Spin Transition during H2O2 Formation in the Oxidative Half-Reaction of Copper Amine Oxidases

• Published in: The journal of physical chemistry. B 2004-09, Vol.108 (36), p.13882-13892
• Main Authors: Prabhakar, Rajeev, Siegbahn, Per E. M, Minaev, Boris F, Ågren, Hans
• Format: Article
• Language: English
• Subjects: activation; biogenesis; continuum dielectric theory; crystal-structure; dioxygen; enzyme catalysis; hansenula-polymorpha; mechanism; self-consistent-field; topaquinone
• ISSN: 1520-6106; 1520-5207; 1520-5207
• DOI: 10.1021/jp0478312

Dioxygen reduction in the oxidative half-reaction of copper amine oxidases (CAOs) has been studied quantum chemically using the hybrid density functional theory (B3LYP). The reductive activation of dioxygen is a spin-forbidden process for which substantial kinetic O-18 (but no deuterium) isotope effects have been found experimentally. The proposed mechanism was divided into three steps, and the last step was studied for two different potential energy surfaces:  the quartet and the doublet surfaces. It is suggested that dioxygen reduction occurs through a spin transition that is induced by the exchange interaction between the unpaired spins of the Cu(II) ion and the O2 - anion. The step involving this spin transition is suggested to be rate-limiting, which gives a rationalization for the puzzling experimental results when copper is substituted for other metals. The spin transition is triggered by the calculated vibronic perturbation of 5.4 (kcal/mol) Å-1, which leads to a very fast rate of 8 × 1010 s-1 for the spin transition. However, since the spin transition occurs at a calculated energy that is 18−20 kcal/mol higher than that of the reactant, this step could still be rate-limiting. The difference in the O−O bond distance between the resting state (free dioxygen) and the point of the spin transition provides an explanation for the oxygen isotope effect.