The very rapid zinc(II)- and copper(II)-promoted hydrolysis of 8-acetoxyquinoline-2-carboxylic acid. A model for the rate of catalysis by carboxypeptidase A
Abstract
In the range pH 5–12 the hydrolysis of 8-acetoxyquinoline-2-carboxylic acid (EH) follows the rate law, rate =k0[E–]+kOH[E–][OH–] with k0= 1.67 × 10–4 s–1 and kOH= 0.84 dm3 mol–1 s–1 at 25 °C and I= 0.1 mol dm–3. Activation parameters for the ‘spontaneous’ reaction (ΔH‡= 57.3 kJ mol–1, ΔS‡=–159 J K–1 mol–1) and the solvent deuterium-isotope effedt (kH2O/kD2O= 2.5) support a mechanism involving intramolecular general-base catalysis by the quinoline nitrogen. The 1 : 1 metal complexes of the ester, [ME]+(M = ZnII and CuII), undergo base hydrolysis ca. 2 × 108 times faster than the deprotonated ligand (E–). The metal-promoted reactions involve intramolecular attack by co-ordinated hydroxide ion and this effect in conjunction with a perturbation of 6 pKa units in the acidity of the conjugate acid of the leaving group leads to rates of hydrolysis (k 5 × 101– 5 × 103 s–1) comparable to the reported values of kcat for the hydrolysis of a good ester substrate by the zinc metalloenzyme carboxypeptidase A (kcatca. 2.3 × 102 s–1).