EaStChem, University of Edinburgh, Joseph Black Building, David Brewster Road, Edinburgh EH9 3FJ, U.K.
School of Health Sciences, The University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, U.K.
J Am Chem Soc. 2021 Dec 22;143(50):21079-21099. doi: 10.1021/jacs.1c07351. Epub 2021 Dec 6.
Chemists have many options for elucidating reaction mechanisms. Global kinetic analysis and classic transition-state probes (e.g., LFERs, Eyring) inevitably form the cornerstone of any strategy, yet their application to increasingly sophisticated synthetic methodologies often leads to a wide range of indistinguishable mechanistic proposals. Computational chemistry provides powerful tools for narrowing the field in such cases, yet wholly simulated mechanisms must be interpreted with great caution. Heavy-atom kinetic isotope effects (KIEs) offer an exquisite but underutilized method for reconciling the two approaches, anchoring the theoretician in the world of calculable observables and providing the experimentalist with atomistic insights. This Perspective provides a personal outlook on this synergy. It surveys the computation of heavy-atom KIEs and their measurement by NMR spectroscopy, discusses recent case studies, highlights the intellectual reward that lies in alignment of experiment and theory, and reflects on the changes required in chemical education in the area.
化学家在阐明反应机制时有多种选择。全局动力学分析和经典的过渡态探针（例如，LFERs、Eyring）不可避免地构成任何策略的基石，但将它们应用于越来越复杂的合成方法通常会导致一系列难以区分的机制建议。在这种情况下，计算化学为缩小研究领域提供了强大的工具，但必须非常谨慎地解释完全模拟的机制。重原子动力学同位素效应 (KIE) 提供了一种精致但未充分利用的方法来协调这两种方法，使理论家扎根于可计算可观测量的世界，并为实验家提供原子水平的见解。本观点提供了对此协同作用的个人看法。它调查了重原子 KIE 的计算及其通过 NMR 光谱的测量，讨论了最近的案例研究，强调了实验和理论一致所带来的智力回报，并反思了该领域化学教育所需的变化。
