Resistance of bacteria to current antibiotics is an alarming health problem. In this sense, Pseudomonas represents a genus of Gram-negative pathogens, which has emerged as one of the most dangerous species causing nosocomial infections. Despite the effort of the scientific community, drug resistant strains of bacteria belonging to Pseudomonas spp. prevail. The high costs associated to drug discovery and the urgent need for more efficient antimicrobial chemotherapies envisage the fact that computer-aided methods can rationalize several stages involved in the development of a new drug. In this work, we introduce a chemoinformatic methodology devoted to the construction of a multitasking model for quantitative-structure biological effect relationships (mtk-QSBER). The purpose of this model was to perform simultaneous predictions of anti-Pseudomonas activities and ADMET (absorption, distribution, metabolism, elimination, and toxicity) properties of organic compounds. The mtk-QSBER model was created from a large and heterogeneous dataset (more than 54000 cases) and displayed accuracies higher than 90% in both training and prediction sets. In order to demonstrate the applicability of our mtk-QSBER model, we used the investigational antibacterial drug delafloxacin as a case of study, for which experimental results were recently reported. The predictions performed for many biological effects of this drug exhibited a remarkable convergence with the experimental assays, confirming that our model can serve as useful tool for virtual screening of potent and safer anti-Pseudomonas agents.

A detailed investigation of the dilute solutions of several imidazolium-based ([BMIM][Br], [EMIM][BF4], [BMIM][BF4], [HexMIM][BF4], [BMIM][Tf]) and pyridinium-based ([BMP][BF4]) ionic liquids, and two tetraalkylammonium salts (Bu4NBr and Bu4NBPh4) in methanol was carried out between 278.15 and 328.15 K. The limiting molar and ionic association constants were derived using the Lee-Wheaton equation. The limiting molar conductivity for room-temperature ionic liquids with common anion ([BF4]-) is found to obey the Stokes' law: Λ0 increases as the cation size decreases. Ionic association in all studied systems does not show definite correlation with cation structure, while it strongly depends on anion size and structure. Ion association constants are discussed and the role of non-Coulombic forces is demonstrated with the help of short-range square-mound potential. Performed data analysis indicates the formation of contact ion pair of similar structure in studied solutions of ionic liquids, with anion coordinated by imidazole or pyridine ring. The formation of H-bonding between bromide-anion and hydroxy-group of methanol was observed.

Recent analyses have highlighted the promotion of cancer migration and invasion, mediated through HDAC via MMP-2 and MMP-9. Since both class 1 HDACs and MMP-2/9 are involved in the migration and invasion of cancer, an attempt has been taken to design dual MMP-2/HDAC-8 inhibitors by pharmacophore mapping and molecular docking approaches. The designed molecules were synthesized and showed a range of inhibitory activity against different MMP subtypes. Most of these designed compounds were selective towards MMP-2 but less potent against anti-targets like MMP-8, -12, etc. The highly active MMP-2 inhibitors were also found to be active towards HDAC-8 but less potent against other class 1 HDACs (HDAC-1 and -2). Molecular dynamics simulations revealed that the designed compounds may be acting through a distinct mechanism of action in the 'acetate ion channel' of HDAC-8. Some potent dual MMP-2/HDAC-8 inhibitors were further explored for in vitro cellular assays against human lung carcinoma cell line A549. These analyses revealed that some of these dual inhibitors have considerable anti-migratory and anti-invasive properties. The work may help to obtain some useful dual inhibitors. © 2015 Royal Society of Chemistry.

The host-guest chemistry of ferrocene derivatives was explored by a combined experimental and theoretical study. Several 1-arylferrocenes and 1,1'-diarylferrocenes were synthesized by the Suzuki-Miyaura cross-coupling reaction. The ability of these compounds to bind small cations in the gas phase was investigated experimentally by electrospray ionization mass spectrometry (ESI-MS). The results evidenced a noticeable ability of all 1,1'-diarylferrocenes studied to bind cations, while the same was not observed for the corresponding 1-arylferrocenes nor ferrocene. The 1,1'-diarylferrocene center dot center dot center dot cation relative interaction energies were evaluated by ESI-MS and quantum chemical calculations and showed that cation binding in these systems follows electrostatic trends. It was found that, due to their unique molecular shape and smooth torsional potentials, 1,1'-diarylferrocenes can act as molecular tweezers of small-sized cations in the gas phase.

The effect of replacing bis(trifluoromethylsulphonyl)imide ([NTf2]) by hexafluorophosphate ([PF6]) in room temperature ionic liquid (IL) 1-butyl-3-methylimidazolium bis(trifluoromethylsulphonyl)imide ([BMIm][NTf2]) confined between two gold interfaces is herein reported through molecular dynamics simulations using all-atom non-polarisable force-fields. Five systems were studied ranging from pure [BMIm][NTf2] to pure [BMIm][PF6], with [PF6] molar fractions of 0, 0.125, 0.25, 0.375 and 0.5. Special attention was drawn to investigate the impact of the [PF6] anion on the IL, in particular on the first layers of the liquid in close contact with the solid gold surface.

The self-association equilibrium, i.e. formation of noncovalent dimers; in two triphenylamine derivative TPD (N,N'-bis(3-methylphenyl)-N,N'-diphenylbenzidine) and mMTDAB (1,3,5-tri[(3-methylphenyl)phenylamino]benzene), in solution was evaluated by H-1 NMR. spectroscopy. The gas-phase energetics of the respective dimerization processes was explored by computational quantum chemistry: The results indicate that self-association is significantly more extensive in TPB than in TDAB. It is proposed that this fact helps to explain why TPB presents a stability, higher than expected in the liquid phase, which is reflected in a lower melting temperature, a less volatile liquid, and possibly a higher tendency to form a glass. These results highlight the influence of self-association on the phase equilibria and thermodynamic properties of pure organic substances.