Ureases: Quantum Chemical Calculations on Cluster Models

Herein, we present results from a computational study of dinickel complexes that are relevant to
the catalytic hydrolysis of urea exerted by the urease enzymes. The B3LYP density functional is used to
characterize the equilibrium geometry, electronic and magnetic properties, and energies for a series of
realistic complexes modeling the active site of ureases. The analysis of the theoretical results gives new
insight into the structure, substrate binding, and catalytic mechanism. The water bridge between the two
Ni(II) ions observed in the crystallographic structures of the ureases was assigned to a hydroxide bridge
in agreement with the observed small antiferromagnetic coupling. Both monodentate and bidentate urea-bound complexes, in which urea had favorable orientations for catalysis, were characterized. Finally, two
reaction mechanisms were investigated starting from the monodetante and bidentate urea-bound complexes,
respectively. Both a Ni1···Ni2 bridging hydroxide and a Ni2-bound water molecule play crucial roles in the
two mechanisms.

本研究报道了与脲酶催化尿素水解反应相关的双核镍配合物的计算化学研究结果。本研究采用B3LYP密度泛函（B3LYP density functional）理论，对一系列模拟脲酶活性位点的真实配合物的平衡几何结构、电子性质、磁学性质以及能量特征进行了表征。对理论计算结果的分析为理解该类配合物的结构、底物结合方式与催化机制提供了全新认知。脲酶晶体结构中观测到的两个镍(II)离子间的水桥，被指认为氢氧根桥，这一结论与实验观测到的弱反铁磁耦合结果相符。本研究还表征了单齿配位与双齿配位的尿素结合配合物，其中尿素分子均处于利于催化反应的取向。最后，本研究分别以单齿配位尿素结合配合物与双齿配位尿素结合配合物为起始模型，探究了两种催化反应机制。在这两种机制中，Ni₁···Ni₂桥联氢氧根与结合于Ni₂的水分子均发挥了关键作用。