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^–]+k_OH[E^–][OH^–] with k₀= 1.67 × 10^–4 s^–1 and k_OH= 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 (k_H2O/k_D2O= 2.5) support a mechanism involving intramolecular general-base catalysis by the quinoline nitrogen. The 1 : 1 metal complexes of the ester, [ME]⁺(M = Zn^II and Cu^II), 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 pK_a 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 k_cat for the hydrolysis of a good ester substrate by the zinc metalloenzyme carboxypeptidase A (k_catca. 2.3 × 10² s^–1).