The alkylation mechanism of zinc-bound thiolates depends upon the zinc ligands.
The alkylation mechanism of zinc-bound thiolates depends upon the zinc ligands.
复制标题
锌结合硫醇盐的烷基化机制取决于锌配体。
作者：
D. Picot;G. Ohanessian;G. Frison
锌结合硫醇盐的烷基化发生在酶的催化和结构锌位点。最近的仿生研究引发了关于硫醇盐烷基化中哪种机制起作用的争议。基于这些仿生复合物之一，我们设计了一系列模型，可以评估电荷，配体性质和氢键对硫反应性的作用。这些配合物与碘甲烷的反应，导致硫醚和碘化锌配合物，已被检查的密度泛函理论计算，在气相中，以及在水溶液中。在所有情况下，S（N）2反应优于σ键复分解。净电荷和氢键对硫醇盐的亲核性起着重要的作用。我们发现，实验观察到的机制多样性可以解释的净电荷的复合物的差异。双阴离子络合物遵循解离途径，而缔合的是优选的中性系统。
Alkylation of zinc-bound thiolates occurs in both catalytic and structural zinc sites of enzymes. Recent biomimetic studies have led to a controversy as to which mechanism is operative in thiolate alkylation. Building on one of these biomimetic complexes, we have devised a series of models that allow for an appraisal of the roles of charge, ligand nature, and hydrogen bonding to sulfur on reactivity. The reactions of these complexes with methyl iodide, leading to thioethers and zinc iodide complexes, have been examined by density functional theory calculations, in the gas phase as well as in an aqueous solution. In all cases, a S(N)2 reaction is favored over sigma-bond metathesis. Both the net electronic charge and the hydrogen bond play a significant role in the nucleophilicity of the thiolate. We find that the mechanistic diversity observed experimentally can be explained by the difference in the net charge of the complexes. A dianionic complex follows a dissociative pathway, whereas an associative one is preferred for a neutral system.