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Abstract：
Neutral N⁻heterocyclic carbene gold(I) compounds such as IMeAuCl are widely used both in homogeneous catalysis and, more recently, in medicinal chemistry as promising antitumor agents. In order to shed light on their reactivity with protein side chains, we have carried out density functional theory (DFT) calculations on the thermodynamics and kinetics of their reactions with water and various nucleophiles as a model of plausible protein binding sites such as arginine, aspartic acid, asparagine, cysteine, glutamic acid, glutamine, histidine, lysine, methionine, selenocysteine, and the N-terminal group. In agreement with recent experimental data, our results suggest that IMeAuCl easily interacts with all considered biological targets before being hydrated-unless sterically prevented-and allows the establishment of an order of thermodynamic stability and of kinetic reactivity for its binding to protein residues.
摘要：
中性氮杂环卡宾金(I)化合物如IMeAuCl被广泛用于均相催化和,最近,在药物化学中作为有前途的抗肿瘤药物。为了阐明它们与蛋白质侧链的反应性，我们已经对它们与水和各种亲核试剂反应的热力学和动力学进行了密度泛函理论（DFT）计算，作为可能的蛋白质结合位点（如精氨酸）的模型，天冬氨酸,天冬酰胺,半胱氨酸,谷氨酸，谷氨酰胺,组氨酸,赖氨酸，蛋氨酸,硒代半胱氨酸，和N端组。与最近的实验数据一致，我们的结果表明,IMeAuCl在水合之前很容易与所有考虑的生物靶标相互作用-除非在空间上阻止-并且允许建立其与蛋白质残基结合的热力学稳定性和动力学反应性的顺序.
