title: Methanethiol Binding Strengths and Deprotonation Energies in Zn(II)-Imidazole Complexes from M05-2X and MP2 Theories: Coordination Number and Geometry Influences Relevant to Zinc Enzymes.
abstract: Zn(II) is used in nature as a biocatalyst in hundreds of enzymes, and the structure and dynamics of its catalytic activity are subjects of considerable interest. Many of the Zn(II)-based enzymes are classified as hydrolytic enzymes, in which the Lewis acidic Zn(II) center facilitates proton transfer(s) to a Lewis base, from proton donors such as water or thiol. This report presents the results of a quantum computational study quantifying the dynamic relationship between the zinc coordination number (CN), its coordination geometry, and the thermodynamic driving force behind these proton transfers originating from a charge-neutral methylthiol ligand. Specifically, density functional theory (DFT) and second-order perturbation theory (MP2) calculations have been performed on a series of [(imidazole)nZn-S(H)CH3](2+) and [(imidazole)nZn-SCH3](+) complexes with the CN varied from 1 to 6, n = 0-5. As the number of imidazole ligands coordinated to zinc increases, the S-H proton dissociation energy also increases, (i.e., -S(H)CH3 becomes less acidic), and the Zn-S bond energy decreases. Furthermore, at a constant CN, the S-H proton dissociation energy decreases as the S-Zn-(ImH)n angles increase about their equilibrium position. The zinc-coordinated thiol can become more or less acidic depending upon the position of the coordinated imidazole ligands. The bonding and thermodynamic relationships discussed may apply to larger systems that utilize the [(His)3Zn(II)-L] complex as the catalytic site, including carbonic anhydrase, carboxypeptidase, β-lactamase, the tumor necrosis factor-α-converting enzyme, and the matrix metalloproteinases.
authors: Department of Chemistry and Physics, Southwestern Oklahoma State University , Weatherford, Oklahoma 73096, United States.
authors: Douglas P
authors: DP
authors: Linder
authors: Department of Chemistry and Biochemistry, North Dakota State University , Fargo, North Dakota 58108, United States.
authors: Kenton R
authors: KR
authors: Rodgers
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000378:metabolism; D008667:Metalloproteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism; D011522:Protons; D011789:Quantum Theory; D013438:Sulfhydryl Compounds / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics; D015032:Zinc / Q000737:chemistry* / Q000378:metabolism
chemical_list: D007093:Imidazoles; D008667:Metalloproteins; D009942:Organometallic Compounds; D011522:Protons; D013438:Sulfhydryl Compounds; C005231:methylmercaptan; C029899:imidazole; D015032:Zinc