RESUMO
We introduce a nanofluidic platform that can be used to carry out femtosecond electron diffraction (FED) and transmission electron microscopy (TEM) measurements in liquid samples or in-liquid specimens, respectively. The nanofluidic cell (NFC) system presented herein has been designed to withstand high sample refreshing rates (over one kilohertz), a prerequisite to succeed with FED experiments in our lab. Short beam paths, below 1 µm, in combination with ultrathin membranes (less than 100 nm thick) are necessary conditions for in-liquid FED and TEM studies due to the strongly interacting nature of electrons. Depending on the application, the beam path in our NFC can be tuned between 50 nm and 10 µm with ultrathin stoichiometric silicon nitride (Si3N4) windows as thin as 20 nm. Stoichiometric Si3N4 has been selected to reduce membrane bulging owing to its higher tensile stress and transparency in the UV-vis-NIR region to allow for laser excitation in FED experiments. Key design parameters and improvements made over previous NFC systems are discussed, and some preliminary electron images obtained by 200 kV scanning TEM are presented.
RESUMO
Tyrosine nitration is an oxidative post-translational modification that can occur in proteins associated to hydrophobic bio-structures such as membranes and lipoproteins. In this work, we have studied tyrosine nitration in membranes using a model system consisting of phosphatidylcholine liposomes with pre-incorporated tyrosine-containing 23 amino acid transmembrane peptides. Tyrosine residues were located at positions 4, 8 or 12 of the amino terminal, resulting in different depths in the bilayer. Tyrosine nitration was accomplished by exposure to peroxynitrite and a peroxyl radical donor or hemin in the presence of nitrite. In egg yolk phosphatidylcholine liposomes, nitration was highest for the peptide with tyrosine at position 8 and dramatically increased as a function of oxygen levels. Molecular dynamics studies support that the proximity of the tyrosine phenolic ring to the linoleic acid peroxyl radicals contributes to the efficiency of tyrosine oxidation. In turn, α-tocopherol inhibited both lipid peroxidation and tyrosine nitration. The mechanism of tyrosine nitration involves a "connecting reaction" by which lipid peroxyl radicals oxidize tyrosine to tyrosyl radical and was fully recapitulated by computer-assisted kinetic simulations. Altogether, this work underscores unique characteristics of the tyrosine oxidation and nitration process in lipid-rich milieu that is fueled via the lipid peroxidation process.
Assuntos
Membrana Celular/metabolismo , Radicais Livres/metabolismo , Peroxidação de Lipídeos , Peptídeos/metabolismo , Ácido Peroxinitroso/metabolismo , Tirosina/metabolismo , Amidinas/metabolismo , Sequência de Aminoácidos , Membrana Celular/química , Hemina/metabolismo , Lipossomos/química , Lipossomos/metabolismo , Simulação de Dinâmica Molecular , Oxirredução , Oxigênio/metabolismo , Peptídeos/química , Tirosina/químicaRESUMO
MOTIVATION: Water molecules are key players for protein folding and function. On the protein surface, water is not placed randomly, but display instead a particular structure evidenced by the presence of specific water sites (WS). These WS can be derived and characterized using explicit water Molecular Dynamics simulations, providing useful information for ligand binding prediction and design. Here we present WATCLUST, a WS determination and analysis tool running on the VMD platform. The tool also allows direct transfer of the WS information to Autodock program to perform biased docking. AVAILABILITY AND IMPLEMENTATION: The WATCLUST plugin and documentation are freely available at http://sbg.qb.fcen.uba.ar/watclust/. CONTACT: marcelo@qi.fcen.uba.ar, adrian@qi.fcen.uba.ar.
Assuntos
Desenho de Fármacos , Proteínas/química , Software , Água/química , Proteínas de Escherichia coli/química , Simulação de Dinâmica MolecularRESUMO
Trypanosoma cruzi, the causative agent of Chagas disease, contains exclusively iron-dependent superoxide dismutases (Fe-SODs) located in different subcellular compartments. Peroxynitrite, a key cytotoxic and oxidizing effector biomolecule, reacted with T. cruzi mitochondrial (Fe-SODA) and cytosolic (Fe-SODB) SODs with second order rate constants of 4.6 ± 0.2 × 10(4) M(-1) s(-1) and 4.3 ± 0.4 × 10(4) M(-1) s(-1) at pH 7.4 and 37 °C, respectively. Both isoforms are dose-dependently nitrated and inactivated by peroxynitrite. Susceptibility of T. cruzi Fe-SODA toward peroxynitrite was similar to that reported previously for Escherichia coli Mn- and Fe-SODs and mammalian Mn-SOD, whereas Fe-SODB was exceptionally resistant to oxidant-mediated inactivation. We report mass spectrometry analysis indicating that peroxynitrite-mediated inactivation of T. cruzi Fe-SODs is due to the site-specific nitration of the critical and universally conserved Tyr(35). Searching for structural differences, the crystal structure of Fe-SODA was solved at 2.2 Å resolution. Structural analysis comparing both Fe-SOD isoforms reveals differences in key cysteines and tryptophan residues. Thiol alkylation of Fe-SODB cysteines made the enzyme more susceptible to peroxynitrite. In particular, Cys(83) mutation (C83S, absent in Fe-SODA) increased the Fe-SODB sensitivity toward peroxynitrite. Molecular dynamics, electron paramagnetic resonance, and immunospin trapping analysis revealed that Cys(83) present in Fe-SODB acts as an electron donor that repairs Tyr(35) radical via intramolecular electron transfer, preventing peroxynitrite-dependent nitration and consequent inactivation of Fe-SODB. Parasites exposed to exogenous or endogenous sources of peroxynitrite resulted in nitration and inactivation of Fe-SODA but not Fe-SODB, suggesting that these enzymes play distinctive biological roles during parasite infection of mammalian cells.
Assuntos
Proteínas de Protozoários/metabolismo , Superóxido Dismutase/metabolismo , Trypanosoma cruzi/enzimologia , Animais , Sítios de Ligação/genética , Western Blotting , Domínio Catalítico , Doença de Chagas/parasitologia , Cristalografia por Raios X , Cisteína/química , Cisteína/genética , Cisteína/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Transporte de Elétrons , Ativação Enzimática/efeitos dos fármacos , Interações Hospedeiro-Parasita , Isoenzimas/química , Isoenzimas/genética , Isoenzimas/metabolismo , Cinética , Modelos Moleculares , Simulação de Dinâmica Molecular , Mutagênese Sítio-Dirigida , Nitratos/metabolismo , Ácido Peroxinitroso/química , Ácido Peroxinitroso/metabolismo , Ácido Peroxinitroso/farmacologia , Ligação Proteica , Estrutura Secundária de Proteína , Proteínas de Protozoários/química , Proteínas de Protozoários/genética , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/química , Superóxido Dismutase/genética , Trypanosoma cruzi/genética , Trypanosoma cruzi/fisiologia , Tirosina/química , Tirosina/genética , Tirosina/metabolismoRESUMO
Many pathogenic microorganisms have evolved hemoglobin-mediated nitric oxide (NO) detoxification mechanisms, where a globin domain in conjunction with a partner reductase catalyzes the conversion of toxic NO to innocuous nitrate. The truncated hemoglobin HbN of Mycobacterium tuberculosis displays a potent NO dioxygenase activity despite lacking a reductase domain. The mechanism by which HbN recycles itself during NO dioxygenation and the reductase that participates in this process are currently unknown. This study demonstrates that the NADH-ferredoxin/flavodoxin system is a fairly efficient partner for electron transfer to HbN with an observed reduction rate of 6.2 µM/min(-1), which is nearly 3- and 5-fold faster than reported for Vitreoscilla hemoglobin and myoglobin, respectively. Structural docking of the HbN with Escherichia coli NADH-flavodoxin reductase (FdR) together with site-directed mutagenesis revealed that the CD loop of the HbN forms contacts with the reductase, and that Gly(48) may have a vital role. The donor to acceptor electron coupling parameters calculated using the semiempirical pathway method amounts to an average of about 6.4 10(-5) eV, which is lower than the value obtained for E. coli flavoHb (8.0 10(-4) eV), but still supports the feasibility of an efficient electron transfer. The deletion of Pre-A abrogated the heme iron reduction by FdR in the HbN, thus signifying its involvement during intermolecular interactions of the HbN and FdR. The present study, thus, unravels a novel role of the CD loop and Pre-A motif in assisting the interactions of the HbN with the reductase and the electron cycling, which may be vital for its NO-scavenging function.
Assuntos
Hemoglobinas Anormais/metabolismo , Mycobacterium tuberculosis/metabolismo , Sequência de Bases , Primers do DNA , Transporte de Elétrons , Elétrons , Hemoglobinas Anormais/química , Hemoglobinas Anormais/genética , Simulação de Dinâmica Molecular , Mutagênese Sítio-Dirigida , Mycobacterium tuberculosis/química , Mycobacterium tuberculosis/enzimologia , Oxirredução , Reação em Cadeia da PolimeraseRESUMO
A wealth of evidence indicates that lipid rafts are involved in the fusion of the viral lipid envelope with the target cell membrane. However, the interplay between these sterol- and sphingolipid-enriched ordered domains and viral fusion glycoproteins has not yet been clarified. In this work we investigate the molecular mechanism by which a membranotropic fragment of the glycoprotein gH of the Herpes Simplex Virus (HSV) type I (gH625) drives fusion of lipid bilayers formed by palmitoyl oleoyl phosphatidylcholine (POPC)-sphingomyelin (SM)-cholesterol (CHOL) (1 : 1 : 1 wt/wt/wt), focusing on the role played by each component. The comparative analysis of the liposome fusion assays, Dynamic Light Scattering (DLS), spectrofluorimetry, Neutron Reflectivity (NR) and Electron Spin Resonance (ESR) experiments, and Molecular Dynamics (MD) simulations shows that CHOL is fundamental for liposome fusion to occur. In detail, CHOL stabilizes the gH625-bilayer association by specific interactions with the peptide Trp residue. The interaction with gH625 causes an increased order of the lipid acyl chains, whose local rotational motion is significantly hampered. SM plays only a minor role in the process, favoring the propagation of lipid perturbation to the bilayer inner core. The stiffening of the peptide-interacting bilayer leaflet results in an asymmetric perturbation of the membrane, which is locally destabilized thus favoring fusion events. Our results show that viral fusion glycoproteins are optimally suited to exert a high fusogenic activity on lipid rafts and support the relevance of cholesterol as a key player of membrane-related processes.
Assuntos
Colesterol/química , Bicamadas Lipídicas/química , Peptídeos/química , Proteínas do Envelope Viral/química , Proteínas Virais/química , Glicoproteínas/química , Simulação de Dinâmica Molecular , Fosfatidilcolinas/química , Estrutura Terciária de Proteína , Esfingomielinas/químicaRESUMO
BACKGROUND: Thyroxine-binding globulin (TBG) is a non-inhibitory member of the serpin family of proteins whose main structural element is the reactive center loop (RCL), that, upon cleavage by proteases, is inserted into the protein core adopting a ß-strand conformation (stressed to relaxed transition, S-to-R). After S-to-R transition thyroxine (T4) affinity decreases. However, crystallographic studies in the presence or absence of the hormone in different states are unable to show significant differences in the structure and interactions of the binding site. Experimental results also suggest the existence of several S states (differing in the number of inserted RCL residues), associated with a differential affinity. METHODS: To shed light into the molecular basis that regulates T4 affinity according to the degree of RCL insertion in TBG, we performed extended molecular dynamics simulations combined with several thermodynamic analysis of the T4 binding to TBG in three different S states, and in the R state. RESULTS: Our results show that, despite T4 binding in the protein by similar interactions in all states, a good correlation between the degree of RCL insertion and the binding affinity, driven by a change in TBG conformational entropy, was observed. CONCLUSION: TBG allosteric regulation is entropy driven. The presence of multiple S states may allow more efficient T4 release due to protease activity. GENERAL SIGNIFICANCE: The presented results are clear examples of how computer simulation methods can reveal the thermodynamic basis of allosteric effects, and provide a general framework for understanding serpin allosteric affinity regulation.
Assuntos
Globulina de Ligação a Tiroxina/química , Tiroxina/química , Regulação Alostérica/fisiologia , Sítios de Ligação , Cristalografia por Raios X , Entropia , Humanos , Estrutura Secundária de Proteína , Tiroxina/metabolismo , Globulina de Ligação a Tiroxina/metabolismoRESUMO
Plasma membrane lipids significantly affect assembly and activity of many signaling networks. The present work is aimed at analyzing, by molecular dynamics simulations, the structure and dynamics of the CD3 ζζ dimer in palmitoyl-oleoyl-phosphatidylcholine bilayer (POPC) and in POPC/cholesterol/sphingomyelin bilayer, which resembles the raft membrane microdomain supposed to be the site of the signal transducing machinery. Both POPC and raft-like environment produce significant alterations in structure and flexibility of the CD3 ζζ with respect to nuclear magnetic resonance (NMR) model: the dimer is more compact, its secondary structure is slightly less ordered, the arrangement of the Asp6 pair, which is important for binding to the Arg residue in the alpha chain of the T cell receptor (TCR), is stabilized by water molecules. Different interactions of charged residues with lipids at the lipid-cytoplasm boundary occur when the two environments are compared. Furthermore, in contrast to what is observed in POPC, in the raft-like environment correlated motions between transmembrane and cytoplasmic regions are observed. Altogether the data suggest that when the TCR complex resides in the raft domains, the CD3 ζζ dimer assumes a specific conformation probably necessary to the correct signal transduction.
Assuntos
1,2-Dipalmitoilfosfatidilcolina/análogos & derivados , Complexo CD3/química , Bicamadas Lipídicas/química , Microdomínios da Membrana/química , 1,2-Dipalmitoilfosfatidilcolina/química , Sequência de Aminoácidos , Dimerização , Modelos Moleculares , Simulação de Dinâmica Molecular , Dados de Sequência Molecular , Homologia de Sequência de AminoácidosRESUMO
Among 20 p450s of Mycobacterium tuberculosis (Mt), CYP121 has received an outstanding interest, not only due to its essentiality for bacterial viability but also because it catalyzes an unusual carbon-carbon coupling reaction. Based on the structure of the substrate bound enzyme, several reaction mechanisms were proposed involving first Tyr radical formation, second Tyr radical formation, and C-C coupling. Key and unknown features, being the nature of the species that generate the first and second radicals, and the role played by the protein scaffold each step. In the present work we have used classical and quantum based computer simulation methods to study in detail its reaction mechanism. Our results show that substrate binding promotes formation of the initial oxy complex, Compound I is the responsible for first Tyr radical formation, and that the second Tyr radical is formed subsequently, through a PCET reaction, promoted by the presence of key residue Arg386. The final C-C coupling reaction possibly occurs in bulk solution, thus yielding the product in one oxygen reduction cycle. Our results thus contribute to a better comprehension of MtCYP121 reaction mechanism, with direct implications for inhibitor design, and also contribute to our general understanding of these type of enzymes.
Assuntos
Proteínas de Bactérias/química , Sistema Enzimático do Citocromo P-450/química , Simulação de Dinâmica Molecular , Mycobacterium tuberculosis/enzimologia , Dicetopiperazinas/química , Radicais Livres/química , Oxidantes/química , Oxirredução , Ligação Proteica , Teoria Quântica , Soluções , Termodinâmica , Tirosina/químicaRESUMO
Carbon monoxide releasing molecules (CORMs) have important bactericidal, anti-inflammatory, neuroprotective, and antiapoptotic effects and can be used as tools for CO physiology experiments, including studies on vasodilation. In this context, a new class of CO releasing molecules, based on pentachlorocarbonyliridate(III) derivative have been recently reported. Although there is a growing interest in the characterization of protein-CORMs interactions, only limited structural information on CORM binding to protein and CO release has been available to date. Here, we report six different crystal structures describing events ranging from CORM entrance into the protein crystal up to the CO release and a biophysical characterization by isothermal titration calorimetry, Raman microspectroscopy, and molecular dynamics simulations of the complex between a pentachlorocarbonyliridate(III) derivative and hen egg white lysozyme, a model protein. Altogether, the data indicate the formation of a complex in which the ligand can bind to different sites of the protein surface and provide clues on the mechanism of adduct formation and CO release.
Assuntos
Monóxido de Carbono/química , Irídio/química , Muramidase/química , Compostos Organometálicos/química , Monóxido de Carbono/metabolismo , Irídio/metabolismo , Simulação de Dinâmica Molecular , Muramidase/metabolismo , Compostos Organometálicos/síntese química , Compostos Organometálicos/metabolismoRESUMO
Recognition and complex formation between proteins and carbohydrates is a key issue in many important biological processes. Determination of the three-dimensional structure of such complexes is thus most relevant, but particularly challenging because of their usually low binding affinity. In silico docking methods have a long-standing tradition in predicting protein-ligand complexes, and allow a potentially fast exploration of a number of possible protein-carbohydrate complex structures. However, determining which of these predicted complexes represents the correct structure is not always straightforward. In this work, we present a modification of the scoring function provided by AutoDock4, a widely used docking software, on the basis of analysis of the solvent structure adjacent to the protein surface, as derived from molecular dynamics simulations, that allows the definition and characterization of regions with higher water occupancy than the bulk solvent, called water sites. They mimic the interaction held between the carbohydrate -OH groups and the protein. We used this information for an improved docking method in relation to its capacity to correctly predict the protein-carbohydrate complexes for a number of tested proteins, whose ligands range in size from mono- to tetrasaccharide. Our results show that the presented method significantly improves the docking predictions. The resulting solvent-structure-biased docking protocol, therefore, appears as a powerful tool for the design and optimization of development of glycomimetic drugs, while providing new insights into protein-carbohydrate interactions. Moreover, the achieved improvement also underscores the relevance of the solvent structure to the protein carbohydrate recognition process.
Assuntos
Carboidratos/química , Simulação de Dinâmica Molecular , Proteínas/química , Solventes/química , Sítios de Ligação , Galectinas/química , Ligantes , Simulação de Acoplamento Molecular , Ligação Proteica , Conformação Proteica , Estrutura Terciária de Proteína , Software , Água/química , Água/metabolismoRESUMO
Liquid cell electron microscopy (LCEM) has long suffered from irreproducibility and its inability to confer high-quality images over a wide field of view. LCEM demands the encapsulation of the in-liquid sample between two ultrathin membranes (windows). In the vacuum environment of the electron microscope, the windows bulge, drastically reducing the achievable resolution and the usable viewing region. Herein, we introduce a shape-engineered nanofluidic cell architecture and an air-free drop-casting sample loading technique, which combined, provide robust bulgeless imaging conditions. We demonstrate the capabilities of our stationary approach through the study of in-liquid model samples and quantitative measurements of the liquid layer thickness. The presented LCEM method confers high throughput, lattice resolution across the complete viewing window, and sufficient contrast for the observation of unstained liposomes, paving the way to high-resolution movies of biospecimens in their near native environment.
RESUMO
Since proteins are dynamic systems in living organisms, the employment of methodologies contemplating this crucial characteristic results fundamental to allow revealing several aspects of their function. In this work, we present results obtained using classical mechanical atomistic simulation tools applied to understand the connection between protein dynamics and ligand migration. Firstly, we will present a review of the different sampling schemes used in the last years to obtain both ligand migration pathways and the thermodynamic information associated with the process. Secondly, we will focus on representative examples in which the schemes previously presented are employed, concerning the following: i) ligand migration, tunnels, and cavities in myoglobin and neuroglobin; ii) ligand migration in truncated hemoglobin members; iii) NO escape and conformational changes in nitrophorins; iv) ligand selectivity in catalase and hydrogenase; and v) larger ligand migration: the P450 and haloalkane dehalogenase cases. This article is part of a Special Issue entitled: Protein Dynamics: Experimental and Computational Approaches.
Assuntos
Simulação por Computador , Proteínas/química , Sítios de Ligação , Ligantes , Modelos Moleculares , Simulação de Dinâmica MolecularRESUMO
Experimental studies in hemeproteins and model Tyr/Cys-containing peptides exposed to oxidizing and nitrating species suggest that intramolecular electron transfer (IET) between tyrosyl radicals (Tyr-O(·)) and Cys residues controls oxidative modification yields. The molecular basis of this IET process is not sufficiently understood with structural atomic detail. Herein, we analyzed using molecular dynamics and quantum mechanics-based computational calculations, mechanistic possibilities for the radical transfer reaction in Tyr/Cys-containing peptides in solution and correlated them with existing experimental data. Our results support that Tyr-O(·) to Cys radical transfer is mediated by an acid/base equilibrium that involves deprotonation of Cys to form the thiolate, followed by a likely rate-limiting transfer process to yield cysteinyl radical and a Tyr phenolate; proton uptake by Tyr completes the reaction. Both, the pKa values of the Tyr phenol and Cys thiol groups and the energetic and kinetics of the reversible IET are revealed as key physico-chemical factors. The proposed mechanism constitutes a case of sequential, acid/base equilibrium-dependent and solvent-mediated, proton-coupled electron transfer and explains the dependency of oxidative yields in Tyr/Cys peptides as a function of the number of alanine spacers. These findings contribute to explain oxidative modifications in proteins that contain sequence and/or spatially close Tyr-Cys residues.
Assuntos
Simulação por Computador , Cisteína/química , Peptídeos/química , Proteínas/química , Tirosina/química , Cisteína/metabolismo , Transporte de Elétrons , Radicais Livres/química , Cinética , Simulação de Dinâmica Molecular , Peptídeos/metabolismo , Proteínas/metabolismo , Teoria Quântica , Soluções , Tirosina/metabolismo , Água/químicaRESUMO
Hb S-São Paulo (SP) [HBB:c.20A>T p.Glu6Val; c.196A>G p.Lys65Glu] is a new double-mutant hemoglobin that was found in heterozygosis in an 18-month-old Brazilian male with moderate anemia. It behaves like Hb S in acid electrophoresis, isoelectric focusing and solubility testing but shows different behavior in alkaline electrophoresis, cation-exchange HPLC and RP-HPLC. The variant is slightly unstable, showed reduced oxygen affinity and also appeared to form polymers more stable than the Hb S. Molecular dynamics simulation suggests that the polymerization is favored by interfacial electrostatic interactions. This provides a plausible explanation for some of the reported experimental observations.
Assuntos
Anemia Falciforme/genética , Hemoglobina Falciforme/metabolismo , Oxigênio/metabolismo , Globinas beta/metabolismo , Substituição de Aminoácidos , Anemia Falciforme/metabolismo , Sequência de Bases , Cromatografia Líquida de Alta Pressão , Eletroforese , Hemoglobina Falciforme/química , Hemoglobina Falciforme/genética , Heterozigoto , Humanos , Lactente , Focalização Isoelétrica , Masculino , Simulação de Dinâmica Molecular , Dados de Sequência Molecular , Polímeros , Estabilidade Proteica , Solubilidade , Eletricidade Estática , Globinas beta/química , Globinas beta/genéticaRESUMO
Highly energetic ultrashort electron bunches have the potential to reveal the ultrafast structural dynamics in relatively thicker in-liquid samples. However, direct current voltages higher than 100 kV are exponentially difficult to attain as surface and vacuum breakdown become an important problem as the electric field increases. One of the most demanding components in the design of a high-energy electrostatic ultrafast electron source is the high voltage feedthrough (HVFT), which must keep the electron gun from discharging against ground. Electrical discharges can cause irreversible component damage, while voltage instabilities render the instrument inoperative. We report the design, manufacturing, and conditioning process for a new HVFT that utilizes ultra-high molecular weight polyethylene as the insulating material. Our HVFT is highly customizable and inexpensive and has proven to be effective in high voltage applications. After a couple of weeks of gas and voltage conditioning, we achieved a maximum voltage of 180 kV with a progressively improved vacuum level of 1.8 × 10-8 Torr.
RESUMO
The structure and dynamics of thyroxine (T4), distal and proximal conformers of 3',3,5-triiodo-l-thyronine (T3d and T3p), and 3,5-diiodo-l-thyronine (T2) upon interaction with DMPC membranes were analyzed by means of molecular dynamics simulations. The locations, the more stable orientations, and the structural changes adopted by the hormones in the lipid medium evidence that the progressive iodine substitution on the beta ring lowers both the possibility of penetration and the transversal mobility in the membrane. However, the results obtained for T3d show that the number of iodine atoms in the molecule is not the only relevant factor in the hormone behavior but also the orientation of the single iodine substitution. The electrostatic interactions between the zwitterion group of the hormones with specific groups in the hydrophilic region of the membrane as well as the organization of the alkyl chains around the aromatic beta ring of the hormone were evaluated in terms of several radial distribution functions.
Assuntos
Di-Iodotironinas/química , Dimiristoilfosfatidilcolina/química , Bicamadas Lipídicas/química , Tiroxina/química , Tri-Iodotironina/química , Simulação por Computador , Lipídeos/química , Modelos Moleculares , Estrutura Molecular , Eletricidade Estática , Água/químicaRESUMO
Multiply charged anions (MCAs) display unique photophysics and solvent-stabilizing effects. Well-known aqueous species such as SO42- and PO43- experience spontaneous electron detachment or charge-separation fragmentation in the gas phase owing to the strong Coulomb repulsion arising from the excess of negative charge. Thus, anions often present low photodetachment thresholds and the ability to quickly eject electrons into the solvent via charge-transfer-to-solvent (CTTS) states. Here, we report spectroscopic evidence for the existence of a repulsive Coulomb barrier (RCB) that blocks the ejection of "CTTS-like" electrons of the aqueous B12F122- dianion. Our spectroscopic experimental and theoretical studies indicate that despite the exerted Coulomb repulsion by the nascent radical monoanion B12F12-â¢aq, the photoexcited electron remains about the B12F12-⢠core. The RCB is an established feature of the potential energy landscape of MCAs in vacuo, which seems to extend to the liquid phase highlighting recent observations about the dielectric behavior of confined water.