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Inhibitory interactions between tripodal chelating ligands and matrix metalloproteinases
218
Journal of Inorganic Biochemistry 96 (2003)
Dioxygen activation by low valent nickel complexes: characterization of new Ni-dioxygen intermediates Charles G Riordan, University OfDeIaware, UnitedStates Koyu Fujita, University of Delaware, United States Matthew Kieber-Emmons, University of Delaware, United States Beaven S Mandimutsira, University of Delaware, United States A series of Ni(1) complexes supported by the [S3] borato ligands, [PhB(CH,SR),] (abbreviated PhTtR) have been prepared and their reactivity towards dioxygen assayed, Scheme. Ligand design permits for the interception of distinct, thermallysensitive intermediates. For example, [PhTttBu]Ni(CO) is oxygenated to the purple, bis(mu-oxo) dimer, ([PhTttBu]Ni),(yO),. In contrast, the larger, adamantyl-supported complex, [PhTtAd]Ni(CO) reacts with dioxygen to yield the brown, monomeric species, [PhTtAd]Ni(O,). This complex is a useful precursor for the construction of mixed metal species.Each intermediate is characterized uniquely by its combined UV-visible, NMR, resonance Raman and Ni EXAFS spectroscopic features. Density functional theory analysis and reactivity studies of the novel intermediates will be presented.
Inhibitory
Interactions between Tripodal Chelating Ligands and Matrix Metalloproteinases
Kenton R Rodgers North Dakota State University, Department of Chemistry, United States Hongshan He, North Dakota State University, Department of Chemistry, United States Douglas P Linder, North Dakota State University, Department of Chemistry, United States Indrani Chakraborty, North Dakota State University Department of Chemistry, UnitedStates Matrix metalloproteinases (MMPs) are Zn(II)-containing endopeptidases that play crucial roles in mammalian tissue homeostasis. Dysfunction in MMPs is correlated with a wide variety of diseasestates including numerous cancers, arthritis, periodontal disease, and opening ofthe blood-brain barrier. These enzymes have as their substratesvarious forms of collagen. Their specificities for particular types of collagen are relatively low, which makes targeting of a specific MMP difficult. We have undertaken the synthesis of tripodal chelating inhibitors based on the tren scaffold. The inhibitors are conveniently modified, either symmetrically or asymmetrically, to facilitate targeting of specific MM&. Interaction of these compounds with MMP active sites are being investigated via inhibition studies, characterization of model complexes, and molecular modeling. Results on all three aspects of this study will be presented.
Journal of Inorganic Biochemistry 96 (2003)
Dioxygen activation by low valent nickel complexes: characterization of new Ni-dioxygen intermediates Charles G Riordan, University OfDeIaware, UnitedStates Koyu Fujita, University of Delaware, United States Matthew Kieber-Emmons, University of Delaware, United States Beaven S Mandimutsira, University of Delaware, United States A series of Ni(1) complexes supported by the [S3] borato ligands, [PhB(CH,SR),] (abbreviated PhTtR) have been prepared and their reactivity towards dioxygen assayed, Scheme. Ligand design permits for the interception of distinct, thermallysensitive intermediates. For example, [PhTttBu]Ni(CO) is oxygenated to the purple, bis(mu-oxo) dimer, ([PhTttBu]Ni),(yO),. In contrast, the larger, adamantyl-supported complex, [PhTtAd]Ni(CO) reacts with dioxygen to yield the brown, monomeric species, [PhTtAd]Ni(O,). This complex is a useful precursor for the construction of mixed metal species.Each intermediate is characterized uniquely by its combined UV-visible, NMR, resonance Raman and Ni EXAFS spectroscopic features. Density functional theory analysis and reactivity studies of the novel intermediates will be presented.
Inhibitory
Interactions between Tripodal Chelating Ligands and Matrix Metalloproteinases
Kenton R Rodgers North Dakota State University, Department of Chemistry, United States Hongshan He, North Dakota State University, Department of Chemistry, United States Douglas P Linder, North Dakota State University, Department of Chemistry, United States Indrani Chakraborty, North Dakota State University Department of Chemistry, UnitedStates Matrix metalloproteinases (MMPs) are Zn(II)-containing endopeptidases that play crucial roles in mammalian tissue homeostasis. Dysfunction in MMPs is correlated with a wide variety of diseasestates including numerous cancers, arthritis, periodontal disease, and opening ofthe blood-brain barrier. These enzymes have as their substratesvarious forms of collagen. Their specificities for particular types of collagen are relatively low, which makes targeting of a specific MMP difficult. We have undertaken the synthesis of tripodal chelating inhibitors based on the tren scaffold. The inhibitors are conveniently modified, either symmetrically or asymmetrically, to facilitate targeting of specific MM&. Interaction of these compounds with MMP active sites are being investigated via inhibition studies, characterization of model complexes, and molecular modeling. Results on all three aspects of this study will be presented.