Kinetic isotope effects in chemical and biochemical reactions: physical basis and theoretical methods of calculation

© 2016 John Wiley & Sons, Ltd Kinetic isotope effects (KIEs) are a valuable tool for the analysis of chemical and biochemical reaction mechanisms. Theoretical methods of calculation of those KIEs have been developed with the aim to better understand their experimental behavior. In this review, the physical basis as well as several of those computational approaches to calculate primary hydrogen KIEs is presented. Examples of interesting chemical reactions and relevant enzymatic processes are given to demonstrate how theory is used to interpret those complex kinetic magnitudes. In particular, KIE computations within generalized transition state theory formulations are shown here to explain the temperature dependence of chemical and biochemical KIEs caused by multidimensional quantum effects contributions, such as zero point vibrational energy and quantum tunneling. An unexpected large isotope effect on the phosphorescence emission of an organic reaction is analyzed by means of KIE calculations as a function of energy and including also tunneling corrections. More quantum-based methodologies such as the Multiconfiguration Time-Dependent Hartree method and Feynman path integral simulations are discussed within the context of KIE computations. The special kinetic treatment of proton-coupled electron transfer reactions is also analyzed. WIREs Comput Mol Sci 2016, 6:584–603. doi: 10.1002/wcms.1268. For further resources related to this article, please visit the WIREs website.