Synthesis, Characterization, Stereochemistry and Antimicrobial Evaluation of N-Acyltetrahydrobenzodiazepin-2-ones

A few N5-substituted (1) and N1,N5-disubstituted tetrahydro-1,5-benzodiazepin-2-ones (2-8) viz. N5-chloroacetyl-, N5-formyl-, N5-dichloro-acetyl-, N1,N5-diethoxycarbonyl-, N1,N5-bischloroacetyl-, N5-piperazinoacetyl- and N5-morpholinoacetyltetrahydro-1,5-benzodiazepin-2-ones have been synthesized. The characterization and conformational analysis of these compounds 2-8 have been carried out using IR and 1H, 13C, DEPT & 2D (COSY & HSQC) NMR spectral techniques. The coupling constants for compounds 3-6 were determined by irradiating the C4-methyl doublet. The appearance of major and minor conformers has been found in the case of benzodiazepin-2-ones (3 and 6) and the spectral data confirm the equilibrium due to ring inversion over the N-C=O rotation. The spectral data and the extracted coupling constant values revealed that the substituted tetrahydro-1,5-benzodiazepin-2-ones (2-8) prefer to adopt boat conformation. The antimicrobial activity of compounds 1-8 has also been evaluated.

Molecular dynamics simulations of hexopyranose ring distortion in different force fields

The four classical, biomolecular force fields designed to study hexopyranose-based carbohydrates (GROMOS 56a6CARBO/56a6CARBO_R, GROMOS 53a6GLYC, CHARMM and GLYCAM06) have been tested in the context of ring-inversion properties. These properties were evaluated for both unfunctionalized monomers of all hexopyranoses of the d series and for residues in a chain composed of uniform units connected by α(1→4) and β(1→4) glycosidic linkages. The results indicate that the tested force fields differ in their predictions of the ring-inversion properties of both monomers and residues in a chain. The comparison with the available experimental data and with the semi-empirical Angyal scheme reveals that, at the level of monomers, GROMOS 56a6CARBO, GROMOS 53a6GLYC and CHARMM correctly reproduce the ring-inversion free energies. However, due to the lack of analogous reference data we cannot state which force field is more or less accurate in the context of ring distortion of residues in a chain. Therefore, the use of ab initio potentials is recommended in the prospective, quantitative studies on the related subject.

Pyranose ring conformations in mono- and oligosaccharides: a combined MD and DFT approach

A two-step computational protocol is proposed to efficiently study the conformational properties of hexopyranoses with a special emphasis on their ring-inversion-properties. By applying it, the errors resulting from overestimating the contribution of the hydrogen bond-rich, low-energy structures that are not abundant in aqueous solutions are avoided.