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 {η³-HB(3-Bu^t-5-Mepz)₃}ZnOH (3-Bu^t-5-Mepz = 3-Bu^t-5-MeC₃N₂H) and {η³-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 {η³-HB(3-Bu^t-5-Mepz)₃}ZnOH reacts immediately with CO₂ to give a bicarbonate complex {·³-HB(3-Bu^t-5-Mepz)₃}Zn(OCO₂H) that has been characterized by IR spectroscopy. ¹H 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 [{η³-HB(3-Bu^t-5-Mepz)₃}Zn]₂(µ-η¹,η¹-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 {η³-HB(3,5-Prⁱ₂pz)₃}ZnOH rapidly gives the carbonate complex [{η³-HB(3,5-Prⁱ₂pz)₃}Zn]₂(µ-η¹η²-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. {η³-HB(3-Bu¹-5-Mepz)₃}ZnOH is also a functional model for carbonic anhydrase, since it effectively catalyzes the exchange of oxygen atoms between CO₂ and H₂¹⁷O. 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.