Unifying path-dependent and thermodynamic descriptors of asynchronicity in double proton transfer reactions

In this work, we develop a unified thermodynamic-kinetic framework to quantify and interpret asynchronicity in concerted multibond reactions. As a model system, we analyze approximately 80 double proton transfer (DPT) reactions in 105 complexes stabilized by double hydrogen bonds, spanning a broad structural diversity of proton donors and acceptors. We introduce a thermodynamic asynchronicity descriptor, η, formulated from acid-base thermochemical cycles and interpreted using More O'Ferrall-Jencks diagrams, and link it to a path-dependent kinetic descriptor based on the reaction force constant, κ(ξ), whose fine structure in the transition region diagnoses the degree of coupling between the two proton-transfer events. We show that, for the thermodynamically asymmetric subset (ΔE⁰ ≠ 0), classification by η or by the topology of κ(ξ) reorganizes dispersed BEP data into nearly parallel correlations with similar slopes and a systematically lower intercept for more asynchronous processes, consistent with a reduction in the intrinsic barrier as asynchronicity increases. Furthermore, we establish a nonlinear relationship between η and the transition-region width, Δξ_TS, which provides a quantitative bridge between thermodynamic bias and kinetic decoupling and enables the identification of outliers in which kinetic asynchronicity arises despite minimal thermodynamic imbalance (PNPS). Taken together, this approach reconciles thermodynamic and path-dependent perspectives on asynchronicity and offers a general strategy for rationalizing deviations from BEP behavior in concerted transformations.