Chemistry of Metal -Bound Cysteine with Singlet Oxygen

We have been investigating mechanistic issues surrounding fundamental questions concerning the mechanism, potential reaction pathways, and susceptibility of cysteine ligands toward oxidation. Countless metalloenzymes contain one or several cysteine ligands at their active site, and oxidation of such metal-bound cysteine ligands may deactivate the enzyme. Some fundamental questions we seek to answer: How susceptible to oxidation are metal bound cysteine ligands? What factors (i.e. type and oxidation state of the metal, availability of coordination sites, etc.) control this reactivity? What are the products of such reactions, how is the product distribution affected by changes in the metal, the charge, the number of thiolates, presence of proton donors etc. in the binding site; do the products remain coordinated to the metal; and what are the biological consequences of the above?

We have found that singlet oxygen reacts with several Cobalt(III) thiolato complexes such as [(Co(en)₂(S-Cys)]²⁺ (BF₄)^- in water or methanol/water to give the corresponding sulfenato product. The rate of disappearance of the cobalt complex is twice the total rate of disappearance of singlet oxygen, indicating that upon attack on the thiolate moiety, all of the peroxidic intermediate goes on to form the sulfenato product. This implies that there is no physical quenching of singlet oxygen.

Possible mechanistic pathways are outlined below.

To study the effects of H-bonding (obviously very common in biological systems) on the reactivity of metal-bound cysteine complexes, we have prepared several Co(III) thiolato complexes that are soluble both in water/methanol and polar aprotic solvents such as DMF and acetonitrile. Rates of singlet oxygen disappearence as well as product formation will be measured in different solvent systems. We are also studying mononuclear and binuclear Ir(I) and Rh(I) thiolato complexes where oxidation of the metal and/or the thiolate is possible. Two unusual peroxo thiolato complexes have been characterized by x-ray molecular crystallography, in collaboration with Prof. R. Bau, director of the x-ray facility at the University of Southern California.