Morlok Melissa M, Janak Kevin E, Zhu Guang, Quarless Duncan A, Parkin Gerard
Department of Chemistry, Columbia University, New York, New York 10027, USA.
J Am Chem Soc. 2005 Oct 12;127(40):14039-50. doi: 10.1021/ja0536670.
The zinc thiolate complex [Tm(Ph)]ZnSCH2C(O)N(H)Ph, which features a tetrahedral [ZnS4] motif analogous to that of the Ada DNA repair protein, may be obtained by the reaction of Zn(NO3)2 with [Tm(Ph)]Li and Li[SCH2C(O)N(H)Ph] ([Tm(Ph)] = tris(2-mercapto-1-phenylimidazolyl)hydroborato ligand). Structural characterization of [Tm(Ph)]ZnSCH2C(O)N(H)Ph by X-ray diffraction demonstrates that the molecule exhibits an intramolecular N-H...S hydrogen bond between the amide N-H group and thiolate sulfur atom, a structure that is reproduced by density functional theory (DFT) calculations. The thiolate ligand of [Tm(Ph)]ZnSCH2C(O)N(H)Ph is subject to alkylation, a reaction that is analogous to the function of the Ada DNA repair protein. Specifically, [Tm(Ph)]ZnSCH2C(O)N(H)Ph reacts with MeI to yield PhN(H)C(O)CH2SMe and [Tm(Ph)]ZnI, a reaction which is characterized by second-order kinetics that is consistent with either (i) an associative mechanism or (ii) a stepwise dissociative mechanism in which the alkylation step is rate determining. Although the kinetics studies are incapable of distinguishing between these possibilities, a small normal kinetic isotope effect of kH/kD = 1.16(1) at 0 degrees C for the reaction of [Tm(Ph)]ZnSCH2C(O)N(H*)Ph (H* = H, D) with MeI is suggestive of a dissociative mechanism on the basis of DFT calculations. In particular, DFT calculations demonstrate that a normal kinetic isotope effect requires thiolate dissociation because it results in the formation of [PhN(H)C(O)CH2S]- which, as an anion, exhibits a stronger N-H...S hydrogen bonding interaction than that in [Tm(Ph)]ZnSCH2C(O)N(H)Ph. Correspondingly, mechanisms that involve direct alkylation of coordinated thiolate are predicted to be characterized by kH/kD < or = 1 because the reaction involves a reduction of the negative charge on sulfur and hence a weakening of the N-H...S hydrogen bonding interaction.
硫醇锌配合物[Tm(Ph)]ZnSCH2C(O)N(H)Ph具有类似于Ada DNA修复蛋白的四面体[ZnS4]结构单元，它可通过Zn(NO3)2与[Tm(Ph)]Li和Li[SCH2C(O)N(H)Ph]（[Tm(Ph)] = 三(2-巯基-1-苯基咪唑基)硼氢化配体）反应得到。通过X射线衍射对[Tm(Ph)]ZnSCH2C(O)N(H)Ph进行结构表征表明，该分子在酰胺N-H基团和硫醇盐硫原子之间存在分子内N-H...S氢键，密度泛函理论(DFT)计算重现了这种结构。[Tm(Ph)]ZnSCH2C(O)N(H)Ph的硫醇盐配体可发生烷基化反应，这一反应类似于Ada DNA修复蛋白的功能。具体而言，[Tm(Ph)]ZnSCH2C(O)N(H)Ph与MeI反应生成PhN(H)C(O)CH2SMe和[Tm(Ph)]ZnI，该反应的特征是二级动力学，这与以下两种情况一致：(i) 缔合机理；(ii) 分步解离机理，其中烷基化步骤是速率决定步骤。尽管动力学研究无法区分这些可能性，但在0℃下，[Tm(Ph)]ZnSCH2C(O)N(H*)Ph（H* = H, D）与MeI反应的kH/kD = 1.16(1)的小正常动力学同位素效应，基于DFT计算表明是解离机理。特别是，DFT计算表明正常动力学同位素效应需要硫醇盐解离，因为这会导致形成[PhN(H)C(O)CH2S]-，作为阴离子，它表现出比[Tm(Ph)]ZnSCH2C(O)N(H)Ph中更强的N-H...S氢键相互作用。相应地，涉及配位硫醇盐直接烷基化的机理预计其特征为kH/kD ≤ 1，因为该反应涉及硫上负电荷的减少，从而导致N-H...S氢键相互作用减弱。
