TRIS(PYRAZOLYL)HYDROBORATOZINC HYDROXIDE COMPLEXES AS FUNCTIONAL MODELS FOR CARBONIC-ANHYDRASE - ON THE NATURE OF THE BICARBONATE INTERMEDIATE

The reactions of (CO2 With the zinc hydroxide complexes {eta3-HB(3-But-5-MePZ)3}ZnOH (3-But-5-Mepz = 3-But-5-MeC3N2H) and {eta3-HB(3,5-Pri2pz)3}ZnOH (3,5-Pri2pz = 3,5-Pri2C3N2H), which are proposed to be structural models for the active site of the enzyme carbonic anhydrase, have been investigated. The hydroxide {eta3-HB(3-But-5-Mepz)3}ZnOH reacts immediately with CO2 to give a bicarbonate complex {eta3-HB(3-But-5-Mepz)3}Zn(OCO2H) that has been characterized by IR spectroscopy. H-1 NMR studies reveal that the reaction with CO2 is rapid and reversible on the NMR time scale at room temperature. A subsequent slower transformation involves the formation of the carbonate complex [{eta3-HB(3-But-5-MePZ)3}Zn]2(mu-eta1,eta1-CO3), in which the carbonate ligand bridges the two zinc centers with a symmetric unidentate coordination mode. In contrast, the corresponding reaction of the less sterically encumbered hydroxide {eta3-HB(3,5-Pri2pz)3}ZnOH rapidly gives the carbonate complex [{eta3-HB(3,5-Pri2pzZ)3}Zn]2(mu-eta1,eta2-CO3), in which the carbonate ligand bridges the two zinc centers in an asymmetric manner and is unidentate to one zinc center but bidentate to the other. {Eta3-HB(3-But-5-MePZ)3}ZnOH is also a functional model for carbonic anhydrase, since it effectively catalyzes the exchange of oxygen atoms between CO2 and (H2O)-O-17. Structural and reactivity studies on the unidentate and bidentate carbonate complexes, together with structural studies on a series of nitrate complexes, suggest that facile access to a unidentate bicarbonate species may be a critical factor for carbonic anhydrase activity.