Kinetic Study of CO(2) Hydration by Small-Molecule Catalysts with A Second Coordination Sphere that Mimic the Effect of the Thr-199 Residue of Carbonic Anhydrase

Zinc complexes were synthesized as catalysts that mimic the ability of carbonic anhydrase (CA) for the CO(2) hydration reaction (H(2)O + CO(2) → H(+) + HCO(3)(−)). For these complexes, a tris(2-pyridylmethyl)amine (TPA) ligand mimicking only the active site, and a 6-((bis(pyridin-2-ylmethyl)amino)methyl)pyridin-2-ol (TPA-OH) ligand mimicking the hydrogen-bonding network of the secondary coordination sphere of CA were used. Potentiometric pH titration was used to determine the deprotonation ability of the Zn complexes, and their pK(a) values were found to be 8.0 and 6.8, respectively. Stopped-flow spectrophotometry was used to confirm the CO(2) hydration rate. The rate constants were measured to be 648.4 and 730.6 M(−1)s(−1), respectively. The low pK(a) value was attributed to the hydrogen-bonding network of the secondary coordination sphere of the catalyst that mimics the behavior of CA, and this was found to increase the CO(2) hydration rate of the catalyst.