Theoretical study on the inhibition mechanisms of heavy metal ions on urease activity

Soil urease is highly sensitive to soil heavy metal pollution, and thus its activity can be used as bio-indicator of soil health. However, little is known about the inhibition mechanisms of heavy metals on urease. The effects of dimetallic substitution (i.e., Cd, Co, Cu, Hg, and Zn) on the binding of urea in the urease and its subsequent decomposition were studied using quantum chemical methodologies with a urease mimic (phthalazine-dinickel complex). The dimetallic substitution altered the structural features of the dimetal complexes and the M−O bond length between the dimetals and the carbonyl-O of coordinated urea molecules, weakening the binding energies of urea in dimetal complexes, which further affected the transformation of urea. In the urea decomposition via intra-molecular proton transfer, all dimetal complexes have a high activation barrier due to the weak binding of urea in complexes and hydrogen bonding within urea molecules, which are therefore difficult to occur spontaneously. In the urea decomposition via water-assisted inter-molecular proton transfer, the addition of water molecules decreased the energy barrier of urea decomposition. Regardless of the urea decomposition pathway, the dimetallic substitution altered the M−O bond length and hydrogen bond pattern of intermediates and transition states, and also affected the leave of the resulting NH3 from the dimetal complexes by regulating the C–N bond length within the decomposed urea molecule. Overall, the theoretical study provided insight into the molecular mechanisms of the inhibitory effects of heavy metals on urease activity. © 2023 Elsevier Ltd