Synthetic analogues for oxovanadium(IV) - Glutathione interaction: An EPR, synthetic and structural study of oxovanadium(IV) compounds with sulfhydryl-containing pseudopeptides and dipeptides

Abstract

Valuable analogues of the VIVO2+ - glutathione complex have been synthesized and characterized. The reaction of [VIVO(CH3COO)2(phen)] (phen = 1,10-phenanthroline) with the sulfhydryl-containing pseudopeptides (scp) N-(2-mercaptopropionyl)cysteine (H4m2pc), and N-(3-mercaptopropionyl)cysteine (H4m3pc) in the presence of triethylamine gives the oxovanadium(IV) compounds [(Et3NH)2][VO(m2pc)] (1) and [(Et3NH)2][VO(m3pc)] (2), while reaction of [VOCl2(phen)] with the scp N-(2-mercaptopropionyl)glycine (H3mpg) and the dipeptides glycylglycine (H2glygly) and glycyl-L-alanine (H2glyala) in the presence of triethylamine results in the formation of the compounds [Et3NH]-[VO(mpg)(phen)] (3), [VO(glygly)-(phen)]·2CH3OH (4·2CH3OH), and [VO(glyala)(phen)]·CH3OH (5·CH3OH). Complex [VOCl2(phen)(CH3OH)] (7) was prepared by the reaction of [VOCl2(thf)2] with phen in a methanolic solution. The X-ray structure of 3 shows that the vanadium(IV) atom is ligated to a tridentate mpg3- ligand at the Sthiolato, Npeptide and Ocarboxylato atoms. The X-ray structure of 7 is also reported. The optical, infrared, magnetic, electron paramagnetic resonance, and electrochemical properties of compounds 1-5· CH3OH and 7 were studied. Combination of the correlation plots of the EPR parameters gz versus Az, or the groundstate orbital population (β*)2 versus Az, together with the additivity relationship, Az,calcd = ΣniAzi/4, were shown to provide a powerful tool for probing the equatorial donor atoms in an oxovanadium(IV) compound and consequently in biomolecules. Thus, these methods provide valuable evidence for the assignment of the equatorial donor atoms for the VIVO2+ center of the VIVO2+ - glutathione system at various pH values. Model NMR studies (interaction of vanadium(V) with H3mpg) showed that there is a possibility of vanadium(V) ligation to glutathione. The contribution of a deprotonated peptide(amide) nitrogen to Az is not a fixed quantity (it varies from 29 to 43 × 10-4 cm-1), but is influenced by the presence of the three other donor atoms in the equatorial plane and, in particular, their charge.