Amide Hydrolysis Effected by a Hydroxo-Bridged Dinickel(II) Complex:  Insights into the Mechanism of Urease

Abstract

A series of dinuclear nickel complexes, [Ni 2 (H 2 O) 4 (bdptz)](OTs) 4, [Ni 2 (OH)(H 2 O) 3 (bdptz)](OTs) 3, and [Ni 2 (H 2 O)(OH) 2 (bdptz)] 2 (OTs) 4, where bdptz is the dinucleating ligand 1,4-bis(2,2‘-dipyridylmethyl)phthalazine and OTs is p -toluenesulfonate, were prepared as models for urease. Potentiometric titration of [Ni 2 (H 2 O) 4 (bdptz)](OTs) 4 revealed two deprotonation constants with p K a values of 4.38 ± 0.02 and 8.51 ± 0.02. The product of the first deprotonation, [Ni 2 (OH)(H 2 O) 3 (bdptz)](OTs) 3, effected the stoichiometric hydrolysis of picolinamide in ethanol, a heretofore unprecedented transformation in a dinuclear metallohydrolase model complex. Picolinamide hydrolysis by [Ni 2 (H 2 O) 4 (bdptz)](OTs) 4 or [Ni(terpy)(H 2 O) 3 ](OTs) 2 (terpy = 2,2‘:6‘,2‘ ‘-terpyridine) under the same conditions was not observed. This amide hydrolysis mimics the hydrolysis of urea by the metalloenzyme urease in that a hydroxide nucleophile is produced by the dinuclear metal center and the amide is activated for nucleophilic attack by coordination to the dinuclear nickel center.