Interaction of Urea with a Hydroxide-Bridged Dinuclear Nickel Center: An Alternative Model for the Mechanism of Urease

A hydroxide-bridged dinuclear nickel complex with a urea molecule linking the two metal ions
through its carbonyl oxygen atom has been prepared as a model for the metalloenzyme urease. This complex,
[Ni2(μ-OH)(μ-urea)(bdptz)(urea)(CH3CN)](ClO4)3, where bdptz is the dinucleating ligand 1,4-bis(2,2‘-dipyridylmethyl)phthalazine, effects the hydrolysis of urea upon heating in a two-step reaction. In the first
step, a molecule of ammonia is eliminated from urea with concomitant production of cyanate, the first-order
rate constant in acetonitrile being (7.7 ± 0.5) × 10-4 h-1. This reaction is at least 500 times faster than the
spontaneous decomposition of urea under the same conditions. When the cyanate-containing product is further
heated in the presence of water, the cyanate is hydrolyzed with a second-order rate constant of (9.5 ± 1) ×
10-4 M-1 h-1. Reaction of [Ni2(μ-OH)(μ-urea)(bdptz)(urea)(CH3CN)](ClO4)3 in 50% aqueous acetonitrile
afforded ammonia with no appreciable buildup of the cyanate-containing species. A possible analogue of the
cyanate-containing product, [Ni2(μ-OH)(μ-H2O)(bdptz)(μ-OCN)]2(OTs)4, was independently synthesized and
structurally characterized. These results establish the precedence for hydrolysis of urea via a cyanate intermediate
as an alternative mechanism for the urease-catalyzed hydrolysis of urea.