/05/2014
Bores Quijano
Federal
23/06/2014
Rio Grande do Sul (Brasil)
Low Dimensional
Systems,
Surfaces and
Condensed
Matter
Low Dimensional
Systems,
Surfaces and
Condensed
Matter
Cecilia Bores IQFR/CSIC
Technische
01/04/2013
Quijano
Universität Wien
21/12/2013
189
Figures
Name
Home
institution
institution
Cecilia Bores IQFR/CSIC
Department of
03/09/2014
Quijano
Chemical
03/12/2014
Engineering, University of Edinbourgh
Jakub Pekalski
Institute of
IQFR/CSIC
04/05/2013
Physical
28/06/2013
Chemistry
(Polish Academy
of Sciences)
Varsovia
Alexandre Universidad
IQFR/CSIC
12/03/2014
Furlan
Federal Rio
10/04/2014
Grande do Sul (Brasil)
Enrique IQFR/CSIC
Universidad
17/09/2013
Lomba García
Federal Rio
01/10/2013
Grande do Sul
(Brasil)
Low Dimensional
Systems,
Surfaces and
Condensed
Matter
Enrique IQFR/CSIC
Université Pierre
01/10/2014
Lomba García
et Marie Curie
02/11/2014
Jussieu (Paris)
Low Dimensional
Systems,
Surfaces and
Condensed
Matter
Noe García IQFR/CSIC
Universidad
20/04/2014
Almarza
Federal Rio
02/05/2014
Grande do
Sul (Brasil)
Eva González IQFR/CSIC
Universidad
15/07/2013
Noya
Federal
27/07/2013
Rio Grande
do Sul (Brasil)
Low Dimensional
Systems,
Surfaces and
Condensed
Matter
Low Dimensional
Systems,,
Surfaces and
Condensed
Matter
Eva González
IQFR/CSIC
Technische
24/09/2014
Noya
Universität
02/10/2014
Wien (Austria)
Low Dimensional
Systems,
Surfaces and
Condensed
Matter
Matteo IQFR/CSIC
Berkeley National 15/08/2013
Monti
Labs (EEUU)
26/10/2013
Low Dimensional
Systems,
Surfaces and
Condensed
Matter
190
Figures
Low Dimensional
Systems,
Surfaces and
Condensed
Matter
Low Dimensional
Systems,
Surfaces and
Condensed
Matter
Low Dimensional
Systems,
Surfaces and
Condensed
Matter
Name
Home
institution
institution
Juan de la IQFR/CSIC
Figuera
Labs (EEUU)
16/08/2013
Low Dimensional
Systems,
Surfaces and
Condensed
Matter
José F. Marco
IQFR/CSIC
Universidad de
22/06/2013
Chile (Santiago,
14/07/2013
Chile)
Low Dimensional
Systems,
Surfaces and
Condensed
Matter
Laura Martín IQFR/CSIC
García
Labs (EEUU)
09/09/2014
Low Dimensional
Systems,
Surfaces and
Condensed
Matter
Juan de IQFR/CSIC
la Figuera
Labs (EEUU)
02/09/2014
Low Dimensional
Systems,
Surfaces and
Condensed
Matter
José F. Marco
IQFR/CSIC
Universidad de
06/11/2014
Santiago de
27/11/2014
Chile (Chile)
Low Dimensional
Systems,
Surfaces and
Condensed
Matter
191
Figures
Courses and scientific meeting organization
Organizer
Class
Title
Date
Place
Juan A. Scientific Congress
Hermoso
XIV Congress 11-13/06/2014
of The Spanish Biophysical
Society
Juan A. Scientific Congress
Hermoso
11th European
Meeting on
the Molecular
Biology of the
Pneumococcus
28-31/05/2013
Madrid
Juan A. Workshop
Hermoso
Armando Albert
Macromolecular
Crystallography
School
6-10/05/2013
Madrid
Juan A. Workshop
Hermoso
Armando Albert
Macromolecular
Crystallography
School
26-31/05/2014
Madrid
José Miguel Course
Mancheño
Rosa Lebrón Specialization
Aguilar
course
Aguilar
course
Protein
11-12/04/2013
Crystallography Course
Alcalá de
Henares
TARTU
(Estonia)
Cromatografía
de Líquidos
acoplada a la
Espectrometría
de Masas
25-28/11/2013
IQFR/CSIC
Cromatografía
de Líquidos
acoplada a la
Espectrometría
de Masas:
1ª edición 2014
13-16/10/2014
IQFR/CSIC
Cromatografía
27-30/10/2014
Aguilar
course
de Líquidos
acoplada a la
Espectrometría
de Masas:
2ª edición 2014
Marta Bruix
Organizer Congreso GERMN
22-25/09/2014
Committee
IQFR/CSIC
Marta Bruix
Organizer
Congreso SBE
11-13/06/2014
Committee
192
Figures
Alcalá de
Henares
Alcalá de
Henares
Organizer
Class
Title
DatePlace
Dolores Solís
Workshop
DYNANO-
30/09/2013
GLYCOPHARM
02/10/2013
Summer School
Dolores Solís
Course
Chemical Glycobiology 06/06/2013
& Biomedicine.
Principles of
the Sugar Code
Douglas.V. Symposium
Laurents
First Symposium of
20/02/2014
Young Researchers of
the “Rocasolano” Institute
of Physical Chemistry
Mohamed Oujja
Workshop within
Laser cleaning
11/2013 y
CSIC Science
11/2014
Week
Marta Castillejo Symposium
“Laser Materials
27-31/05/ Striano
Interactions for
2013
Micro and Nano
Applications”
E-MRS Spring
Meeting
Marta Castillejo User’s
4th LASERLAB-
26-27/09/
Striano
Meeting
Europe III
2013
User’s Meeting,
“Using laser sources
and secondary
sources as
diagnostic tools
for science
Esther Rebollar Workshop
González
Jornadas de
23-24/09/
microscopía AFM.
2014
Presentación de
la plataforma
AFM MultiMode
8 de Bruker
Nano Surfaces.
Estado del arte,
soluciones y
sesiones prácticas
de manejo del
microscopio
MultiMode 8
193
Figures
Centre of
Biological
Research
(CIB-CSIC)
UCD School
of Chemistry
and Chemical
Biology
University
College (Dublin)
IQFR/CSIC
IQFR/CSIC
Strasbourg,
France
Laboratoire
Lasers,
Plasmas et
Procédés
Photoniques
(LP3),
Marsella,
Francia
Instituto de
Estructura
de la Materia
CSIC, Madrid
Organizer
Class
Title
DatePlace
CSIC training Course: Scientific
Creation of 21/03/2013
office Culture and
digital Identity:
(Biqfr)
Communication
The Web 2.0.
CSIC-MadrI+D
Outreach: the Night
El Rockefeller
27/09/2013
(Biqfr)
of the Researchers
y el espíritu
The Rockefeller Rockefelleriano
Building and its Spirit
Biqfr
Workshops
Presentation of
iLumina
06/02/2014
Royal Botanical
Garden.
Madrid
IQFR/CSIC
IQFR/CSIC
IQFR seminars cycles
Speaker
TitleDate
Frequenin/NCS-1 as a pharmacological
target for synapse regulation in
X-linked mental retardation and autism
17/12/2014
María José Sánchez
Barrena
Lourdes Infantes
Bin2 is a membrane sculpting N-BAR
protein that influences leucocyte
podosomes, motility and phagocytosis
13/02/2013
Structural Information in Chemistry
18/11/2014
William Seitz
Alfonso Saiz López
Carlos Alberto
Cuevas Rodríguez
Entropy vs. Mixing: What
Determines Complexity
27/05/2014
Atmospheric Chemistry and climate group
04/06/2013
Evolution of NO2 levels in Spain from 1996
to 2012 and UVAS retrieval algorithms
12/03/2014
A negative feedback between
anthropogenic ozone pollution and
enhanced ocean emissions of iodine
23/04/2014
Lara López Merino
The galectins: so similar,
so different
27/06/2013
Palma Rico Lastres
Structural and functional characterization
of the LytB glucosaminidase
from Streptococcus pneumonia
26/03/2014
Study of substrate specificity of
CW_7 cell-wall binding-motifs
from the Cpl-7 endolysin
30/04/2014
Cristina Prados Román
194
Figures
Speaker
Ioanna Kalograiaki
TitleDate
Exploring glycosylation patterns
in pathogenic bacteria and
extracellular vesicles as markers
for endogenous receptors
11/06/2014
Rubén Martínez-Buey
Recognition mechanisms of +TIPS
proteins (TIP interacting proteins)
06/06/2014
Nerea Martín Pintado
Interacciones no convencionales
en ácidos nucleicos modificados
04/2013
Estructuras no canónicas en ácidos
nucleícos teloméricos y centroméricos
18/06/2014
Detener el tiempo: pulsos de luz
para observar cambios ultrarrápidos
08/05/2014
Laser controlled fabrication
of nanostructures
18/11/2014
Dinámica y transiciones de fase de
fluidos complejos adsorbidos en
vidrios porosos
09/04/2014
Miguel Garavís
195
Figures
Technology Transfer And Socio-Economic Impact
Patents
Authors
Title YearCode
Alfonso Saiz López, Arturo Alonso, Chiara Cerruti, Tomás Belenguer Dávila
Sonda atmosférica
para detección
remota a alta
resolución de
gases traza
2014
ES 201431130
Pedro García,
Margarita Menéndez,
Ernesto García,
Roberto Díez,
Héctor de Paz,
Noemí Bustamante
Improved bactericidal
enzybiotics against
the pneumococcus
and other bacteria
2013 (Spain)
2014 (International)
P201330777
PCT/ES2014/070429
Awards and distinctions
•
Marta Bruix: The RSEQ NMR Group (GERMN) Bruker Prize, September 2014.
•
Nerea Martín Pintado, Prize of the best PhD thesis award in the field of NMR, granted by RSEQ
NMR Group (GERMN)
•
Luis Cerdán was awarded the Innova Scientific Award 2013 (awarded by Innova Scientific) to
the best-published work on experimental photonics, and Premio Extraordinario de Tesis Doctoral.
Editorial and scientific committees
Participant
Committee/Journal
Role
Martín Martínez Ripoll, Comité editorial
Juan A. Hermoso and Colección Divulgación
Armando Albert
Eds. CSIC (2014)
ISBN: 978-84-00-09800-1
Eds. Catarata (2014)
ISBN: 978-84-8319-906-0
Armando Albert
Coordinators and
authors
Book “A través del
Cristal. Cómo la
cristalografía ha
cambiado la vision
del mundo”.
Grupo Especializado de
Cristalografía y
Crecimiento CristalinoRSEQ
Treasurer
196
Figures
Participant
Alfonso Saiz López
Alfonso Saiz López
Committee/Journal
Role
Mission Advisory Group of
the European Space Agency’s
Earth Observation Satellite
Sentinel-5 Precursor, TROPOMI
Mission and
scientific requirements
Scientific Steering Committee
Definition of
of the international
strategic goals:
Surface Ocean-Lower
atmospheric chemistry
Atmosphere Study (SOLAS)
Alfonso Saiz López
Scientific Report
Editorial Board Member
Alfonso Saiz López
Science, Nature, PNAS,
JGR, Geophysical Research
Letters, Atmos. Chem
Phys., Environmental
Chemistry, NASA, NSF,
NRC, DFG, NERC
Reviewer
Alfonso Saiz López
Tropospheric halogen
sesión at AGU
2014 and EGU 2013
and 2014 meetings
Coordinator
PLosOne
Editor
ISRN Biophysics
Editor
IUPAC Photochemistry Group
Project member
María A. Gasset
M. Pilar Lillo
A. Ulises Acuña
Douglas V. Laurents
Arch. Biochem. Biophys.
Editorial Board
Member
Elected Member as
Chair of the Board of User’s
Representatives and Member
of Management Committee
of LASERLAB Europe III
(Integrated Initiative of European
Laser Infrastructures
(7º EU Framework Program)
Monitoring of user access
to laser infrastructures
within LASERLAB Europe.
LASERLAB Europe,
Participation in the
management of the
Consortium. From 01/2009
International Conference LACONA
(Lasers in the Conservation
of Artworks)
Member of Permanent
Scientific Committee
From 11/2003
International Conference O3A,
Optics for Arts, Architecture
and Archaeology, SPIE
International Symposium on
Optical Metrology, Munich,
Germany. 06/2013
Member of Permanent
197
Figures
Participant
Committee/Journal
Role
International Conference
TECHNART 2013, Analytical Spectroscopy in Art and
Archaeology at the Rijksmuseum,
Amsterdam. 23-27/09/2013
Member of Permanent
International Symposium
“Light-Matter Interactions and
Materials” within the
Internacional Conference on
Lasers and Electrooptics, CLEO
2013 y CLEO 2014,
San Jose, California, USA
Member of Scientific
Committee of the
Symposium
Symposium “Light-Matter
Interactions and Materials” within the Internacional Conference on Lasers and Electrooptics CLEO
Europe 2013, Munich, Germany
Member of Scientific
Committee of the
Symposium
Condensed Matter Physics (Ukraine)
Member of the
Editorial Committee
José F. Marco
Applications of the Mössbauer Effect
Member of the
International Advisory
Board (05/2007-05/2013)
José F. Marco
International Symposium on the Industrial Applications of the Mössbauer Effect
Member of the Scientific
Executive Committee
José F. Marco
International Conference on the Applications of the Mössbauer Effect. 2013, Opatija, Croacia
Member of the
International
Programme Committee
José F. Marco
Mössbauer Effect Data Center
Member of the
International Advisory
Board (from 2007)
198
Figures
Media coverage
Name
Media and date
Juan A. Hermoso
CSIC (08/05/2014) http://bit.ly/1Ca2GB3
Juan A. Hermoso
RTVE (08/05/2014) http://bit.ly/1ECFPhE
Juan A. Hermoso
Terra (08/05/2014) http://bit.ly/1AhBJVC
Juan A. Hermoso
DOCSALUD.com (20/05/2014) http://bit.ly/1C8tqjH
Juan A. Hermoso
El Universal (09/05/2014) http://bit.ly/1FRLOwt
Juan A. Hermoso
IMPACTO.mx (08/05/2014) http://bit.ly/1B8mT32
Juan A. Hermoso
ABC salud (08/05/2014) http://bit.ly/1GIKkIv
Juan A. Hermoso
La Voz Digital (09/05/2014) http://bit.ly/1xgtLLt
Juan A. Hermoso
Entorno Inteligente (09/05/2014) http://bit.ly/1wyrkc6
Juan A. Hermoso
Vive Sana (09/05/2014) http://bit.ly/1GIKFuu
Juan A. Hermoso
Diario de Yucatán (08/05/2014) http://bit.ly/1F2TTzH
Juan A. Hermoso
El Diario Montañés (08/05/2014) http://bit.ly/1FRN7LH
Juan A. Hermoso
EFE-Futuro (08/05/2014) http://bit.ly/1wyrJLs
madri+d:(23/4/2013) http://bit.ly/1Ca45Yj
La Razón (25/4/2013) http://bit.ly/1D9WWqJ
CSIC (22/04/0143) http://bit.ly/1D9XkWj
SoloCiencia.com (22/04/2013) http://bit.ly/1b4xTd1
Química y Sociedad (23/04/2013) http://bit.ly/1GvIYNJ
Negocio Tecnológico (30/04/2013) http://bit.ly/1Ca4olT
Diario de Sevilla (29/04/2013) http://bit.ly/1Bvpx7K
paperblog – Empresa (01/05/2013) http://bit.ly/1AhDceM
Anales de Química (2013, 109(2): 161-166) http://bit.ly/18eBMu4
fisicahoy (23/04/2013) http://bit.ly/1wysK6l
199
Figures
Name
Media and date
Bitnavegantes (22/04/2013) http://bit.ly/1xgvpg1
Sinc (22/04/2013) http://bit.ly/1L1LQsb
Asaja (26/04/2013) http://bit.ly/1C8PM4K
Martín Martínez Ripoll
La ONU declara 2014 Año Internacional
de la Cristalografía. En Análisis Madri+d,
28 Enero 2014 http://bit.ly/1NScvXg
Clara Gómez
Ortodoncia Española (2014, 52(3): 7-15)
(Prize of the best article edited
in Ortodoncia Española, 2014)
Biqfr
Support document management for the
preparation of the book dedicated
to the 75th anniversary of CSIC. (2014)
Biqfr
Has been involved with several
holdings in the exhibition: The Generation
of 1914. Science and Modernity. Organized by
de National Library 14/03-01/06 (2014)
Biqfr
Has been involved with several holdings
in the exhibition: Marie Sklodowska
Curie: a Polish Woman in Paris. Organized by
Natural Sciences Museum. 05/03-15/10 (2014)
Biqfr
Has been involved with several holdings in
the exhibition: The internationalization of Spanish
Culture. Organized by the Students´Residence (from 24/11/2014)
200
Figures
Scientific Cloister
President:
(Until 03/07/2013)
(Professor)
Juan de la Figuera Bayón (From 04/07/2013)
Secretary:
Members: A. Ulises Acuña Fernández
(Professor Ad honorem)
Manuel Rico Sarompas
(† 01/12/2014)
Claudio Gutiérrez de la Fe
Marta Bruix Bayés
(Professor)
Ángel Costela González
(Professor)
Francisco Javier García de Abajo
(Until 31/05/2013)
(Professor)
Inmaculada García-Moreno Gonzalo
(Professor)
(Professor)
Juan A. Hermoso Domínguez
(Professor)
(Professor)
Martín Martínez Ripoll
(Professor)
(Professor)
Jorge Santoro Said (Professor)
Rosa Becerra Arias
Ángel Cuesta Ciscar
(Until 30/06/2013)
María A. Gasset Vega
Mª Ángeles Jiménez López
Margarita Martín Muñoz
Margarita Menéndez Fernández
Subramanian Padmanabhan
Alfonso Saiz-López
Juliana Sanz Aparicio (Associate Professor)
Ángel Vegas Molina
(Until 31/10/13)
201
Figures
Members:
Pablo Chacón Montes
Juan Z. Dávalos Prado
Pablo Echenique Robba (Assistant Professor)
Clara Gómez Hernández
Eva González Noya
Lourdes Infantes San Mateo
Douglas V. Laurents
Rosa Lebrón Aguilar
Mª Pilar Lillo Villalobos
José Miguel Mancheno Gómez
Claudio Martín Álvarez
(Until 24/10/2013)
José Mª Oliva Enrich
José Manuel Pérez Cañadillas
José Mª Santiuste Bermejo
Silvia Zorrilla López
(Until 15/06/2013)
Esther Rebollar González
(Ramón y Cajal Contract)
Mª José Sánchez Barrera
(Ramón y Cajal Contract)
202
Figures
Board of Institute
President: Enrique Lomba García
(Director until 03/07/2013)
(Director from 04/07/2013)
Secretary: Isabel Cabo Chaves
(Administrator until 14/02/2014)
Members:
(Vice director until 03/07/2013)
(Vice director until 03/07/2013)
Douglas V. Laurents
(Vice director from 04/07/2013)
Juan Dávalos Prados
(Vice director from 04/07/2013)
(Head of Department of Crystallography and Structural Biology)
(Head of Department of Structure, Energy and Chemical Reactivity)
Marta Bruix Bayés
(Head of the Department of Biological Physical Chemistry)
(Head of the Department of Low Dimensional Systems, Surfaces and
Condensed Matter).
(Personnel representative)
Mª Carmen Pérez Bécares
(Personnel representative until 12/06/2014)
Antonio Rubinos Pérez
(Personnel representative until 14/02/2014)
Jesús López Mascaraque
(Personnel representative)
Antonio Rubinos Pérez
(Administrator from 15/02/2014)
203
Figures
Gender distribution of scientific staff according to
professional category
Category
WomenMen
Professors
Associate Professors
Assistant Professors
Scientific Investigators OPI
Contract Investigators “Ramón y Cajal” programme
Other Contract Scientist Graduated Technicians CSIC
Contract Technicians
Specialized Technicians OPI
Research Assistants
Laboratory Assistants
2
8
8
0
2
2
1
2
5
4
0
11
6
11
0
0
2
5
1
4
4
0
3444
Total
Men
Professors
Other Contract Scientist
Graduated Technicians CSIC
Research Assistants
Women
Professors
Cont. Invest. “Ramón y Cajal” programme
Other Contract Scientist
Graduated Technicians CSIC
Research Assistants
204
Figures
Summary of economic data
Concept
20132014
Ordinary Budget 421 625.24 514 002.45
Support to Infrastructures 114 923.04 118 823.45
Projects and Contracts, Total
848 442.06
929 437.18
1,384 990.34 Total
2013
1,562 263.08
Ordinary Budget and
Support to Infrastructures
Projects and
Contracts, Total
Ordinary Budget and
Support to Infrastructures
2014
Projects and
Contracts, Total
205
Figures
CONSEJO SUPERIOR
DE INVESTIGACIONES
CIENTÍFICAS
SERRANO 119
28006 MADRID

Untitled - Instituto de Química Física Rocasolano

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