Characterization of the Ni(III) intermediate in the reaction of (1,4,8,11-tetraazacyclotetradecane)nickel(II) perchlorate with KHSO5: Implications tothe mechanism of oxidative DNA modification

We report the detection and characterization of the Ni(III) intermediates g enerated by reaction of (1,4,8,11-tetraazacyclotetradecane)nickel(II) perch lorate with KHSO5. Four Ni(III) intermediates can be trapped or detected th rough variation in Cl- or KHSO5 concentrations. Upon oxidation of [Ni(cycla m)](2+) by 2.5 equiv of KHSO5, deprotonation of the cyclam ligand generates two red Ni(III) species with lambda (max) = 530 nm and g(perpendicular to) = 2.20 and g(parallel to) = 2.02 or g(perpendicular to) = 2.16 and g(paral lel to) = 2.01 for the axial 4-coordinate or 6-coordinate dichloride specie s, respectively. These forms decay to Ni(II) products via complex ligand ox idation mechanisms. The Ni(III) dichloride species can be reprotonated and subsequently binds to DNA via an outer-sphere interaction as evidenced by t he inverted sign of the CD signal near 400 nm. Cumulatively, the results in dicate that the Ni(III) center is coordinately saturated under excess chlor ide conditions but is still able to interact with DNA substrates. This sugg ests alternative mechanistic pathways for DNA modification by reaction of [ Ni(cyclam)](2+) with KHSO5 and possibly other Ni(II) complexes as well.