A Descriptor-Based Approach to Predict the Catalytic Activity of Zinc CO2 Hydration Catalysts

Carbonic anhydrase (CA) catalyzes CO2 hydration with turnover frequencies approaching 106 s–1, but native enzymes lack stability under conditions typical of industrial carbon capture. Small-molecule zinc mimics can be more stable under harsh conditions, but product inhibition by bicarbonate limits efficiency. A general framework for predicting turnover across ligand scaffolds has remained elusive. We report the analysis, by experiment and computation, of speciation and catalytic activity of zinc complexes as CA mimics. A literature data set of twelve Zn-ligand complexes was constructed, and the binding free energy (ΔGbind) of bicarbonate to zinc was calculated by DFT with DLPNO-CCSD(T) refinement. ΔGbind strongly correlates with the intrinsic rate constants of these Zn-ligand complexes for CO2 hydration with R2 = 0.90 at pH 9, 25 °C, and saturated CO2 (1 atm). By comparison, combining the commonly used descriptors ΣE(2), qZn, and %Vburied resulted in R2 = 0.74. Examining additional Zn catalysts (for example, the coordination species [ZnL4(OH)]+, where L is 1-methylimidazole) revealed that chemical speciation must be accounted for to describe the observed dependence of catalytic activity on ligand stoichiometry. Furthermore, accurate ranking of catalytic activity for several of the modified cyclens considered requires accounting for steric congestion (%Vburied), as ΔGbind alone does not capture active-site occlusion. These results define a transferable framework that integrates ΔGbind, speciation, and steric properties to enable the design of Zn-based CO2 hydration catalysts.