A structural and functional model of dinuclear metallophosphatases

Hydrolysis of four substituted phenyl phosphate monoesters, each coordinate d to a dinuclear Cocm, complex, was studied ([Co-2(tacn)(2)(OH)(2){O3P(OAr) }](2+); tacn = 1,4,7-triazacyclononane; substituent m-F, p-NO2 (5a); p-NO2 (5b); m-NO2 (5c); unsubstituted (5d)). Crystallographic data reveal that 5b is an excellent structural model of the active sites of several phosphatas es: protein phosphatase-l, kidney bean purple acid phosphatase, and calcine urin-alpha. All of these structures consist of two octahedral metal complex es connected by two oxygen bridges, forming a four-membered-ring diamond co re. The pH-rate profile and the O-18 labeling experiment for the hydrolysis of 5b indicates that the oxide bridging the two metal centers in the diamo nd core is acting as an intramolecular nucleophile for cleaving the coordin ated phosphate monoester. The phosphate monoesters in this model system are hydrolyzed more rapidly than those in previously reported model systems. H ence, the dinuclear cobalt complexes 5 appear to be excellent structural an d functional models of the above-mentioned phosphatases. The rate of hydrol ysis of 5 is highly sensitive to the basicity of the leaving group (beta(1g ) 1.10). Detailed analysis of the leaving group dependence for the hydrolys is of 5 indicates only a partial negative charge on the leaving group oxyge n at the transition state, further supporting the nucleophilic mechanism.