论文标题
叠氮化物 - 烷基Huisgen Cycloadition的反应机制
The Reaction Mechanism of the Azide-Alkyne Huisgen Cycloaddition
论文作者
论文摘要
叠氮化物 - 阿尔基（Azide-Alkyne Huisgen Cyclation）在点击化学中具有关键作用，并将其作为药物和药物化学中有力的工具配置。尽管该反应已经在很大程度上进行了研究，但关于其机制的辩论仍在进行中。在这项工作中，我们使用元动力计算机模拟研究了过程的动态方面。我们专注于决定反应过程并表征该过程的自由能格局的构象方面。为了正确捕获该过程的热力学，我们使用谐波线性判别分析选择最佳的集体变量。结果定性地证实了实验证据，并深入了解取代基的作用和可能的过渡机制。
The azide-alkyne Huisgen cycloaddition has a key role in click chemistry and configures as powerful tool in pharmaceutical and medicinal chemistry. Although this reaction has already been largely studied, there is an ongoing debate about its mechanism. In this work we study the dynamical aspects of the process using metadynamics computer simulation. We focus on the conformational aspects that determine the course of the reaction and characterize the free energy landscape of the process. To properly capture the thermodynamics of the process we select optimal collective variables using harmonic linear discriminant analysis. The results confirm the experimental evidence qualitatively and give insight on the role of the substituents and the possible transition mechanisms.
