[(H2O)Zn(Imidazole)n]2+: the vital roles of coordination number and geometry in Zn–OH2 acidity and catalytic hydrolysis

The Zn(II)–(Imidazole(ate))n coordination motif occurs in numerous biochemical systems, including carbonic anhydrase and the matrix metalloproteinases (MMPs). Additionally, it has been used in synthetic materials, such as the zinc-based zeolitic imidazolate framework (ZIF) structures. Zinc centers in these systems typically act as Lewis acids that form complexes with small molecules, such as H2O, which is activated catalytically toward a number of important and useful hydrolysis reactions. The results reported herein from density functional theory (M05-2X) and ab initio (MP2 and CCSD(T)) calculations demonstrate that both the coordination number and the molecular geometry have a sizable impact on the binding strength, deprotonation energy, and acidity of the Zn(II) coordinated water. Through a series of quantum mechanical calculations on [(ImH)nZn–OH2]2+ complexes (n = 1–5), both the solution-phase pKa and the gas-phase proton dissociation energy significantly increase as n increases. While this should not be too surprising, the Zn–OH2 bond dissociation energies and bond lengths don’t necessarily undergo a concurrent decrease, and therefore would be of limited use as a prediction tool regarding Zn–OH2 acidity. In an effort to dissect the impacts of coordination number and molecular geometry on these thermodynamic parameters, we performed constrained geometry optimizations on the three- (n = 2) and four-coordinate (n = 3) complexes. These calculations surprisingly reveal a marked impact on the pKa and proton dissociation energy of the coordinated water, upon exclusive changes in the Zn(II) coordination geometry, whether in the gas-phase or in aqueous solution. We discuss the relevance of these results to the catalytic peptide hydrolysis mechanism of the MMPs and possible implications for catalytic activity within or on the surfaces of ZIFs.