Computational Analysis of the Superoxide Dismutase Mimicry Exhibited by a Zinc(II) Complex with a Redox-Active Organic Ligand.

Previously, we found that a Zn(II) complex with the redox-active ligand N -(2,5-dihydroxybenzyl)- N , N ', N '-tris(2-pyridinylmethyl)-1,2-ethanediamine (H 2 qp1) was able to act as a functional mimic of superoxide dismutase, despite its lack of a redox-active transition metal. As the complex catalyzes the dismutation of superoxide to form O 2 and H 2 O 2 , the quinol in the ligand is believed to cycle between three oxidation states: quinol, quinoxyl radical, and para -quinone. Although the metal is not the redox partner, it nonetheless is essential to the reactivity since the free ligand by itself is inactive as a catalyst. In the present work, we primarily use calculations to probe the mechanism. The calculations support the inner-sphere decomposition of superoxide, suggest that the quinol/quinoxyl radical couple accounts for most of the catalysis, and elucidate the many roles that proton transfer between the zinc complexes and buffer has in the reactivity. Acid/base reactions involving the nonmetal-coordinating hydroxyl group on the quinol are predicted to be key to lowering the energy of the intermediates. We prepared a Zn(II) complex with N -(2-hydroxybenzyl)- N , N ', N '-tris(2-pyridinylmethyl)-1,2-ethanediamine (Hpp1) that lacks this functional group and found that it could not catalyze the dismutation of superoxide; this confirms the importance of the second, distal hydroxyl group of the quinol.