Distributed and multicore QuBiLS-MIDAS software v2.0: Computing chiral,fuzzy, weighted and truncated geometrical molecular descriptors based on tensor algebra

Advances to the distributed, multi-core and fully cross-platform QuBiLS-MIDAS software v2.0 ( http://tomocomd.com/qubils-midas ) are reported in this article since the v1.0 release. The QuBiLS-MIDAS software is the only one that computes atom-pair and alignment-free geometrical MDs (3D-MDs) from several distance metrics other than the Euclidean distance, as well as alignment-free 3D-MDs that codify structural information regarding the relations among three and four atoms of a molecule. The most recent features added to the QuBiLS-MIDAS software v2.0 are related (a) to the calculation of atomic weightings from indices based on the vertex-degree invariant (e.g., Alikhanidi index); (b) to consider central chirality during the molecular encoding; (c) to use measures based on clustering methods and statistical functions to codify structural information among more than two atoms; (d) to the use of a novel method based on fuzzy membership functions to spherically truncate inter-atomic relations; and (e) to the use of weighted and fuzzy aggregation operators to compute global 3D-MDs according to the importance and/or interrelation of the atoms of a molecule during the molecular encoding. Moreover, a novel module to compute QuBiLS-MIDAS 3D-MDs from their headings was also developed. This module can be used either by the graphical user interface or by means of the software library. By using the library, both the predictive models built with the QuBiLS-MIDAS 3D-MDs and the QuBiLS-MIDAS 3D-MDs calculation can be embedded in other tools. A set of predefined QuBiLS-MIDAS 3D-MDs with high information content and low redundancy on a set comprised of 20,469 compounds is also provided to be employed in further cheminformatics tasks. This set of predefined 3D-MDs evidenced better performance than all the universe of Dragon (v5.5) and PaDEL 0D-to-3D MDs in variability studies, whereas a linear independence study proved that these QuBiLS-MIDAS 3D-MDs codify chemical information orthogonal to the Dragon 0D-to-3D MDs. This set of predefined 3D-MDs would be periodically updated as long as new results be achieved. In general, this report highlights our continued efforts to provide a better tool for a most suitable characterization of compounds, and in this way, to contribute to obtaining better outcomes in future applications.     

Experimental Determination of the Electronic Polarizability of Quinoline and Isoquinoline in Solution by Three New Strategies

The values of electronic polarizability of quinoline and isoquinoline in extremely diluted liquid solution are reported in this paper. These were obtained by means of three new strategies based on UV-visible-NIR spectroscopy, the Kramers-Krönig relations, high precision densitometry and high exactitude refractometry, which are called here Arakawa’s Approximation (AA), Optical Substractive Approximation (OSA) and Optical Differential Approximation (ODA). In general the static electronic polarizability values of solute molecules obtained by ODA and OSA are in excellent agreement with the reported theoretical values at the Density Functional Theory (DFT) level and the Atom monopole-dipole model, but strong discrepancies were observed with the experimental values previously reported for quinoline and isoquinoline using refractometric and electro-optic methods. These differences were interpreted and analyzed in terms of dielectric intermolecular forces, resonant and pre-resonant effects. The AA method is shown to fail in predicting the polarizability of the quinoline and isoquinoline molecules.     

Machine learning approach to discovery of small molecules with potential inhibitory action against vasoactive metalloproteases

Molecular Diversity - With the advancement of combinatorial chemistry and big data, drug repositioning has boomed. In this sense, machine learning and artificial intelligence techniques offer a...     

Experimental and Theoretical Determination of the Limiting Partial Molar Volume of Indole in CCl<Subscript>4</Subscript>, Tetrahydrofuran and Acetonitrile at 293.15 K: A Comparative Study with Benzimidazole and Benzothiophene

The partial molar volumes of indole(Ind) at infinite dilution (V₂^￥V_{2}^{\infty}) in carbon tetrachloride (CCl₄), acetonitrile (ACN) and tetrahydrofuran (THF) as solvents, were estimated from densitometry measurements at 293.15 K. The results indicate that $V_{2}^{\infty}\mbox{(ACN)}>V_{2}^{\infty}\mbox{(CCl$V_{2}^{\infty}\mbox{(ACN)}>V_{2}^{\infty}\mbox{(CCl $\approx V_{2}^{\infty}\mbox{(THF)}$\approx V_{2}^{\infty}\mbox{(THF)}. The values determined in this study are close to the values calculated from reported density for Ind in the solid state. In order to make a comparison the partial molecular volume of benzimidazole (Bim) and benzothiophene (BT) in solvents with appropriate solubility were measured too, and the results have revealed that $V_{2}^{\infty}\mbox{(BT)}>V_{2}^{\infty}\mbox{(Ind)}$V_{2}^{\infty}\mbox{(BT)}>V_{2}^{\infty}\mbox{(Ind)} in CCl₄ and $V_{2}^{\infty}\mbox{(Ind)}>V_{2}^{\infty}\mbox{(Bim)}$V_{2}^{\infty}\mbox{(Ind)}>V_{2}^{\infty}\mbox{(Bim)} in THF. In this work the role of solvent reorganization around to solute cavity, and specific and nonspecific interactions on the volumetric behavior of these molecules in solution are discussed using the Terasawa-Itsuki-Arakawa model, the Lee-Graziano model, molar volumes of solutes calculated at the DFT-B3LYP/cc-pVTZ and aug-cc-pVTZ level in the gas phase and considering solvent presence with the Onsager’s reaction field, and the van der Waals volume. This analysis suggests that the molecular volumes of solutes are overestimated by the quantum methods employed in this work and that the volumetric contribution from the van der Waals components to the limiting partial molecular volumes of solutes is important, with the exception of Ind in CCl₄ where the solvent reorganization is the dominant factor.