Cleavage of double-strand DNA by zinc complexes of dicationic 2,2′-dipyridyl derivatives

Abstract

Two highly charged zinc complexes, [Zn(L¹)₃](ClO₄)₈·4H₂O (1) and [Zn(L²)₂Br](ClO₄)₅·H₂O (2) (L1 = 5,5′-di(1-(triethylammonio)methyl)-2,2′-dipyridyl and L2 = 5,5′-di(1-(tributylammonio)methyl)-2,2′-dipyridyl) were synthesized and structurally characterized by crystallography. The zinc atom in 1 shows a distorted octahedral sphere. Variable-pH NMR studies on 1 demonstrated that the saturated six-coordinated [Zn(L¹)₃]⁸⁺ species can partially change into five-coordinated [Zn(L¹)₂(H₂O)]⁶⁺ species in aqueous solution. The zinc atom in 2 shows a distorted trigonal-bipyramidal sphere. The average distance of the coordinated Br atom to the cationic N atom in 2 is ca 5.9 Å, which is comparable to that of adjacent phosphodiesters in the DNA (ca. 6 Å). Both complexes exhibited high nuclease activitiestowards cleavage of supercoiled plasmid DNA with the activity being the maximum under physiological pH. The effective DNA cleavage may be attributed to the strong electrostatic interaction of the metal moiety and two positive pendants with phosphodiester groups of nucleic acid.