title: Reactivity of Dimeric Tetrazirconium(IV) Wells-Dawson Polyoxometalate toward Dipeptide Hydrolysis Studied by a Combined Experimental and Density Functional Theory Approach.
abstract: Detailed kinetic studies on the hydrolysis of glycylglycine (Gly-Gly) in the presence of the dimeric tetrazirconium(IV)-substituted Wells-Dawson-type polyoxometalate Na14[Zr4(P2W16O59)2(μ3-O)2(OH)2(H2O)4] · 57H2O (1) were performed by a combination of (1)H, (13)C, and (31)P NMR spectroscopies. The catalyst was shown to be stable under a broad range of reaction conditions. The effect of pD on the hydrolysis of Gly-Gly showed a bell-shaped profile with the fastest hydrolysis observed at pD 7.4. The observed rate constant for the hydrolysis of Gly-Gly at pD 7.4 and 60 °C was 4.67 × 10(-7) s(-1), representing a significant acceleration as compared to the uncatalyzed reaction. (13)C NMR data were indicative for coordination of Gly-Gly to 1 via its amide oxygen and amine nitrogen atoms, resulting in a hydrolytically active complex. Importantly, the effective hydrolysis of a series of Gly-X dipeptides with different X side chain amino acids in the presence of 1 was achieved, and the observed rate constant was shown to be dependent on the volume, chemical nature, and charge of the X amino acid side chain. To give a mechanistic explanation of the observed catalytic hydrolysis of Gly-Gly, a detailed quantum-chemical study was performed. The theoretical results confirmed the nature of the experimentally suggested binding mode in the hydrolytically active complex formed between Gly-Gly and 1. To elucidate the role of 1 in the hydrolytic process, both the uncatalyzed and the polyoxometalate-catalyzed reactions were examined. In the rate-determining step of the uncatalyzed Gly-Gly hydrolysis, a carboxylic oxygen atom abstracts a proton from a solvent water molecule and the nascent OH nucleophile attacks the peptide carbon atom. Analogous general-base activity of the free carboxylic group was found to take place also in the case of polyoxometalate-catalyzed hydrolysis as the main catalytic effect originates from the -C═O···Zr(IV) binding.
authors.affiliation: Laboratory of Bioinorganic Chemistry and ‡Laboratory of Computational Coordination Chemistry, Department of Chemistry, Katholieke Universiteit Leuven , Celestijnenlaan 200F, 3001 Leuven, Belgium.
authors.forename: Hong Giang T
authors.initials: HG
authors.lastname: Ly
authors.affiliation: Laboratory of Bioinorganic Chemistry and ‡Laboratory of Computational Coordination Chemistry, Department of Chemistry, Katholieke Universiteit Leuven , Celestijnenlaan 200F, 3001 Leuven, Belgium.
authors.forename: Tzvetan
authors.initials: T
authors.lastname: Mihaylov
authors.affiliation: Laboratory of Bioinorganic Chemistry and ‡Laboratory of Computational Coordination Chemistry, Department of Chemistry, Katholieke Universiteit Leuven , Celestijnenlaan 200F, 3001 Leuven, Belgium.
authors.forename: Gregory
authors.initials: G
authors.lastname: Absillis
authors.affiliation: Laboratory of Bioinorganic Chemistry and ‡Laboratory of Computational Coordination Chemistry, Department of Chemistry, Katholieke Universiteit Leuven , Celestijnenlaan 200F, 3001 Leuven, Belgium.
authors.forename: Kristine
authors.initials: K
authors.lastname: Pierloot
authors.affiliation: Laboratory of Bioinorganic Chemistry and ‡Laboratory of Computational Coordination Chemistry, Department of Chemistry, Katholieke Universiteit Leuven , Celestijnenlaan 200F, 3001 Leuven, Belgium.
authors.forename: Tatjana N
authors.initials: TN
authors.lastname: Parac-Vogt
mesh_terms: D002384:Catalysis; D019281:Dimerization; D006033:Glycylglycine / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D008956:Models, Chemical; D010087:Oxides / Q000737:chemistry*; D011789:Quantum Theory; D017973:Tungsten Compounds / Q000737:chemistry*; D014867:Water / Q000737:chemistry; D015040:Zirconium / Q000737:chemistry*
chemical_list: D010087:Oxides; D017973:Tungsten Compounds; D014867:Water; D006033:Glycylglycine; D015040:Zirconium