Explaining Urease Specificity Towards Nickel: A Re-Analysis of Its Proposed Mechanism

Urease is a binuclear metalloenzyme selective towards nickel, exhibiting a remarkable rate enhancement of the catalytic reaction. The accepted mechanism for urease describes the coordination of urea to both nickel centers in an O,N bridged mode, enabling the attack of the carbonyl by a bridged hydroxide present between the metallic centers. However, the substitution of nickel by other metals significantly reduces urease´s catalytic efficiency. The proposed mechanism cannot explain this difference in activity since it does not follow a rational nucleophilicity scale. After a careful analysis of the literature data on thermodynamics, kinetics, inhibition, and mutations, we verified that by analyzing the mechanism from a diffrent angle, another pathway is most likely occuring. This mechanism can explain urease´s selectivity towards nickel and all the data present in the literature, gathering amost a century of study about urease.

Explaining Urease Specificity Towards Nickel: A Re-Analysis of Its Proposed Mechanism

Urease is a binuclear metalloenzyme selective towards nickel, exhibiting a remarkable rate enhancement of the catalytic reaction. The accepted mechanism for urease describes the coordination of urea to both nickel centers in an O,N bridged mode, enabling the attack of the carbonyl by a bridged hydroxide present between the metallic centers. However, the substitution of nickel by other metals significantly reduces urease´s catalytic efficiency. The proposed mechanism cannot explain this difference in activity since it does not follow a rational nucleophilicity scale. After a careful analysis of the literature data on thermodynamics, kinetics, inhibition, and mutations, we verified that by analyzing the mechanism from a diffrent angle, another pathway is most likely occuring. This mechanism can explain urease´s selectivity towards nickel and all the data present in the literature, gathering amost a century of study about urease.

A Mixed-Valence Tetra-Nuclear Nickel Dithiolene Complex: Synthesis, Crystal Structure, and the Lability of Its Nickel Sulfur Bonds

In this study, by employing a common synthetic protocol, an unusual and unexpected tetra-nuclear nickel dithiolene complex was obtained. The synthesis of the [Ni4(ecpdt)6]2− dianion (ecpdt = (Z)-3-ethoxy-3-oxo-1-phenylprop-1-ene-1,2-bis-thiolate) with two K+ as counter ions was then intentionally reproduced. The formation of this specific complex is attributed to the distinct dithiolene precursor used and the combination with the then coordinated counter ion in the molecular solid-state structure, as determined by X-ray diffraction. K2[Ni4(ecpdt)6] was further characterized by ESI-MS, FT-IR, UV-Vis, and cyclic voltammetry. The tetra-nuclear complex was found to have an uncommon geometry arising from the combination of four nickel centers and six dithiolene ligands. In the center of the arrangement, suspiciously long Ni–S distances were found, suggesting that the tetrameric structure can be easily split into two identical dimeric fragments or two distinct groups of monomeric fragments, for instance, upon dissolving. A proposed variable magnetism in the solid-state and in solution due to the postulated dissociation was confirmed. The Ni–S bonds of the “inner” and “outer” nickel centers differed concurrently with their coordination geometries. This observation also correlates with the fact that the complex bears two anionic charges requiring the four nickel centers to be present in two distinct oxidation states (2 × +2 and 2 × +3), i.e., to be hetero-valent. The different coordination geometries observed, together with the magnetic investigation, allowed the square planar “outer” geometry to be assigned to d8 centers, i.e., Ni2+, while the Ni3+ centers (d7) were in a square pyramidal geometry with longer Ni–S distances due to the increased number of donor atoms and interactions.

Di-μ-chlorido-bis[(2,2′-bipyridine-κ2N,N′)chlorido(N,N-dimethylformamide-κO)nickel(II)]

The title compound, [Ni2Cl2(μ-Cl)2(C10H8N2)2(C3H7NO)2], exists as a centrosymmetric dimer of two octahedral nickel centers. In the crystal, two chloride ions bridge the two nickel centers with one terminal chloride ion bound to each nickel atom. Coupled with a chelating bipyridine ligand and an O-boundN,N-dimethylformamide solvent molecule, each nickel center exhibits an slightly distorted octahedral coordination environment. The meridional chloride ions all sit in equatorial positions, with the bipyridine ligand occupying one equatorial and one axial position, and theN,N-dimethylformamide ligand occupying the final axial position. The 2,2′-bipyridine ligand binds to nickel in a near planar fashion, with the non-H atoms possessing a mean devation from planarity of 0.046 Å. No π–π interactions are observed in the crystal.