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, [Ni-2(mu-OH)(mu-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) x 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) x 10(-4) M-1 h(-1). Reaction of [Ni-2(mu-OH)(mu-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, [Ni-2(mu-OH)(mu-H2O)(bdptz)(mu-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.