Tris(pyrazolyl)hydroboratozinc Hydroxide Complexes as Functional Models for Carbonic Anhydrase: On the Nature of the Bicarbonate Intermediate

Adrian Looney, Runyu Han, Kristopher McNeill, Gerard Parkin

Research output: Contribution to journalArticlepeer-review

190 Scopus citations

Abstract

The reactions of CO2 with the zinc hydroxide complexes {η3-HB(3-But-5-Mepz)3}ZnOH (3-But-5-Mepz = 3-But-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-But-5-Mepz)3}ZnOH reacts immediately with CO2 to give a bicarbonate complex {·3-HB(3-But-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-But-5-Mepz)3}Zn]2(µ-η11-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.

Original languageEnglish (US)
Pages (from-to)4690-4697
Number of pages8
JournalJournal of the American Chemical Society
Volume115
Issue number11
DOIs
StatePublished - Jun 1 1993

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