Double-strand DNA hydrolysis by dilanthanide complexes

Although there has been progress in developing artificial hydrolytic DNA cleaving agents, none of these has been shown to carry out the double-strand hydrolysis of DNA. We demonstrate that La(III) or Ce(IV) combined with the ligand 1,3-diamino-2-hydroxypropane-N,N,N',N'-tetraacetate (HPTA) in a 2:1 ratio can efficiently cleave supercoiled plasmid DNA at 55 degrees C within a 3-h period. Analysis of end-labeled restriction fragments cleaved by these complexes reveals 3'- and 5'-ends consistent with a hydrolytic mechanism. Unlike for other polydentate carboxylate complexes, plasmid DNA cleavage by La-2(HPTA) or Ce-2(HPTA) affords a significant amount of linear DNA with a considerable fraction of the supercoiled form still remaining. This result implies that La-2(HPTA) and Ce-2(HPTA) can carry out double-strand cleavage of plasmid DNA. La-2(HPTA) and Ce-2(HPTA) represent the first metal complexes demonstrated to be capable of double-strand hydrolytic cleavage of plasmid DNA.