DNA and RNA Modification Promoted by [Co(H₂O)₆]Cl₂ and KHSO₅: Guanine Selectivity, Temperature Dependence, and Mechanism

Abstract

Reaction of a single-stranded oligodeoxynucleotide or a 17-base hairpin-forming oligodeoxynucleotide with CoCl2 and KHSO5 produced guanine-specific cleavage after piperidine treatment. The observed reactivity is shown to be nearly twice that obtained for NiCR (CR = 2,12-dimethyl-3,7,11,17-tetraazabicyclo[11.3.1]heptadeca-1(17),2,11,13,15-pentaene) under equivalent conditions, although NiCR displays a slightly higher degree of selectivity for unpaired guanine residues. Cobalt-induced DNA modification was catalytic with respect to the metal complex and was observed at temperatures up to 80 °C, conditions under which NiCR was ineffective. Mechanistic studies of the cobalt-mediated reaction suggest that SO4•- is responsible for guanine oxidation. Reaction with tRNAPhe induced aniline·HOAc-labile (pH 4.5) lesions also at accessible guanine sites. The high reactivities of G20 and G34 are consistent with attack of SO4•- on the π face of the guanine heterocycle as opposed to recognition of G N7 as proposed for NiCR. CoCl2 should become an extremely attractive probe of nucleic acid structure since it induces base-specific and conformation-specific cleavage of DNA under a much wider variety of experimental conditions than NiCR, acts with a different mode of guanine selectivity than do nickel complexes, and is commercially available.