Structure, characterization and kinetics of nickel complexes and reactions with biomolecules

The macrocyclic square planar nickel complex, [Ni IICR]2+, has been shown to be a useful DNA or RNA structure probe due to its highly site- and conformation specific ability to induce cleavage on exposed guanine residues via the formation of a direct guanine N7-NiIII bond. Since the postulated intermediate [Ni IIICR]3+ is unstable, the detailed mechanism is unknown. In this study, the nature of the interaction of NiCR2+ and its oxidized products with biomolecules was investigated.; A study of the conversion of [NiIICR]2+ between a diamagnetic square planar structure and a paramagnetic tetragonal structure in aqueous solution has shown that the conversion is affected by the identity and the concentration of the counter anion. Of the anions studied, it is clear that Br−, ClO₄−, and CF₃SO₃− have a higher ability to promote the conversion to the square planar form for [NiCR]2+ than Cl− or CF₃COO−.; The oxidation reaction of [NiCR]2+ with either KHSO ₅ or Na₂S₂O₈ in a molar ratio of 1/1 resulted in the same stable complex [Ni(CR-2H)]2+. A single crystal x-ray diffraction study gave the structure of Ni(CR-2H)(ClO₄ )₂. In addition, kinetic studies revealed the oxidation reaction to be first order.; The six protons on the two methyl groups of the macrocyclic ligand were also found to be sufficiently labile to exhibit hydrogen/deuterium exchange. The [Ni(CR-2H)]2+ displays a higher acidity than [NiCR] 2+ by H/D exchange. This observation supports the conjecture that there is an enhanced dπ-pπ* back-bonding effect associated with the presence of the additional imine formed in [Ni(CR-2H)]2+.; The [NI(CR-2H)]2+ species with KHSO₅ also displays an oxidation ability similar to [NiCR]2+ with KHSO₅ in the reaction with a 17 base pair synthetic oligonucleotide. This implies that [Ni(CR-2H)]2+ is not just an oxidation product of [NiCR] 2+, but may also play an important role in the reaction with guanine residues in oligonucleotides.; The reactions of [NiCR]2+ or [Ni(CR-2H)]2+ with linoleic acid under a high concentration of Ni complexes (3.21 × 10−3 M, 200 fold over linoleic acid) resulted in the unexpected reduced nickel complexes, (Ni0(CR-4H)-H+ )− - m/z 311.1 and (Ni0(CR-2H)-H +)− - m/z 313.1, instead of the hydroperoxide product (HpODE-H+)− - m/z 311.2.