Synthesis of glucopyranosyl Schiff base zinc(II) complexes capable of interacting with mononucleotides, and their DNA-cleavage activities

Abstract

New glucopyranosyl Schiff base zinc complexes, [Zn(GlcSal)(2) ] (1; GlcSalH=N-(2-deoxy-β-D-glucopyranos-2-yl-salicylaldimine) and [Zn(AcOGlcSal)(2) ] (2; AcOGlcSalH=N-(2-deoxy-β-D-1,3,4,6-tetraacetylglucopyranos-2-yl-salicylaldimine) were synthesized, and characterized by spectral and analytical methods. The interaction between the Zn complexes and mononucleotides was investigated by (1)H-NMR, (31)P-NMR and UV/VIS spectroscopies. Mononucleotides, cytidine 5'-monophosphate (CMP) and uridyl 5'-monophosphate (UMP), interacted with these complexes to form a 1:1 complex with 1 and a 1:2 complex with 2, depending on the presence of the OH group of glucopyranosyl substituents. The DNA-cleavage activities of 1 and 2 were studied using plasmid DNA (pBR322) in a medium of 5 mM Tris·HCl/50 mM NaCl buffer in the presence of H(2)O(2). The DNA-cleavage activity decreased in the order of 2>1>Zn(OAc)(2), indicating the significant promoting effect of the glucopyranosyl Schiff base ligand and the participation of the glucopyranosyl OH groups in the cleavage mechanism. The mechanism of the DNA cleavage by 1 and 2 was investigated by evaluation of the effect of a HO· radical scavenger and a singlet-oxygen ((1)O(2)) quencher under aerobic conditions. The former exhibited little effect, excluding the HO· radical as an active species and supporting the hydrolysis mechanism for the main process of the DNA cleavage. The latter quencher somewhat hindered the cleavage, indicating the partial participation of a (1)O(2) as a competitive active species in the present system.