Partial Deuteration Tunes Reactivity of Solids in a Mechanochemical Transformation by Inducing an Unexpected Kinetic Isotope Effect

We report a deuterium kinetic isotope effect (KIE) in the mechanically driven formation and polymorphic transformation of a hydrogen-bonded organic salt, monitored in situ by synchrotron powder X-ray diffraction and Raman spectroscopy. Surprisingly, no measurable KIE is observed in the salt formation step (which necessarily involves H transfer), whereas a pronounced KIE emerges in the subsequent polymorphic transformation (involving only supramolecular rearrangement). Deuteration delays the onset of the polymorphic transformation and slows the transformation rate, with the fully deuterated system showing an approximately 3-fold decrease in rate and partially deuterated mixtures exhibiting intermediate kinetics. An impact-based kinetic model captures the isotope-dependent trends, while solid-state DFT including vibrational contributions does not indicate an isotope-dependent change in relative phase stability, supporting a primarily kinetic origin of the KIE. These results identify partial deuteration as a practical handle for tuning the solid-state reactivity.