title: Ternary ligand-zinc-hydroxamate complexes.
abstract: Because of the importance of the hydroxamic acid functional group in zinc protease inhibitors, we have measured the stability constants of the ternary complex LMG, where L is series of tridentate and tetradentate ligands containing amino, carboxylate, pyridyl, and/or imidazolyl groups as enzyme models and G is the guest molecule, acetohydroxamate or N-methylacetohydroxamate. All measurements were determined by pH titration which gave reproducible and reasonable results. A general correlation between binding of LMG and that of LM showed ligands that strongly chelated zinc gave less LMG formation. Surprisingly, no correlation was observed between ligand charge and LMG formation even though the guest, acetohydroxamate, is anionic. The pH value of the maximum formation of the ternary complex is also correlated to the acidity of zinc-bound water; more acidic zinc-bound water results in a maximum ternary complex formation at lower pH value.
authors.affiliation: Department of Chemistry, New York University, New York, New York 10003, USA.
authors.forename: Yu-Hung
authors.initials: YH
authors.lastname: Chiu
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Gabriel
authors.forename: James W
authors.initials: JW
authors.lastname: Canary
mesh_terms: D001665:Binding Sites; D006863:Hydrogen-Ion Concentration; D006877:Hydroxamic Acids / Q000737:chemistry*; D008024:Ligands; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000737:chemistry*; D008956:Models, Chemical; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D011199:Potentiometry; D011480:Protease Inhibitors / Q000737:chemistry*; D013816:Thermodynamics; D015032:Zinc / Q000737:chemistry*
chemical_list: D006877:Hydroxamic Acids; D008024:Ligands; D061965:Matrix Metalloproteinase Inhibitors; D009942:Organometallic Compounds; D011480:Protease Inhibitors; D020782:Matrix Metalloproteinases; D015032:Zinc