Ureases: quantum chemical calculations on cluster models.

Area of Science:

• Computational chemistry
• Biochemistry
• Enzyme catalysis

Background:

• Urease enzymes catalyze urea hydrolysis, a critical biological process.
• Understanding the active site of urease is essential for elucidating its catalytic mechanism.
• Dinickel complexes are proposed models for the active site of urease enzymes.

Purpose of the Study:

• To computationally investigate dinickel complexes relevant to urease-catalyzed urea hydrolysis.
• To gain insights into the structure, substrate binding, and catalytic mechanism of ureases.
• To characterize the electronic and magnetic properties of realistic urease active site models.

Main Methods:

• Density functional theory (DFT) using the B3LYP functional.
• Characterization of equilibrium geometry, electronic properties, magnetic properties, and energies.
• Modeling of realistic dinickel complexes mimicking the urease active site.

Main Results:

• The water bridge in crystallographic urease structures was identified as a hydroxide bridge, consistent with antiferromagnetic coupling.
• Monodentate and bidentate urea-bound complexes with favorable catalytic orientations were characterized.
• Two distinct reaction mechanisms were investigated, highlighting the roles of a bridging hydroxide and a Ni2-bound water molecule.

Conclusions:

• The study provides a detailed computational analysis of dinickel complexes in urease catalysis.
• The findings clarify the structural and electronic factors governing urea hydrolysis by ureases.
• The identified reaction mechanisms offer valuable insights for understanding enzyme function and designing catalysts.