Helical Unwinding Governs Divergent Kinetics in the Reductive Defluorination of Per- and Polyfluoroalkyl Substances.

Reductive defluorination offers an important strategy for mitigating the environmental and health risks posed by per- and polyfluoroalkyl substances (PFAS). However, the degradation rates of PFAS vary widely and cannot be explained by differences in C-F bond strength alone. Here, we use quantum chemical calculations to identify the ability of the perfluorocarbon backbone to unwind from its intrinsic helical conformation as an overlooked source of variation in PFAS reduction kinetics. Using the hydrated electron as the reference reductant, we combine the Marcus and Savéant models to show how helical unwinding shifts the kinetic preference between the stepwise and concerted reductive defluorination pathways, thereby rationalizing the structure-dependent degradation rates reported experimentally. Specifically, longer perfluorocarbon backbones tend to delocalize an excess electron through helical unwinding and form the radical intermediate required for the stepwise pathway. By contrast, the carboxylate headgroup constrains this unwinding, thereby favoring the conventional concerted pathway in which reactivity is governed by C-F bond strength. Nanoscale confinement can provide additional van der Waals stabilization, weakening the conformational constraint imposed by the carboxylate headgroup and lowering the activation free energy for the stepwise pathway. Together, these findings point to molecular conformation as a potential contributor to PFAS reduction kinetics alongside C-F bond strength and raise the prospect of accelerating degradation through microenvironment engineering.