Solvent effects on the π* shape resonances of uracil.

We have investigated the effect of microsolvation on the π* shape resonances of uracil, referred to as π1 * and π2 * in the order of increasing energy. Our study considered uracil-water aggregates with six solvent molecules obtained from Monte Carlo simulations in the liquid phase. To explore the ensemble statistics, we combined scattering calculations, performed in the static exchange and static exchange plus polarization approximations, with linear regressions of virtual orbital energies to the scattering results. In general, the solvent molecules stabilize the anion states, and the lower lying π1 * resonance becomes a bound state in most of the solute-water clusters. We also discuss how the strength of the H bonds can affect the energies of the anion states, in addition to the number and donor/acceptor characters of those bonds. The thermal distributions for the vertical attachment energies, obtained from 133 statistically uncorrelated solute-solvent clusters, are significantly broad in the energy scale of the autoionization widths. The distributions for the π1 * and π2 * anion states slightly overlap, thus giving rise to a quasi-continuum of attachment energies below ≲2.5 eV, in contrast to the gas phase picture of electron attachment to well separated resonances below the electronic excitation threshold. Both the stabilization of the anion states and the spread of attachment energies could be expected to favor the dissociative electron attachment processes believed to underlie the electron-induced damage to biomolecules.

Membrane negative curvature induced by a hybrid peptide from pediocin PA-1 and plantaricin 149 as revealed by atomistic molecular dynamics simulations.

Antimicrobial peptides (AMPs) are cationic peptides that kill bacteria with a broad spectrum of action, low toxicity to mammalian cells and exceptionally low rates of bacterial resistance. These features have led to considerable efforts in developing AMPs as an alternative antibacterial therapy. In vitro studies have shown that AMPs interfere with membrane bilayer integrity via several possible mechanisms, which are not entirely understood. We have performed the synthesis, membrane lysis measurements, and biophysical characterization of a novel hybrid peptide. These measurements show that PA-Pln149 does not form nanopores, but instead promotes membrane rupture. It causes fast rupture of the bacterial model membrane (POPG-rich) at concentrations 100-fold lower than that required for the disruption of mammalian model membranes (POPC-rich). Atomistic molecular dynamics (MD) simulations were performed for single and multiple copies of PA-Pln149 in the presence of mixed and pure POPC/POPG bilayers to investigate the concentration-dependent membrane disruption by the hybrid peptide. These simulations reproduced the experimental trend and provided a potential mechanism of action for PA-Pln149. It shows that the PA-Pln149 does not form nanopores, but instead promotes membrane destabilization through peptide aggregation and induction of membrane negative curvature with the collapse of the lamellar arrangement. The sequence of events depicted for PA-Pln149 may offer insights into the mechanism of action of AMPs previously shown to induce negative deformation of membrane curvature and often associated with peptide translocation via non-bilayer intermediate structures.

One- and two-photon absorption of fluorescein dianion in water: a study using S-QM/MM methodology and ZINDO method.

One- and two-photon absorption (1PA and 2PA) of fluorescein dianion (FSD) in water were studied using a combined and sequential Quantum Mechanics/Molecular Dynamics methodology. Different sets of 250 statistically relevant (uncorrelated) configurations composed by the solute and several solvent molecules were sampled from the classical simulation. On these configurations, the electronic properties were calculated a posteriori using the Zerner's intermediate neglect of differential overlap (ZINDO) method. The linear and nonlinear absorption of FSD in water were calculated using discrete and explicit solvent models. In the largest case, the relevant configurations are composed by FSD and 47 explicit water molecules embedded in the electrostatic field of all remaining water molecules. Both INDO/CIS and INDO/CISD calculations were performed to study the absorption processes of FSD and the Sum-Over-States (SOS) model was used to describe the 2PA process. A semi-classical method for spectrum simulations was employed to simulate the 1PA and 2PA cross-section spectra of FSD in water. For comparison purposes, in the case of the 2PA process two approaches, the "full expression" and "resonant expression" methods, were employed to simulate the nonlinear spectrum. The last method assumes resonant conditions and on the computation point of view it represents an interesting option to study the 2PA process. The INDO/CI calculations give a satisfactory description of the 1PA spectrum of FSD and properly describe the unusual blue-shift of its first π→π(*) transition in water. In the case of 2PA, the introduction of doubly excited configuration interactions (INDO/CISD) has proven to be essential for an appropriate description of the process at the higher energy spectral region. It was observed that the solvent effects do not drastically change the cross-sections of both processes. The simulated 2PA cross-section spectrum provided by the "full expression" method presents a better definition of the bands which appear along the experimental spectrum than the one provided by the "resonant expression" method. However, both approaches provide similar description for the effect of the solvent environment on the 2PA process of FSD in water.

Isotropic magnetic shielding constants of retinal derivatives in aprotic and protic solvents.

We investigate the nuclear isotropic shielding constants σ((13)C) and σ((17)O) of isomers of retinoic acid and retinal in gas-phase and in chloroform, acetonitrile, methanol, and water solutions via Monte Carlo simulation and quantum mechanics calculations using the GIAO-B3LYP∕6-311++G(2d,2p) approach. Electronic solute polarization effects due to protic and aprotic solvents are included iteratively and play an important role in the quantitative determination of oxygen shielding constants. Our MP2∕6-31G+(d) results show substantial increases of the dipole moment of both retinal derivatives in solution as compared with the gas-phase results (between 22% and 26% in chloroform and between 55% and 99% in water). For the oxygen atoms the influence of the solute polarization is mild for σ((17)O) of hydroxyl group, even in protic solvents, but it is particularly important for σ((17)O) of carbonyl group. For the latter, there is a sizable increase in the magnitude with increasing solvent polarity. For the carbon atoms, the solvent effects on the σ((13)C) values are in general small, being more appreciable in carbon atoms of the polyene chain than in the carbon atoms of the ß-ionone ring and methyl groups. The results also show that isomeric changes on the backbones of the polyene chains have marked influence on the (13)C chemical shifts of carbon atoms near to the structural distortions, in good agreement with the experimental results measured in solution.

Electron collisions with the HCOOH···(H2O)n complexes (n = 1, 2) in liquid phase: the influence of microsolvation on the π* resonance of formic acid.

We report momentum transfer cross sections for elastic collisions of low-energy electrons with the HCOOH···(H2O)n complexes, with n = 1, 2, in liquid phase. The scattering cross sections were computed using the Schwinger multichannel method with pseudopotentials in the static-exchange and static-exchange plus polarization approximations, for energies ranging from 0.5 eV to 6 eV. We considered ten different structures of HCOOH···H2O and six structures of HCOOH···(H2O)2 which were generated using classical Monte Carlo simulations of formic acid in aqueous solution at normal conditions of temperature and pressure. The aim of this work is to investigate the influence of microsolvation on the π* shape resonance of formic acid. Previous theoretical and experimental studies reported a π* shape resonance for HCOOH at around 1.9 eV. This resonance can be either more stable or less stable in comparison to the isolated molecule depending on the complex structure and the water role played in the hydrogen bond interaction. This behavior is explained in terms of (i) the polarization of the formic acid molecule due to the water molecules and (ii) the net charge of the solute. The proton donor or acceptor character of the water molecules in the hydrogen bond is important for understanding the stabilization versus destabilization of the π* resonances in the complexes. Our results indicate that the surrounding water molecules may affect the lifetime of the π* resonance and hence the processes driven by this anion state, such as the dissociative electron attachment.

Polarization and spectral shift of benzophenone in supercritical water.

Monte Carlo simulation and quantum mechanics calculations based on the INDO/CIS and TD-DFT methods were utilized to study the solvatochromic shift of benzophenone when changing the environment from normal water to supercritical (P = 340.2 atm and T = 673 K) condition. Solute polarization increases the dipole moment of benzophenone, compared to gas phase, by 88 and 35% in normal and supercritical conditions, giving the in-solvent dipole value of 5.8 and 4.2 D, respectively. The average number of solute-solvent hydrogen bonds was analyzed, and a large decrease of 2.3 in normal water to only 0.8 in the supercritical environment was found. By using these polarized models of benzophenone in the two different conditions of water, we performed MC simulations to generate statistically uncorrelated configurations of the solute surrounded by the solvent molecules and subsequent quantum mechanics calculations on these configurations. When changing from normal to supercritical water environment, INDO/CIS calculations explicitly considering all valence electrons of the 235 solvent water molecules resulted in a solvatochromic shift of 1425 cm(-1) for the most intense pi-pi* transition of benzophenone, that is, slightly underestimated in comparison with the experimentally inferred result of 1700 cm(-1). TD-B3LYP/6-311+G(2d,p) calculations on the same configurations but with benzophenone electrostatically embedded in the 320 water molecules resulted in a solvatochromic shift of 1715 cm(-1) for this transition, in very good agreement with the experimental result. When using the unpolarized model of the benzophenone, this calculated solvatochromic shift was only 640 cm(-1). Additional calculations were also made by using BHandHLYP/6-311+G(2d,p) to analyze the effect of the asymptotic decay of the exchange functional. This study indicates that, contrary to the general expectation, there is a sizable solute polarization even in the low-density regime of supercritical condition and that the inclusion of this polarization is important for a reliable description of the spectral shifts considered here.

[Linkage of environmental and health data: health risk analysis of the Rio de Janeiro water supply by using geographical information systems]. / Inter-relacionamento de dados ambientais e de saúde: análise de risco á saúde aplicada ao abastecimento de água no Rio de Janeiro utilizando Sistemas de Informações Geográficas.

Exposure assessment of population groups is based on linkage of environmental and health data. This relationship can be hard to establish due to spatial and temporal lags in data sets. Environmental data generally refer to scattered sampling points, while epidemiological data integrate periods of time within administrative territories. GIS can be used as a basis for organizing health-related and environmental data sets. We examined potential health risk in the Rio de Janeiro city water supply based on the overlay of information layers containing data on the presence and quality of water supply services. We used census tracts as the primary georeferenced data, since they contain information on how households are supplied, water supply pipes, sources, and reservoirs, and water quality according to the monitoring program. Population groups exposed to risks were located and quantified using spatial operations among these layers and adopting different risk criteria. The main problems related to water supply are located on the northern slope of the Tijuca Mountain Range (involving the absence or poor quality of water) and in the western area of the city of Rio, where the population relies on alternative water supply sources. The different origins, objectives, and structures of data have to be analyzed critically, and GIS can be used as a data validation tool as well as an instrument for detailed identification of inconsistencies.

Simulation studies of self-replicating oligoribotides, with a proposal for the transition to a peptide-assisted stage.

A two-substrate Michaelis-Menten mechanism previously proposed for the self-replication of RNA-like oligomers is developed. Differential growth depends on the existence of two pairs of complementary monomers and leads to 2n groups of 2n components each (n is the oligomer size). As n increases the 2n groups tend to overlap with one another, and the efficiency of the process to increase the information content of the strands decreases. In a second stage we suppose that randomly synthesized peptides with one predominant amino acid interacted with the ribotides, increasing the growth rate of some of them, and at the same time had their mean life increased by interactions with other ribotides of the same kinetic group. Natural selection could have preserved a favourable codon-anticodon-amino acid correlation, the precursor of the modern genetic code.