Krishna L. Bhat

Mutagenicity of aminoazobenzene dyes and related structures: a QSAR/QPAR investigation

Abstract Quantitative structure–activity/property–activity relationships (QSAR/QPARs) are developed that correlate the observed mutagenic activity of 43 aminoazobenzene derivatives with a variety of molecular descriptors calculated using quantum-chemical semiempirical methodology. Models based on multilinear regression techniques and artificial neural networks are presented that account for more than 80% of the variation in the reported relative mutagenicity of these compounds.

Thermodynamics of boroxine formation from the aliphatic boronic acid monomers R-B(OH)2 (R = H, H3C, H2N, HO, and F): a computational investigation.

Boroxines are the six-membered cyclotrimeric dehydration products of organoboronic acids, 3R–B(OH)2 → R3B3O3 + 3H2O, and in recent years have emerged as a useful class of organoboron molecules with applications in organic synthesis both as reagents and catalysts, as structural components in boronic-acid-derived pharmaceutical agents, and as anion acceptors and electrolyte additives for battery materials [Korich, A. L.; Iovine, P. M. Dalton Trans. 2010, 39, 1423−1431]. Second-order Møller–Plesset perturbation theory, in conjunction with the Dunning–Woon correlation-consistent cc-pVDZ, aug-cc-pVDZ, cc-pVTZ, and aug-cc-pVTZ basis sets, was used to investigate the structures and relative energies of the endo–exo, anti, and syn conformers of the aliphatic boronic acids R–B(OH)2 (R = H, H3C, H2N, HO, and F), as well as the thermodynamics of their boroxine formation; single-point calculations at the MP2/aug-cc-pVQZ, MP2/aug-cc-pV5Z, and CCSD(T)/aug-cc-pVTZ levels using the MP2/aug-cc-pVTZ optimized geometries were also performed in selected cases. The endo–exo conformer was generally lowest in energy in vacuo, as well as in PCM and CPCM models of aqueous and carbon tetrachloride media. The values of ΔH(298)(0) for boroxine formation via dehydration from the endo–exo conformers of these aliphatic boronic acids ranged from −2.9 for (H2N)3B3O3 to +12.2 kcal/mol for H3B3O3 at the MP2/aug-cc-pVTZ level in vacuo; for H3B3O3, the corresponding values in PCM/UFF implicit carbon tetrachloride and aqueous media were +11.2 and +9.8 kcal/mol, respectively. On the basis of our calculations, we recommend that ΔHf(298K) for boroxine listed in the JANAF compilation needs to be revised from −290.0 to approximately −277.0 kcal/mol.

Calculated values of the octanol-water partition coefficient and aqueous solubility for aminoazobenzene dyes and related structures

Abstract Results from calculations of the logarithm of the octanol–water partition coefficient, log P, and the aqueous solubility, S, for a wide range of arylamine dyes and related structures are presented. Since many arylamine dyes have functional groups that easily form ions, the logarithm of the apparent partition coefficient for dissociative systems, log D, has also been calculated as a function of pH for some of these compounds. Correlations of the observed biological behavior of various dyes with log P and S are discussed.

A Computational Characterization of Boron−Oxygen Multiple Bonding in HN═CH−CH═CH−NH−BO

Structures, relative energies, and bonding characteristics for various conformers of 3-imino-N-(oxoboryl)prop-1-en-1-amine, HN=CH-CH=CH-NH-BO, and the corresponding borocycle (-HN=CH-CH=CH-NH-B-)O are discussed using results from second-order Møller-Plesset (MP2) perturbation theory with the Dunning-Woon correlation-consistent cc-pVDZ, aug-cc-pVDZ, and cc-pVTZ basis sets. These MP2 results are compared to those from computationally efficient density functional theory (DFT) calculations using the LDA, PBE, TPSS, BLYP, B3LYP, BVP86, OLYP, O3LYP, and PBE1PBE functionals in conjunction with the economical Pople-type 6-311++G(d,p) basis set to evaluate the suitability of these DFT/6-311++G(d,p) levels for use with larger boron-containing systems. The effects of an aqueous environment were incorporated into the calculations using COSMO methodology. The calculated boron-oxygen bond lengths, orbital compositions, and bond orders in all the (acyclic) HN=CH-CH=CH-NH-BO conformers were consistent with the presence of a boron-oxygen triple bond, similar to that found in H-BO and H2N-BO. The (-HN=CH-CH=CH-NH-B-)O borocycle is predicted to be planar (C2v symmetry), and it is approximately 30 kcal/mol lower in energy than any of the (acyclic) HN=CH-CH=CH-NH-BO conformers; the boron-oxygen bond in this borocycle has significant double bond character, a bonding scheme for which there has been only one experimental structure reported in the literature (Vidovic, D. ; et al. J. Am. Chem. Soc. 2005, 127, 4566- 4569).

Mutagenicity of aminoazo dyes and their reductive-cleavage metabolites: a QSAR/QPAR investigation

Abstract Quantitative structure–activity/property–activity relationships are developed that correlate the observed mutagenic behavior of 62 aminoazo derivatives and 12 of their reductive cleavage products with a variety of molecular descriptors calculated using quantum-chemical semiempirical methodology. Multilinear regression techniques using 8 descriptors are shown to account for more than 70% of the variation in the relative mutagenic activity of these compounds. Approaches using artificial neural networks in conjunction with fuzzy logic can account for about 95% of this variation using 8 descriptors.

A computational study of the formation of a boron–oxygen–carbon linkage. The reaction of monohydroxy borane with methanol

Abstract Boronic acids are well known to form covalent linkages with compounds containing 1,2- or 1,3-diol moieties to form cyclic boronic esters. This unique ability of the boronic acid functional group has led to its use as the recognition entity in carbohydrate sensors. In the present computational study we discuss the formation of a prototypical boron–oxygen–carbon linkage by investigating the dehydration reaction: monohydroxy borane+methanol → borane methyl ether+water; density functional theory at the B3LYP/6-311++G** computational level is employed. Several alternative mechanisms for this reaction are considered and the influence of aprotic solvents and base catalysts are also discussed.

Monomethoxy-4-aminoazobenzenes: a computational study

Abstract The structural and electronic properties of the positional isomers of monomethoxy-4-aminoazobenzene (n-OMe-AAB) have been investigated using density functional theory with a basis set that includes polarization functions on all the atoms. These azo dyes are of interest because their carcinogenic activities depend dramatically on the position (n) of the methoxy group, e.g. 3-OMe-AAB is a potent hepatocarcinogen in the rat, whereas 2-OMe-AAB is a noncarcinogen. While it is generally believed that the various isomers of OMe-AAB require metabolic activation via N-hydroxylation prior to reaction with cellular macromolecules, we have shown that there are structural and electronic features present in these isomers that correlate with their carcinogenic behavior.

N-hydroxy-monomethoxy-4-aminoazobenzenes: a computational study

Abstract Structures and electronic properties of the N -hydroxy metabolites (N–OH–OMe–AAB) of the monomethoxy-4-aminoazobenzene dyes (OMe–AAB) have been calculated using density functional theory with a basis set that includes polarization functions on all the atoms. Positional isomers with the methoxy group ortho to the hydroxyamino group ( N –OH–3(5)-OMe–AAB) are found to be lower in energy than isomers with the methoxy group meta to the hydroxyamino group (N–OH–2(6)-OMe–AAB). The geometrical parameters of the phenyl rings for the corresponding isomers of OMe–AAB and N-OH–OMe–AAB are very similar. The length of the C–NHOH bond, however, is significantly longer than the length of the C–NH 2 bond. The energies of the frontier orbitals are more negative for each of the positional isomers of N–OH-OMe-AAB than for the corresponding isomer of OMe–AAB. In particular, the energy of the lowest unoccupied molecular orbital decreases a few kcal/mol for each isomer, suggesting that these N -hydroxy metabolites are slightly more electrophilic.

Thermodynamics and Kinetics of MTBE Degradation: A Density Functional Theory Study

Computational studies using density functional theory can help define which of a variety of reactions may be involved in the degradation of the fuel oxygenate methyl tert-butyl ether (MTBE). It is shown that hydrolysis of MTBE in the vapor phase or in neutral aqueous media, as well as its unimolecular decomposition, are not significant degradation mechanisms. The acid catalyzed hydrolysis of MTBE is a more feasible degradation pathway and is shown to proceed via tert-butyl carbonium ion formation. Hydrogen abstraction is shown to be the dominant first step in the degradation of MTBE initiated by hydroxyl radicals.

Synthesis of Chiral 3,4-Disubstituted Pyrroles from L-Amino Acids

A general methodology for the conversion of naturally occurring amino acids to 3,4-disubstituted pyrroles is described. A suitably protected amino acid (1) was first converted to the corresponding aldehyde (2). HornerEmmons olefination afforded a facile entry to the corresponding α,β-unsaturated ester (3). The construction of the pyrrole ring system was accomplished in a single step, using an intramolecular cyclization reaction with tosylmethyl isocyanide (TOSMIC).