Characterization of lanthanide-mediated DNA cleavage by intercalator-linked hydroxamic acids: comparison with transition systems

Abstract

Phenanthridine-linked hydroxamic acids with alkyl chain of variable length (n= 3, 4, 5, 6 and 7) have been newly synthesized. Their DNA cleavage activities have been investigated by Col E1 plasmid relaxation assay in the presence of transition(II)(ferrous and vanadyl) or lanthanide(III)(lutetium) metal ions. Linker length is extremely determinant for lutetium-mediated DNA cleavage. The increase in cleavage activity of the lutetium system with increasing pH suggests the involvement of metal-bound hydroxide as catalytically active species. Middle (samarium and europium) and late (thulium, ytterbium and lutetium) trivalent lanthanide systems are effective for DNA cleavage. For maximal DNA cleavage activity, the lutetium/hydroxamic acid ratio has been found to be 2 whereas that of the transition system has been found to be 1. We propose a hydrolytic mechanism in which two lanthanide ions are acting in concert for effective DNA cleavage.