Nickel-catalyzed oxidations: from hydrocarbons to DNA

Nickel(II) complexes of tetradentate ligands such as cyclam and salen are catalysts for olefin epoxidation using PhIO and NaOCl, respectively. In order to understand the lack of enantioselectivity observed with chiral cyclam and salen complexes, studies of DNA and RNA oxidation were carried out in which evidence for diffusible oxidants might be found. A variety of square-planar, tetradentate nickel(II) complexes were observed to mediate guanine-specific modification in the presence of KHSO5 or magnesium monoperphthalate. In particular, the cationic complex, [(2,12-dimethyl-3,7,11,17-tetraazabicyclo [11.3.1]heptadeca-1(17),2,11,13,15-pentaenato)nickel]2+, [NiCR]2+, has been studied as a probe of nucleic acid folding. The extent of guanine reaction depends upon the exposure of N7, a good transition metal binding site, thus implicating nickel-guanine binding during DNA oxidation. If this is the case, related systems should be able to confer enantioselectivity during the use of chiral nickel complexes and achiral substrates for oxidation. Mechanistic studies, including radical quenching and DNA enantioselectivity, are described and their mechanistic implications discussed.