Gas-phase electronic and structural properties of the room temperature ionic liquid 1-ethyl-3-methylimidazolium tris(perfluoroethyl) trifluorophosphate ([EMIM][FAP]) were studied using density functional theory, and confirmed with results from infrared spectroscopy. A conformational analysis allowed the identification of several plausible conformers of the ion pairs. For the detected conformers, the infrared spectra were predicted and their thermodynamic properties were evaluated. The topology of the electronic density of the most stable conformers of [EMIM][FAP] ion pairs were characterised using the quantum theory of atoms in molecules. A number of possible hydrogen bonds between the cations and anions of the ionic liquid were identified. Excellent correspondence was found between the predicted spectra of gas-phase [EMIM][FAP] conformers and the experimental infrared spectrum, which in turn allowed a clear attribution of the vibration modes of [EMIM][FAP]. Finally, the contribution of the various conformers of both isomers of the [FAP](-) anion to the ionic liquid macro-properties is shown.

Aromatase is a multienzyme complex overexpressed in breast cancer and responsible for estrogen production. It is the potential target for designing anti-breast cancer drugs. Ligand and Structure-Based Drug Designing approaches (LBDD and SBDD) are involved in development of active and more specific Nonsteroidal Aromatase Inhibitors (NSAIs). Different LBDD and SBDD approaches are presented here to understand their utility in designing novel NSAIs. It is observed that molecules should possess a five or six membered heterocyclic nitrogen containing ring to coordinate with heme portion of aromatase for inhibition. Moreover, one or two hydrogen bond acceptor features, hydrophobicity, and steric factors may play crucial roles for anti-aromatase activity. Electrostatic, van der Waals, and Π-Π interactions are other important factors that determine binding affinity of inhibitors. HQSAR, LDA-QSAR, GQSAR, CoMFA, and CoMSIA approaches, pharmacophore mapping followed by virtual screening, docking, and dynamic simulation may be effective approaches for designing new potent anti-aromatase molecules.

Background: Virtual Screening methodologies have emerged as efficient alternatives for the discovery of new drug candidates. At the same time, ensemble methods are nowadays frequently used to overcome the limitations of employing a single model in ligand-based drug design. However, many applications of ensemble methods to this area do not consider important aspects related to both virtual screening and the modeling process. During the application of ensemble methods to virtual screening the proper validation of the models in virtual screening conditions is often neglected. No analysis of the diversity of the ensemble members is performed frequently or no considerations regarding the applicability domain of the base models are being made. Methods: In this research, we review basic concepts and definitions related to virtual screening. We comment recent applications of ensemble methods to ligand-based virtual screening and highlight their advantages and limitations. Results: Next, we propose a method based on genetic algorithms optimization for the generation of virtual screening tailored ensembles which address the previously identified problems in the current applications of ensemble methods to virtual screening. Conclusion: Finally, the proposed methodology is successfully applied to the generation of ensemble models for the ligand-based virtual screening of dual target A2A adenosine receptor antagonists and MAO-B inhibitors as potential Parkinson's disease therapeutics.

The ultraviolet-visible spectroscopy has been assessed as a technique for the evaluation of the strength of template-precursor adduct in the development of molecular imprints of the non-steroidal anti-inflammatory drug naproxen (NAP). The commonly employed approach relies on the collection of UV spectra of drug + precursor mixtures at different proportions, the spectra being recorded against blanks containing the same concentration of the precursor. The observation of either blue or red band-shifts and abatement of a major band are routinely attributed to template-precursor adduct formation. Following the described methodology, the precursors 1-(triethoxysilylpropyl)-3-(trimethoxysilylpropyl)-4,5-dihydroimidazolium iodide (AO-DHI+) and 4-(2-(trimethoxysilyl)ethyl)pyridine (PETMOS) provoked a blue-shift and band abatement effect on the NAP spectrum. Molecular dynamics simulations indicated a reasonable affinity between NAP and these precursors (coordination numbers 033 for AO-DHI+ and 0.18 for PETMOS), hence showing that NAP-precursor complexation is in fact effective. However, time dependent density functional theory (TD-DFT) calculations of the spectra of both free and precursor-complexed NAP were identical, thus providing no theoretical basis for the complexation-induced effects observed. We realized that the intense spectral bands of AO-DHI+ and PETMOS (at around 265 nm) superimpose partially with the NAP bands, and the apparent "blue-shifting" in the NAP spectra when mixed with AO-DHI + and PETMOS was in this case a spurious effect of the intense background subtraction. Therefore, extreme care must be taken when interpreting other spectroscopic results obtained in a similar fashion.

Density functional theory (DFT) calculations were employed to study the dissociation of the O-H bond in methanol on several planar and stepped bimetallic transition metal surfaces, composed of elements showing high or moderate activity towards this reaction, namely, Ni, Rh, Ru, Ir, Pd, Au, Zn and Cu. The activation energies for the O-H bond cleavage were compared with those estimated using a Bronsted-Evans-Polanyi (BEP) relationship for the RO-H bond breakage on pure metal transition surfaces, relating the activation energy for the reaction with the adsorption energies of the reaction products, RO center dot and H-center dot adsorbed on the surface of the catalyst. Furthermore, the average differences between the values of the activation energies calculated with the exhaustive determination of the full reaction path and location of the transition state on each surface model and the activation energies obtained from the BEP relationship with the simple calculation of the adsorption energies of the RO center dot and H-center dot species are similar to 0.14 eV. This suggests that the BEP relationship developed upon the consideration of data for dissociation of the O-H bond in alcohols and water on pure metal surfaces is also valid for a qualitative prediction of the methanol activation energy on bimetallic surfaces.

In the past few years, the sol-gel polycondensation technique has been increasingly employed with great success as an alternative approach to the preparation of molecularly imprinted materials (MIMs). The main aim of this study was to study, through a series of molecular dynamics (MD) simulations, the selectivity of an imprinted silica xerogel towards a new templatethe (+/-)-2-(P-Isobutylphenyl) propionic acid (Ibuprofen, IBU). We have previously demonstrated the affinity of this silica xerogel toward a similar molecule. In the present study, we simulated the imprinting process occurring in a sol-gel mixture using the Optimized Potentials for Liquid Simulations-All Atom (OPLS-AA) force field, in order to evaluate the selectivity of this xerogel for a template molecule. In addition, for the first time, we have developed and verified a new parameterisation for the Ibuprofen((R)) based on the OPLS-AA framework. To evaluate the selectivity of the polymer, we have employed both the radial distribution functions, interaction energies and cluster analyses.

In this work, the effect of temperature on the contact angle of a water droplet on grafted thermoresponsive poly-(N-isopropylacrylamide) (PNIPAAm) polymer brushes is studied using all-atom molecular dynamics simulations in the temperature range of 270-330 K. A shift from 551 to 65 degrees in contact angle values is observed as the temperature increases from 300 K to 310 K, which is in line with the experimental reports. The behavior of a water droplet on PNIPAAm brushes is analyzed using hydrogen bond analysis, water diffusion, radial distribution functions, the potential of mean force, excess entropy and the second virial coefficient (B-2). The thermo-responsive behavior of PNIPAAm brushes, quantified using the excess entropy and B-2 of PNIPAAm-water and water-water interactions, is mainly governed by polymer-water interactions. In particular, the excess entropy and B-2 of PNIPAAm resulting from the PNIPAAm-water interactions are found to increase with increasing temperature. The dehydration of PNIPAAm brushes and the increase in the contact angle of water were confirmed to be entropy driven processes.