Protonation and Reactivity towards Carbon Dioxide of the Mononuclear Tetrahedral Zinc and Cobalt Hydroxide Complexes, [Tp<sup>Bu<sup>t</sup>,Me</sup>]ZnOH and [Tp<sup>Bu<sup>t</sup>,Me</sup>]CoOH:  Comparison of the Reactivity of the Metal Hydroxide Function in Synthetic Analogues of Carbonic Anhydrase

The tris(3-<i>tert</i>-butyl-5-methylpyrazolyl)hydroborato zinc hydroxide complex [Tp<sup>Bu<sup>t</sup>,Me</sup>]ZnOH is protonated by (C<sub>6</sub>F<sub>5</sub>)<sub>3</sub>B(OH<sub>2</sub>) to yield the aqua derivative {[Tp<sup>Bu<sup>t</sup>,Me</sup>]Zn(OH<sub>2</sub>)}[HOB(C<sub>6</sub>F<sub>5</sub>)<sub>3</sub>], which has been structurally characterized by X-ray diffraction, thereby demonstrating that protonation results in a lengthening of the Zn−O bond by ca. 0.1 Å. The protonation is reversible, and treatment of {[Tp<sup>Bu<sup>t</sup>,Me</sup>]Zn(OH<sub>2</sub>)}<sup>+</sup> with Et<sub>3</sub>N regenerates [Tp<sup>Bu<sup>t</sup>,Me</sup>]ZnOH. Consistent with the notion that the catalytic hydration of CO<sub>2</sub> by carbonic anhydrase requires deprotonation of the coordinated water molecule, {[Tp<sup>Bu<sup>t</sup>,Me</sup>]Zn(OH<sub>2</sub>)}<sup>+</sup> is inert towards CO<sub>2</sub>, whereas [Tp<sup>Bu<sup>t</sup>,Me</sup>]ZnOH is in rapid equilibrium with the bicarbonate complex [Tp<sup>Bu<sup>t</sup>,Me</sup>]ZnOC(O)OH under comparable conditions. The cobalt hydroxide complex [Tp<sup>Bu<sup>t</sup>,Me</sup>]CoOH is likewise protonated by (C<sub>6</sub>F<sub>5</sub>)<sub>3</sub>B(OH<sub>2</sub>) to yield the aqua derivative {[Tp<sup>Bu<sup>t</sup>,Me</sup>]Co(OH<sub>2</sub>)}[HOB(C<sub>6</sub>F<sub>5</sub>)<sub>3</sub>], which is isostructural with the zinc complex. The aqua complexes {[Tp<sup>Bu<sup>t</sup>,Me</sup>]M(OH<sub>2</sub>)}[HOB(C<sub>6</sub>F<sub>5</sub>)<sub>3</sub>] (M = Zn, Co) exhibit a hydrogen bonding interaction between the metal aqua and boron hydroxide moieties. This hydrogen bonding interaction may be viewed as analogous to that between the aqua ligand and Thr-199 at the active site of carbonic anhydrase. In addition to the structural similarities between the zinc and cobalt complexes, [Tp<sup>Bu<sup>t</sup>,Me</sup>ZnOH] and [Tp<sup>Bu<sup>t</sup>,Me</sup>]CoOH, and between {[Tp<sup>Bu<sup>t</sup>,Me</sup>]Zn(OH<sub>2</sub>)}<sup>+</sup> and {[Tp<sup>Bu<sup>t</sup>,Me</sup>]Co(OH<sub>2</sub>)}<sup>+</sup>, DFT (B3LYP) calculations demonstrate that the p<i>K</i><sub>a</sub> value of {[Tp]Zn(OH<sub>2</sub>)}<sup>+</sup> is similar to that of {[Tp]Co(OH<sub>2</sub>)}<sup>+</sup>. These similarities are in accord with the observation that Co<sup>II</sup> is a successful substitute for Zn<sup>II</sup> in carbonic anhydrase. The cobalt hydroxide [Tp<sup>Bu<sup>t</sup>,Me</sup>]CoOH reacts with CO<sub>2</sub> to give the bridging carbonate complex {[Tp<sup>Bu<sup>t</sup>,Me</sup>]Co}<sub>2</sub>(μ-η<sup>1</sup>,η<sup>2</sup>-CO<sub>3</sub>). The coordination mode of the carbonate ligand in this complex, which is bidentate to one cobalt center and unidentate to the other, is in contrast to that in the zinc counterpart {[Tp<sup>Bu<sup>t</sup>,Me</sup>]Zn}<sub>2</sub>(μ-η<sup>1</sup>,η<sup>1</sup>-CO<sub>3</sub>), which bridges in a unidentate manner to both zinc centers. This difference in coordination modes concurs with the suggestion that a possible reason for the lower activity of Co<sup>II</sup>−carbonic anhydrase is associated with enhanced bidentate coordination of bicarbonate inhibiting its displacement.