Volcano relationship between oxygen affinity and intrinsic activity in aldol condensation over metal oxides

Aldol condensation is a fundamental carbon–carbon coupling reaction for upgrading oxygenates; however, the intrinsic catalyst function governing carbonyl activation and enolization—and thus the reactivity—remains unclear, particularly in the absence of a reliable descriptor. Here, we establish oxygen affinity as a mechanistically relevant descriptor linking catalyst–oxygenate interactions to intrinsic activity. A volcano-type relationship is revealed over a series of metal oxides in benzaldehyde-acetone aldol condensation, demonstrating that catalytic performance is maximized at an intermediate interaction strength. Establishing this relationship requires quantitative determination of active-site density to evaluate intrinsic activity, and independent assessment of interaction strength. We employ complementary and cross-validated experimental methods integrating isothermal desorption, infrared spectroscopy, and pulse chemisorption. Furthermore, substituent effects show that the optimal affinity regime shifts systematically with substrate electronic properties, indicating that descriptor–reactivity relationships depend on substrate electronic properties. This work provides a quantitative basis for descriptor-based catalyst design in oxygenate transformations.