Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.17.3.2 (xanthine oxidase)
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The synthesis of a heterodinucleating ligand LH2 (LH2 = (E)-3-(((2,7-di-tert-butyl-9,9-dimethyl-5-((pyridin-2-ylmethylene)amino)-9H-xanthen-4-yl)amino)methyl)benzene-1,2-diol) was undertaken toward a functional model of the bimetallic active site found in Mo-Cu carbon monoxide dehydrogenase (Mo-Cu CODH), and to understand the origins of heterobimetallic cooperativity exhibited by the enzyme. LH2 features a hard potentially dianionic catechol chelate for binding Mo(vi) and a soft iminopyridine chelate for binding Cu(i). Treatment of LH2 with either Cu(i) or M(vi) (M = Mo, W) sources leads to the anticipated site-selective incorporation of the respective metals. While both [CuI(LH2)]+ and [MVIO3(L)]2- complexes are stable in the solid state, [MVIO3(L)]2- complexes disproportionate in solution to give [MVIO2(L)2](NEt4)2 complexes, with [MVIO4]2- as the by-product. The incorporation of BOTH Mo(vi) and Cu(i) into L forms a highly reactive heterobimetallic complex [MoVIO3CuI(L)](NEt4)2, whose formation and reactivity was interrogated via1H NMR/UV-vis spectroscopy and DFT calculations. These studies reveal that the combination of the two metals triggers oxidation reactivity, in which a nucleophilic Mo(vi) trioxo attacks Cu(i)-bound imine. The major product of the reaction is a crystallographically characterized molybdenum(vi) complex [Mo(L')O2](NEt4) coordinated by a modified ligand L' that contains a new C-O bond in place of the imine functionality. This observed hydroxylation reactivity is consistent with the postulated first step of Mo-Cu CODH (nucleophilic attack of the Mo(vi)-oxo on the Cu(i)-bound electrophilic CO) and xanthine oxidoreductase (nucleophilic attack of Mo(vi)-oxo on the electrophilic xanthine carbon).
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PMID:Cooperative bimetallic reactivity of a heterodinuclear molybdenum-copper model of Mo-Cu CODH. 2994 11