DNA AND RNA MODIFICATION PROMOTED BY [CO(H2O)(6)]CL-2 AND KHSO5 - GUANINE SELECTIVITY, TEMPERATURE-DEPENDENCE, AND MECHANISM

Reaction of a single-stranded oligodeoxynucleotide or a 17-base hairpi n-forming oligodeoxynucleotide with CoCl2 and KHSO5 produced guanine-s pecific cleavage after piperidine treatment. The observed reactivity i s shown to be nearly twice that obtained for NiCR icyclo[11.3.1]heptad eca-1(17),2,11,13,15-pentaene) under equivalent conditions, although N iCR displays a slightly higher degree of selectivity for unpaired guan ine residues. Cobalt-induced DNA modification was catalytic with respe ct to the,metal complex and was observed at temperatures up to 80 degr ees C, conditions under which NiCR was ineffective. Mechanistic studie s of the cobalt-mediated reaction suggest that SO4.- is responsible fo r guanine oxidation. Reaction with tRNA(Phe) induced aniline . HOAc-la bile (pH 4.5) lesions also at accessible guanine sites. The high react ivities of G20 acid G34 are consistent with attack of SO4.- on the rr face of the guanine heterocycle as opposed to recognition of G N7 as p roposed for NiCR. CoCl2 should become an extremely attractive probe of nucleic acid structure since it induces base-specific and conformatio n-specific cleavage of DNA under a much wider variety of experimental conditions than NiCR, acts with a different mode of guanine selectivit y than do nickel complexes, and is commercially available.