Effects of pH and ligands on the metals-catalyzed hydrolysis of clioquinol conjugates.

Abstract

Metals-catalyzed hydrolysis of clioquinol (C) conjugates, namely C-glucuronide (CG) and C-sulfate (CS), was examined to investigate the effects of pH and ligands on the activities. The initial rates of hydrolysis (Vo) of CG and CS were measured as a function of pH in systems containing various metals. The profiles of Vo of CG varied from metal to metal, but the order of Vo in the acidic pH region was Cu (II) > Fe (III) > Ni (II) > Zn (II) > Mn (II), Mg (II), Ca (II). Acid hydrolysis of CG in the absence of metals was negligible down to pH 1. The profiles of Vo of CS were similar to that of acid hydrolysis in the absence of metals, except for the Cu (II) system, which gave a higher Vo. Under the condition [substrate] : [Cu (II)] : [ligand]=1 : 10 : 10, the hydrolysis in the presence of various ligands was a pseudo-first order reaction (rate constant=k'). All ligands which coordinate to Cu (II) reduced the value of k'. Such metals-catalyzed hydrolysis may be one of the mechanism of hydrolysis of C conjugates to produce C-metal chelates in vivo.