Conformational Dynamics for Catalysis beyond the Sabatier Limit

Abstract Conformational changes occur throughout biology and are implicated in numerous phenomena, including enzyme catalysis where their role remains controversial. Conformational dynamics have also been observed in small-molecule catalysis, yet a lack of systematic study means that their influence is poorly understood. Here, we highlight how advances in chemical reaction network mathematics, alongside the translation of the Sabatier principle from heterogeneous to homogeneous catalysis, now enable the behavior of conformationally dynamic catalysts to be understood from first principles. We demonstrate that for common classes of reaction mechanisms, catalyst conformational dynamics can, in principle, cause large rate enhancements relative to each of the catalyst’s individual conformations, as well as rate enhancements of orders of magnitude above the Sabatier limit. This quantitative understanding reveals how particular features of a catalyst or reaction mechanism govern catalytic rate, which allows us to propose general design principles that might be exploited by existing or future conformationally dynamic catalysts. The understanding that conformational dynamics can allow a catalyst to overcome otherwise fundamental rate limits should have broad implications across chemistry and biology.