In this paper we present results of a detailed and systematic molecular dynamics study of the water/nitrobenzene interface. Using a simple procedure to eliminate fluctuations of the interface position, we are able to obtain true intrinsic profiles for several properties (density, hydrogen bonds, molecular orientation, etc.) in the direction perpendicular to the interfacial plane. Our results show that both water and organic inter-facial molecules form a tightly packed layer oriented parallel to the interface, with reduced mobility in the perpendicular direction. Beyond this layer, water quickly restores its bulk structure, while nitrobenzene exhibits structural anisotropies that extend further into the bulk region: Water molecules that protrude farthest into the organic phase point one hydrogen atom in the direction perpendicular to the interface, forming a hydrogen bond with a nitrobenzene oxygen. By fitting both the global and the intrinsic density profiles, we obtain estimates for the total and intrinsic interface widths, respectively. These are combined with capillary wave theory to produce a self-consistent method for the calculation of the inter-facial tension. Values calculated using this method are in very good agreement with direct calculations from the components of the pressure tensor.

Understanding the synthesis of periodic mesoporous silica (PMS) is crucial for a more efficient use of these materials and is a necessary first step toward a rational design strategy for the templated synthesis of porous solids. In this paper, the early stages of the synthesis process of PMS materials are simulated directly by molecular dynamics, using realistic atomistic models. It is the first time that such computationally demanding calculations have been attempted. By comparing the self-assembly of cationic surfactants in the presence and absence of silicates, we are able to show that silica promotes the formation of larger aggregates than in a simple surfactant/water solution. The formation of these larger micelles is explained by a strong interaction of the silicate molecules with the surfactant head groups. This strong interaction increases the local concentration of silica at the surface of the micelles, which induces the formation of more condensed silicate species. The surfactant/silica structures observed here are potentially important intermediates in PMS synthesis.

The cancer research community has begun to address the in silico modeling approaches, such as quantitative structure-activity relationships (QSAR), as an important alternative tool for screening potential anticancer drugs. With the compilation of a large dataset of nucleosides synthesized in our laboratories, or elsewhere, and tested in a single cytotoxic assay under the same experimental conditions, we recognized a unique opportunity to attempt to build predictive QSAR models. Here, we report a systematic evaluation of classification models to probe anticancer activity, based on linear discriminant analysis along with 2D-molecular descriptors. This strategy afforded a final QSAR model with very good overall accuracy and predictability on external data. Finally, we search for similarities between the natural nucleosides, present in RNA/DNA, and the active nucleosides well-predicted by the model. The structural information then gathered and the QSAR model per se shall aid in the future design of novel potent anticancer nucleosides.

QTAIM atomic and bond properties, ionization potential, and O-H bond dissociation energies calculated at the B3LYP/6-311++G(2d,2p) level indicate the natural chalcones bear a significant radical scavenging activity. However, their ionization potentials indicate they decrease the electron-transfer rate between antioxidant and oxygen that yields the pro-oxidative cations less than other natural antioxidants. Rings A and B display slight and similar positive charges, whereas ring B is involved in exocycle delocalization at a larger extension.

Prevention of environmentally induced cancers is a major health problem of which solutions depend on the rapid and accurate screening of potential chemical hazards. Lately, theoretical approaches such as the one proposed here - Quantitative Structure-Activity Relationship (QSAR) are increasingly used for assessing the risks of environmental chemicals, since they can markedly reduce costs, avoid animal testing, and speed up policy decisions. This paper reports a QSAR study based on the Topological Substructural Molecular Design (TOPS-MODE) approach, aiming at predicting the rodent carcinogenicity of a set of nitroso-compounds selected from the Carcinogenic Potency Data Base (CPDB). The set comprises nitrosoureas (14 chemicals), N-nitrosamines (18 chemicals) C-nitroso-compounds (1 chemical), nitrosourethane (1 chemical) and nitrosoguanidine (1 chemical), which have been bioassayed in male rat using gavage as the route of administration. Here we are especially concerned in gathering the role of both parameters on the carcinogenic activity of this family of compounds. First, the regression model was derived, upon removal of one identified nitrosamine outlier, and was able to account for more than 84% of the variance in the experimental activity. Second, the TOPS-MODE approach afforded the bond contributions - expressed as fragment contributions to the carcinogenic activity - that can be interpreted and provide tools for better understanding the mechanisms of carcinogenesis. Finally, and most importantly, we demonstrate the potentialities of this approach towards the recognition of structural alerts

Diffusion Monte Carlo calculations are performed for ground and excited rotational states of HX(He-4)(N), complexes with N <= 20 and X = F, Cl, Br. The calculations are done using ab initio He-HX intermolecular potentials whose computation is described. Intermolecular energies and He radial and angular probability density distributions are computed as a function of the number of solvent atoms. Excited states are calculated using fixed-node diffusion Monte Carlo methods, and molecule-solvent angular momentum coupling is studied as a function of cluster size and potential anisotropy. Nodal surfaces of the many-body wave function are computed approximately by making an adiabatic Born-Oppenheimer-like separation of radial and angular degrees of freedom of the cluster. This procedure is extended to include radial dependencies in the adiabatic nodal function. We predict that the observed decrease in the gas-phase rotational constants for HCl and HBr in a He-4 nanodroplet will be smaller than that observed for HF, despite HF's having the largest (by far) gas-phase rotational constant of the three molecules. This suggests that the specifics of the solvation dynamics of a molecule in a 4 He cluster are the result of a delicate interplay between the magnitude of the gas-phase rotational constant of the molecule and the anisotropic contributions to the atom-molecule potential energy.

Cytochromes P450 (CYPs) comprise a superfamily of enzymes involved in various physiological functions, including the metabolism of drugs and carcinogenic compounds present in food, making them of great importance for human health. The possibility that CYPs could be broadening or changing substrate specificity in accordance to the high diversity of xenobiotics compounds environmentally available suggests that their metabolic function could be under adaptive evolution. We evaluated the existence of functional divergence and signatures of selection on mammalian genes from the drug-metabolizing CYP2 family. Thirteen of the sites found to be functionally divergent and the eight found to be under strong positive selection occurred in important functional domains, namely on the substrate entrance channel and within the active site. Our results provide insight into CYPs evolution and the role of molecular adaptation in enzyme substrate-specificity diversification.

R/S-3,4-Dihydro-2,2-dimethyl-6-halo-4-(substituted phenylaminocarbonyl- amino)-2H-1-benzopyrans are pancreatic β-cells potassium. (K ATP-pβ) channel openers with inhibitory effect on insulin secretion. To find the more active and effective benzopyrans as selective potassium (KATP-pβ) channel openers towards the pancreatic tissues, quantitative structure-activity relationships (QSAR) study was performed using E-state and R-state indices along with Wang-Ford charges, n-octanol/water partition coefficient, molar refractivity, and indicator parameters. QSAR models were developed by statistical techniques, e.g., multiple linear regression (MLR), principle component regression, analysis (PCRA), and partial least squares (PLS) analysis. The generated equations were validated by the leave-one-out cross-validation method. The models show the importance of ETSA indices of atom numbers 16, 17, 18, 19, 21 as well as 22. The positive coefficient of S16, S17, S18, S19, S21, and S22 indicate that with the increase of the value of E-state indices, desired activity decreases. RTSA index is also important for the biological activity, and the atom numbers 16, 17, 18, 19, 20 and 22 are involved in van der Waals interactions. RTSA index also possesses negative impact on the inhibition of residual insulin secretion. Wang-Ford charges of some particular atoms are also important for the inhibition. Increase of n-octanol/water partition coefficients of compounds inhibit insulin secretion, and the presence of chlorine atom at m- and p- positions of the phenyl ring B is necessary for the inhibition of residual insulin secretion. © 2007 NRC Canada.