A Fast and Accurate Semi-Empirical Approach for Hydrogen-Exchange Kinetic Isotope Effect Evaluation

The kinetic isotope effect (KIE) is essential in various chemical applications from reaction mechanism studies to tritium removal from water, however, its evaluation is associated with computational difficulties, mainly related to the correct determination of the geometry of the transition state. Traditional KIE evaluation relies on experimental measurements or computational approaches like density functional theory (DFT), which are often costly and whose accuracy strongly depends on the level of theory used. Here, we present a novel semi-empirical method for rapid and precise KIE estimation in proton-exchange reactions. By refining transition state identification through an iterative surface scan, our approach significantly improves accuracy while maintaining computational efficiency. Benchmarking against experimental data demonstrates superior performance compared to both DFT and conventional semi-empirical methods. Additionally, validation with tritium exchange reactions confirms its robustness. The computational implementation is freely available, facilitating its integration into future research.