Computational Evaluation of Mechanistic Pathways of Action of Superoxide Dismutase

Abstract

Computational studies on thermodynamics of dismutation of superoxide anion radicals (O₂-) to hydrogen peroxide and molecular oxygen was conducted with various theoretical models using a variety of basis sets. The computational models include semi-empirical, Hartree-Fock and density functional contained in the Spartan 2004* program suite. The catalytic role of Cu²⁺ in the superoxide dismutase enzyme was reflected by observing its effect on reducing the activation energies. Activation energies were computed for various transition states complex involved in concerted, two step and three step mechanisms catalyzed by [Cu(NH₃)₄(H₂O)₂]²⁺. Based on this analysis, mechanisms which include the peroxy radical (.OOH) are less favored than those which include neutral O₂ in a transition state complex, or involve both H⁺ donors and a superoxide (O₂₋) in a single step.