4-pyridinecarbaldehyde, hydration

Carbonic anhydrase is a zinc(II) metalloenzyme which catalyzes the hydration and dehydration of carbon dioxide, C02+H20 H+ + HC03. 25 As a result there has been considerable interest in the metal ion-promoted hydration of carbonyl substrates as potential model systems for the enzyme. For example, Pocker and Meany519 studied the reversible hydration of 2- and 4-pyridinecarbaldehyde by carbonic anhydrase, zinc(II), cobalt(II), H20 and OH. The catalytic efficiency of bovine carbonic anhydrase is ca. 108 times greater than that of water for hydration of both 2- and 4-pyridinecarbaldehydes. Zinc(II) and cobalt(II) are ca. 107 times more effective than water for the hydration of 2-pyridinecarbaldehyde, but are much less effective with 4-pyridinecarbaldehyde. Presumably in the case of 2-pyridinecarbaldehyde complexes of type (166) are formed in solution. Polarization of the carbonyl group by the metal ion assists nucleophilic attack by water or hydroxide ion. Further studies of this reaction have been made,520,521 but the mechanistic details of the catalysis are unclear. Metal-bound nucleophiles (M—OH or M—OH2) could, for example, be involved in the catalysis. 

The effect of charge on the cation is important, and is clearly seen in the hydration of 4-pyridinecarbaldehyde, 3.9. In aqueous solution the free ligand is only partially hydrated, and at equilibrium the ratio of the carbonyl form to the hydrate is about 55 45 (Fig. 3-18). Upon co-ordination of the nitrogen atom of the pyridine to ruthenium(in) in the complex [Ru(NH3)5(3.7)]3+, the ligand is over 90 % hydrated at equilibrium. 

A direct metal involvement in the hydration of an aldehyde is seen in the ruthenium(n) complex of the hydrated form of 2-pyridinecarbaldehyde (3.10). 

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