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

Abstract

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.

Making Base-Assisted C–H Bond Activation by Cp*Co(III) Effective: A Noncovalent Interaction-Inclusive Theoretical Insight and Experimental Validation

“…A recent review by Hartwig et al is particularly informative of the pitfalls in drawing conclusions from experimental KIEs without the complementary knowledge of reaction energy profiles that theoretical support can provide. To probe the CMD mechanism and its consistency with the experimental apparent KIE, we applied the simplified Bigeleisen equation − to compute KIEs of the key steps of the CMD mechanism. Quite interestingly this equation has been seldom used in investigations of the CMD mechanism.…”

Large Anharmonic Effects on Tunneling and Kinetics: Reaction of Propane with Muonium

“…Kinetic isotope effects (KIEs) can be used to elucidate mechanisms and, because they are especially sensitive to tunneling and zero-point energy (ZPE), they provide quantitative tests of the reliability of simulations. − Inclusion of quantal effects in simulations of complex processes such as enzyme catalysis, proton-coupled electron transfer, and hydrogen-atom transfer in atmospheric reactions is critical for calculating accurate rate constants and KIEs. ,,,− Here, we demonstrate the importance of reaction-coordinate-dependent anharmonicity for calculating KIEs.…”

Heavy-Atom Kinetic Isotope Effects: Primary Interest or Zero Point?

“…Under semiclassical TST, KIEs can be expressed in terms of isotopologous differences in free energies of activation (ΔΔ ⧧ G L,H = Δ ⧧ G L – Δ ⧧ G H ; eq ) or, equivalently, in terms of molecular partition functions for the ground state (A; q L,H (A) ) and transition state (⧧; q L,H (⧧) ; eq ) of a reaction. κ L,H ( T ) are the transmission coefficients for the two isotopologous pathways. …”