Biocatalyst-mediated selective acylation and deacylation chemistry on the secondary hydroxyl/amine groups of nucleosides.

Nucleosides play a pivotal role in biological systems and therefore have attracted a lot of interest as chemotherapeutic agents in drug discovery. Over the years biocatalysts have emerged as a sustainable alternative to conventional synthetic catalysts. As a nature's catalyst, they exhibit excellent selectivity, remarkable tolerance, and help in carrying out eco-friendly benign processes. The use of a biocatalyst as a regio- and enantioselective catalyst is particularly relevant in the transformations of nucleosides and their analogs because of the presence of multiple chiral centres. Herein, we discuss the recent advances in the Pseudomonas Cepacia Lipase mediated selective acylation and deacylation reactions of the secondary hydroxyl and amino groups of nucleosides and their analogs.

Antimalarial evaluation of copper(II) nanohybrid solids: inhibition of plasmepsin II, a hemoglobin-degrading malarial aspartic protease from Plasmodium falciparum.

A new class of copper(II) nanohybrid solids, LCu(CH(3)COO)(2) and LCuCl(2), have been synthesized and characterized by transmission electron microscopy, dynamic light scattering, and IR spectroscopy, and have been found to be capped by a bis(benzimidazole) diamide ligand (L). The particle sizes of these nanohybrid solids were found to be in the ranges 5-10 and 60-70 nm, respectively. These nanohybrid solids were evaluated for their in vitro antimalarial activity against a chloroquine-sensitive isolate of Plasmodium falciparum (MRC 2). The interactions between these nanohybrid solids and plasmepsin II (an aspartic protease and a plausible novel target for antimalarial drug development), which is believed to be essential for hemoglobin degradation by the parasite, have been assayed by UV-vis spectroscopy and inhibition kinetics using Lineweaver-Burk plots. Our results suggest that these two compounds have antimalarial activities, and the IC(50) values (0.025-0.032 microg/ml) are similar to the IC(50) value of the standard drug chloroquine used in the bioassay. Lineweaver-Burk plots for inhibition of plasmepsin II by LCu(CH(3)COO)(2) and LCuCl(2) show that the inhibition is competitive with respect to the substrate. The inhibition constants of LCu(CH(3)COO)(2) and LCuCl(2) were found to be 10 and 13 microM, respectively. The IC(50) values for inhibition of plasmepsin II by LCu(CH(3)COO)(2) and LCuCl(2) were found to be 14 and 17 microM, respectively. Copper(II) metal capped by a benzimidazole group, which resembles the histidine group of copper proteins (galactose oxidase, beta-hydroxylase), could provide a suitable anchoring site on the nanosurface and thus could be useful for inhibition of target enzymes via binding to the S1/S3 pocket of the enzyme hydrophobically. Both copper(II) nanohybrid solids were found to be nontoxic against human hepatocellular carcinoma cells and were highly selective for plasmepsin II versus human cathepsin D. The pivotal mechanism of antimalarial activity of these compounds via plasmepsin II inhibition in the P. falciparum malaria parasite is demonstrated.

Synthesis and spectral studies of copper complexes using a N-octylated bis benzimidazole diamide ligand.

Monomeric Cu(II) and Cu(I) complexes bound to a tetradentate bis-benzimidazole diamide ligand N,N'-bis(N-octyl benzimidazolyl-2yl)(methyl)pentane diamide (O-GBGA) have been isolated and characterized. X-Band EPR spectra of the copper(II) complexes in CH2Cl2 were recorded in a frozen solution as solvent at liquid nitrogen temperature. Solution spectra typically indicate a d(x2-y2) ground state (g||>g⊥>2.0023) and show less than four nuclear hyperfine lines with broadening of g⊥ line in some cases, thus indicating distorted tetragonal geometry. One of the copper(II) complexes shows a five line N-SHF structure (16±1G) implying the binding of imine nitrogen of the benzimidazole to copper ion. α2 ranges from 0.57-0.97 indicating considerable amount of covalent character in Cu-L bond. Anodic shifts in E1/2 values indicate the retention of anion in the coordination sphere of Cu(II), E1/2 values becoming anodic in the order C6H5COO-

Synthesis, spectral and catalytic activity of some manganese(II) bis-benzimidazole diamide complexes.

Four Mn(II) complexes bound to a neutral bis-benzimidazole diamide ligand N,N'-bis(2-methyl benzimidazolyl 2,2'-oxy-diethanamide) (GBOA) have been synthesized and characterized. Anionic ligand associated with the complexes varies as Cl- CH3COO-, SCN- and ClO4-. X-ray structure of one of the complexes [Mn(GBOA)2(H2O)2]Cl(2)·4H2O was solved and shows that the Mn(II) ion is hexacoordinate. Two equatorial positions are occupied by benzimidazole imine nitrogen atoms while the other two sites are occupied by amide carbonyl oxygens. The imine nitrogen and carbonyl oxygens are bound to Mn(II) by different arms of the two ligands while axial sites are occupied by two water molecules. Two Cl- anions are outside the coordination sphere and form an extensive 3D H-bonded network. Axially distorted octahedral geometry is confirmed for all the four complexes by low temperature EPR spectroscopy. Distortion parameter D was found to be similar for [Mn(GBOA)2(H2O)2]Cl(2)·4H2O and [Mn(GBOA)2(H2O)2]·(CH3COO)2·H2O. Cyclic voltammograms have been obtained for all the four complexes and E(1/2) values are dependent on the anionic ligand being in the coordination sphere or outside. [Mn(GBOA)2(H2O)2]Cl(2)·4H2O and [Mn(GBOA)2(H2O)2]·(CH3COO)2·H2O carry out the selective oxidation of N-benzyldimethylamine, and 1-methyl-pyrollidine to their respective carbonyl products with catalytic efficiency of 35-50%.