Prediction of vapour-liquid equilibria for systems containing longer-chain alcohols and alkanes by various group-contribution methods

Comparisons are made of predicted excess free enthalpies provided by the parameters available for the ASOG model of Derr and Deal, the UNIFAC model of Fredenslund et al., and the CRG (chemical-reticular group-contribution) method of Neau and Péneloux. These methods are applied to predict vapour-liquid equilibria for alcohol-alkane systems having carbon numbers up to 16. Overall, the accuracy of prediction increases in the order UNIFAC, ASOG, CRG.     

Albidosides H and I,two new triterpene saponins from the barks of Acacia albida Del. (Mimosaceae)

Two new triterpene saponins, albidosides H (1) and I (2), along with the three known saponins were isolated from the barks of Acacia albida. Their structures were elucidated on the basis of extensive 1D- and 2D-NMR studies and mass spectrometry. Albidosides H (1) and I (2) were assayed for their cytotoxicity against HeLa and HL60 cells using MTT method.     

Novel method to detect the volumetric glass --> liquid transition at high pressures: glycerol as a test case

We report a novel method of detecting the glass --> liquid transition at high pressures, which comprises measuring the relative volume change incurred upon heating glassy samples into the liquid state. We show data on glycerol in the pressure range 0.050-1.00 GPa to demonstrate the viability of the method. The reversible glass --> liquid transition is observed by means of a kink in the relative volume change on heating the sample isobarically, which is attributed to the glass --> liquid transition temperature Tg. This kink can only be observed in the second and subsequent heating cycles since it is superposed by a compaction in the first heating cycle. The isobaric thermal expansivity beta, which is closely related to the first derivative of this curve, shows the features expected for a glass --> liquid transition, including a sharp rise of beta(glass) in a narrow temperature interval to beta(viscous liquid) and an accompanying overshoot effect. Both Tg and the size of the overshoot effect vary in accordance with theory upon changing the ratio of cooling to heating rates. From the shape of this curve the onset, inflection, overshoot peak, and endpoint of the glass --> liquid transition can be extracted, which can be employed to calculate the reduced glass transition width as a measure for the fragility of the liquid. Comparison with literature data allows quantifying the accuracy of the liquid's thermal expansivity beta to be at least +/-10%, while the error in beta is significantly larger for the expansivity of the glassy state. The reproducibility of the glass --> liquid transition temperature Tg is better than +/-2 K. Our glycerol data confirms literature studies showing a nonlinear increase of Tg with increasing pressure (approximately 35 K/GPa on average), which is accompanied by an increase in fragility.     

A fuzzy distance metric for measuring the dissimilarity of planar chromatographic profiles with application to denaturing gradient gel electrophoresis data from human skin microbes: demonstration of an individual and gender-based fingerprint

A newly devised fuzzy metric for measuring the dissimilarity between two planar chromatographic profiles is proposed in this paper. It does not require an accurately assigned sample-feature matrix and can cope with slight imprecision of the positional information. This makes it very suitable for 1-D techniques which do not have a second spectroscopic dimension to aid variable assignment. The usefulness of this metric has been demonstrated on a large data set consisting of nearly 400 samples from Denaturing Gradient Gel Electrophoresis (DGGE) analysis of microbes on human skin. The pattern revealed by this dissimilarity metric was compared with the one represented by a sample-feature matrix and highly consistent results were obtained. Several pattern recognition techniques have been applied on the dissimilarity matrix based on this dissimilarity metric. According to rank analysis, within-individual variation is significantly less than between-individual variation, suggesting a unique individual microbial fingerprint. Principal Coordinates Analysis (PCO) suggests that there is a considerable separation between genders. These results suggest that there are specific microbial colonies characteristic of individuals.     

Picomolar FKBP inhibitors enabled by a single water-displacing methyl group in bicyclic [4.3.1] aza-amides

Methyl groups can have profound effects in drug discovery but the underlying mechanisms are diverse and incompletely understood. Here we report the stereospecific effect of a single, solvent-exposed methyl group in bicyclic [4.3.1] aza-amides, robustly leading to a 2 to 10-fold increase in binding affinity for FK506-binding proteins (FKBPs). This resulted in the most potent and efficient FKBP ligands known to date. By a combination of co-crystal structures, isothermal titration calorimetry (ITC), density-functional theory (DFT), and 3D reference interaction site model (3D-RISM) calculations we elucidated the origin of the observed affinity boost, which was purely entropically driven and relied on the displacement of a water molecule at the protein–ligand–bulk solvent interface. The best compounds potently occupied FKBPs in cells and enhanced bone morphogenic protein (BMP) signaling. Our results show how subtle manipulation of the solvent network can be used to design atom-efficient ligands for difficult, solvent-exposed binding pockets.

Enhancement by displacement. A single methyl group displaces a water molecule from the binding site of FKBPs, resulting in the most potent binders known, outperforming the natural products FK506 and rapamycin in biochemical and cellular assays.