Chemical modeling of the active site reaction mechanisms of superoxide dismutase

Abstract

Computational work 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 models include semi-empirical, Hartree-Fock, density functional, and electron correlation contained in the Spartan Pro 2004 program suite. Standard free energies for most levels of theory for the reaction of 1395 ± 3 kcal/mol were compared favorably with calorimetric value of -403.56. 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 state complexes involved in concerted, two step and three step mechanisms catalyzed by Cu2+. The corresponding values of 17.5, 28, and 36 kcal/mol for Ea show an increase with the complexity of the mechanism. A simplified mimic of the active site was optimized by the density functional method and the geometry of it was in accord with that found by X-ray diffraction experiments of the crystal and calculations by the PAW method.