From Zn to Mn: the study of novel manganese-binding groups in the search for new drugs against tuberculosis.

In most eubacteria, apicomplexans, and most plants, including the causal agents for diseases such as malaria, leprosy, and tuberculosis, the methylerythritol phosphate pathway is the route for the biosynthesis of the C(5) precursors to the essential isoprenoid class of compounds. Owing to their absence in humans, the enzymes of the methylerythritol phosphate pathway have become attractive targets for drug discovery. This work investigates a new class of inhibitors against the second enzyme of the pathway, 1-deoxy-D-xylulose 5-phosphate reductoisomerase. Inhibition of this enzyme may involve the chelation of a crucial active site Mn ion, and the metal-chelating moieties studied here have previously been shown to be successful in application to the zinc-dependent metalloproteinases. Quantum mechanics and docking calculations presented in this work suggest the transferability of these metal-chelating compounds to Mn-containing 1-deoxy-D-xylulose 5-phosphate reductoisomerase enzyme, as a promising starting point to the development of potent inhibitors.

Synthesis, characterization and antimicrobial activity of Fe(II), Zn(II), Cd(II) and Hg(II) complexes with 2,6-bis(benzimidazol-2-yl) pyridine ligand.

2,6-Bis(benzimidazol-2-yl)pyridine (L) ligand and complexes [M(L)Cl(2)] and [Fe(L)(2)](ClO(4))(2) (M=Zn, Cd, Hg) have been synthesized. The geometries of the [M(L)Cl(2)] complexes were derived from theoretical calculation in DGauss/DFT level (DZVP basis set) on CACHE. The central M(II) ion is penta-coordinated and surrounded by N(3)Cl(2) environment, adopting a distorted trigonal bipyramidal geometry. The ligand is tridentate, via three nitrogen atoms to metal centre and two chloride ions lie on each side of the distorted benzimidazole ring. In the [Fe(L)(2)](ClO(4))(2) complex, the central Fe(II) ion is surrounded by two (3N) units, adopting a octahedral geometry. The elemental analysis, molecular conductivity, FT-Raman, FT-IR (mid-, far-IR), (1)H, and (13)C NMR were reported. The antimicrobial activities of the free ligand, its hydrochloride salt, and the complexes were evaluated using the disk diffusion method in dimethyl sulfoxide (DMSO) as well as the minimal inhibitory concentration (MIC) dilution method, against 10 bacteria and the results compared with that for gentamycin. Antifungal activities were reported for Candida albicans, Kluyveromyces fragilis, Rhodotorula rubra, Debaryomyces hansenii, Hanseniaspora guilliermondii, and the results were referenced against nystatin, ketaconazole, and clotrimazole antifungal agents. In most cases, the compounds tested showed broad-spectrum (Gram positive and Gram negative bacteria) activities that were either more effective than or as potent as the references. The binding of two most biologically effective compounds of zinc and mercury to calf thymus DNA has also been investigated by absorption spectra.

Solvation of dried dentin matrix by water and other polar solvents.

PURPOSE: To develop a simple method for measuring the degree of solvation of dried, demineralized dentin matrix by water and other polar solvents. The null hypothesis was that there are no differences in expansion forces produced by different polar solvents. MATERIALS AND METHODS: Midcoronal dentin discs were prepared from extracted, unerupted human third molars. The discs were cut into square specimens with surface areas of 2 x 2, 3 x 3 and 4 x 4 mm and thicknesses of 0.5, 1.0 and 1.5 mm. After demineralization in 0.5 M EDTA (pH 7), the dimensions of the specimens were measured both wet and dry. Dry specimens were held between two parallel steel plates connected to a 50 N load cell which measured the solvation force when water or other polar solvents were added. After measuring the expansion force induced by water, the specimens were fixed in glutaraldehyde and the trials repeated. On additional specimens, repeated measures of expansion forces were obtained using water, methanol, ethanol, n-propanol, n-butanol, ethylene glycol, formamide, hydroxyethylmethacrylate, N,N-dimethyl formamide and acetone in unfixed specimens. RESULTS: Water produced hydration forces as high as 204 g before, and 428 g after glutaraldehyde treatment. The hydration force correlated better with specimen thickness than with surface area. Water solvated the matrix faster than methanol > ethanol > formamide > ethylene glycol. Hydroxyethylmethacrylate, N,N-dimethyl formamide and acetone were unable to solvate the dried matrix. Regression analysis of solvation force vs. Hansen's solubility parameters for dispersive, polar and hydrogen bonding forces demonstrated that solvation force correlations were highest with hydrogen bonding solubility parameters. Measurements of solvation forces provides a simple method for determining solvent-collagen matrix interactions.