title: Model complexes of cobalt-substituted matrix metalloproteinases: tools for inhibitor design.
abstract: The tetrahedral cobalt(II) complex [(Tp(Ph,Me))CoCl] (Tp(Ph,Me) = hydrotris(3,5-phenylmethylpyrazolyl)borate) was combined with several hydroxypyridinone, hydroxypyridinethione, pyrone, and thiopyrone ligands to form the corresponding [(Tp(Ph,Me))Co(L)] complexes. X-ray crystal structures of these complexes were obtained to determine the mode of binding for each ligand L. The structures show that the [(Tp(Ph,Me))Co(L)] complexes are pentacoordinate complexes, with a general tendency toward square pyramidal geometry. The electronic, EPR, and paramagnetic NMR spectroscopy of the [(Tp(Ph,Me))Co(L)] complexes have been examined. The frozen-solution EPR spectra are indicative of pentacoordination in frozen solution, while the NMR indicates some dynamics in ligand binding. The findings presented here suggest that [(Tp(Ph,Me))Co(L)] complexes can be used as spectroscopic references for investigating the mode of inhibitor binding in metalloproteinases of medicinal interest. Potential limitations when using cobalt(II) model complexes are also discussed.
authors.affiliation: Department of Chemistry and Biochemistry, University of California-San Diego, La Jolla, CA 92093-0358, USA.
authors.forename: Faith E
authors.initials: FE
authors.lastname: Jacobsen
authors.forename: Robert M
authors.initials: RM
authors.lastname: Breece
authors.forename: William K
authors.initials: WK
authors.lastname: Myers
authors.forename: David L
authors.initials: DL
authors.lastname: Tierney
authors.forename: Seth M
authors.initials: SM
authors.lastname: Cohen
mesh_terms: D001665:Binding Sites; D003035:Cobalt / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D061965:Matrix Metalloproteinase Inhibitors; D009942:Organometallic Compounds; D011480:Protease Inhibitors; D003035:Cobalt; D020782:Matrix Metalloproteinases