Hwang Jung H, Larson Rhonda K, Abu-Omar Mahdi M
Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1569, USA.
Inorg Chem. 2003 Dec 1;42(24):7967-77. doi: 10.1021/ic0350180.
Bisperoxovanadium(V) compounds with bidentate ligands have shown tumor growth inhibition by cleaving DNA. The kinetics and mechanisms of ligand substitution reactions of two bisperoxovanadium(V) compounds VO(O(2))(2)(bpy) (bpVbpy) and VO(O(2))(2)(phen) (bpVphen) with entering ligands picolinic acid (pic) and dipicolinic acid (dipic) at physiological pH are reported, and its relevance to their DNA-cleavage activities are discussed. The products of the ligand substitution reactions with pic and dipic are the monoperoxo complexes VO(O(2))(pic)(2) and VO(O(2))(dipic)(H(2)O), respectively. (51)V NMR experiments indicate that bpVphen is substantially more inert in aqueous solution than bpVbpy. As a result, bpVbpy is more prone to ligand substitution and subsequent conversion to monoperoxo species. The rate of reaction for bpVbpy was faster than that of bpVphen by an order of magnitude, indicating that the ancillary ligand plays an important role in ligand substitution reactions. The ligand substitution reactions of bpVbpy feature first-order dependence on both pic and dipic whereas the substitution kinetics of bpVphen feature saturation behavior with dipic. The substitution reactions of both bpVbpy and bpVphen with pic showed first-order dependence on [H(+)] whereas no acid dependence was observed for the reactions with dipic. Hydrogen peroxide was determined to be a competitive inhibitor with respect to dipic. The ligand substitution reaction mechanisms and the rate laws consistent with these results are presented. The substitution reactions with pic and dipic proceed through different mechanisms; the substitution reactions with dipic proceed via solvolysis as the first step in the mechanisms whereas the reactions with pic bypass solvolysis to go through a mixed ligand monoperoxo vanadium intermediate.
具有双齿配体的双过氧钒（V）化合物已显示出通过切割DNA来抑制肿瘤生长。本文报道了两种双过氧钒（V）化合物[VO(O₂)₂(bpy)]⁻（bpVbpy）和[VO(O₂)₂(phen)]⁻（bpVphen）在生理pH值下与进入配体吡啶甲酸（pic）和二吡啶甲酸（dipic）的配体取代反应的动力学和机制，并讨论了其与它们的DNA切割活性的相关性。与pic和dipic发生配体取代反应的产物分别是单过氧配合物[VO(O₂)(pic)₂]⁻和[VO(O₂)(dipic)(H₂O)]⁻。⁵¹V NMR实验表明，bpVphen在水溶液中的惰性比bpVbpy大得多。因此，bpVbpy更容易发生配体取代并随后转化为单过氧物种。bpVbpy的反应速率比bpVphen快一个数量级，表明辅助配体在配体取代反应中起重要作用。bpVbpy的配体取代反应对[pic]ₜ和[dipic]ₜ均表现出一级依赖性，而bpVphen的取代动力学对dipic表现出饱和行为。bpVbpy和bpVphen与pic的取代反应对[H⁺]均表现出一级依赖性，而与dipic的反应未观察到酸依赖性。已确定过氧化氢是dipic的竞争性抑制剂。本文提出了与这些结果一致的配体取代反应机制和速率定律。与pic和dipic的取代反应通过不同的机制进行；与dipic的取代反应在机制的第一步通过溶剂解进行，而与pic的反应绕过溶剂解，通过混合配体单过氧钒中间体进行。
