Interaction of urea with a hydroxide-bridged dinuclear nickel center: An alternative model for the mechanism of urease
Interaction of urea with a hydroxide-bridged dinuclear nickel center: An alternative model for the mechanism of urease
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DOI：
10.1021/ja000202v
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发表时间：
2000-09-27
影响因子：
15
通讯作者：
Lippard, SJ
中科院分区：
文献类型：
--
作者：
Barrios, AM;Lippard, SJ
已经制备了一种氢氧化物桥联的双核镍络合物，其具有通过其羰基氧原子连接两个金属离子的脲分子，作为金属酶脲酶的模型。该配合物 [Ni-2(mu-OH)(mu-urea)(bdptz)(urea) (CH3CN)](ClO4)(3)（其中 bdptz 是双核配体 1,4-双（2,2'-联吡啶甲基）酞嗪）在两步反应中加热时实现尿素水解。第一步，从尿素中消除一个氨分子，同时产生氰酸盐，乙腈中的一级速率常数为(7.7+/-0.5)×10(-4)h(-1)。该反应比相同条件下尿素的自发分解至少快500倍。当含氰酸盐产物在水存在下进一步加热时，氰酸盐以(9.5+/-1)×10(-4)M-1h(-1)的二级速率常数水解。 [Ni-2(mu-OH)(mu-尿素)(bdptz)(尿素)(CH3CN)](ClO4)(3)在50%乙腈水溶液中反应得到氨，而没有明显的含氰酸盐物质的积累。独立合成了含氰酸盐产物的可能类似物[Ni-2(mu-OH)(mu-H2O)(bdptz)(mu-OCN)](2)(OTs)(4)并进行了结构表征。这些结果确立了通过氰酸酯中间体水解尿素作为脲酶催化尿素水解的替代机制的优先性。
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.