A Study of the Equilibrium and Kinetics of Urea Binding by a Biomimetic Dinickel(II) Complex

Abstract

AbstractThe equilibrium and kinetics of urea binding by model dinickel complexes have been studied, which is relevant to the activity of the urease enzyme. The pyrazolate‐based, O2H3‐bridged dinuclear nickel(II) complex [LNi2(OH)(H2O)]2+ (1) binds urea reversibly in organic solvents with the formation of an N,O‐bridged urea anion complex [LNi2[OC(NH2)NH)]2+ (2) and two water molecules. The equilibrium constant has been measured as 4.3(4) in acetone, 2.7(5) in acetonitrile, and 3(1) in methanol at 25 °C. Upon dissolving 1 in anhydrous methanol, the O2H3 bridge is substituted for an O2Me2H bridge to give [LNi2(OMe)(MeOH)]2+ (4),which has been crystallized as 4·(ClO4)2 and characterized by X‐ray diffraction. Both NiII ions in 4 are five‐coordinate with geometries intermediate between square‐pyramidal and trigonal‐bipyramidal. The H atom in the Me2O2H bridging unit is located in an asymmetric position. The exchange of water and methanol ligands in complexes 1 and 4 is very fast in solution at 25 °C (kobsd. > 103 s−1). Binding of urea by complexes 1 and 4 are slower reactions (kobsd. ≈︁ 10−1 to 101 s−1 under the concentration conditions used) and can be monitored by stopped‐flow techniques. Detailed kinetic studies indicate that binding of urea is a multi‐step process. Steady‐state intermediates of the tentative formula [LNi2(OR)(urea)n]2+ (n = 1, 2) are formed in fast preequilibrium with the starting complexes 1 (R = H) and 4 (H = Me), respectively. The bidentate N,O‐coordination and deprotonation of an O‐bound urea ligand constitute the overall rate‐limiting step. The kinetic data suggest that both mono‐ and bis(urea) complexes participate in the formation of the chelate 2, and that the latter are substantially more reactive. The bis(urea) pathway was unexpected because only one urea molecule is incorporated into the final product 2. Reactive intermediates [LNi2(OH)(urea)n]2+ are close analogs of the reactive intermediate of urease, which also has the hydroxide and urea ligands bound at a dinickel core. However, the reactivities of the intermediates are different. The hydroxide ligand in our model complex acts as a base towards urea, and the urea anion complex 2 is formed. In urease, the hydroxide ligand attacks urea as a nucleophile leading to the hydrolysis of urea. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)