Studies of Biologically Relevant Oxidation Processes with Singlet Oxygen

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DESCRIPTION (provided by applicant): The chemistry of singlet oxygen with metal-bound thiolates, arylphosphines and some phenolic antioxidants will be explored. Very little research has been accomplished in this area. The basic aims are twofold (i) To solve a number of fundamental mechanistic questions in oxidation chemistry, especially concerning the reactivity of peroxidic intermediates formed during oxidations initiated by so-called "reactive oxygen species" and (ii) to explore chemistry of singlet oxygen - a highly reactive oxygen species - with seleced biomolecules. Reactive intermediates in oxygen chemistry are often difficult to detect because they themselves are powerful oxidants. We are using singlet dioxygen to observe and possibly isolate such species and, where applicable, to investigate their potential as oxidants. Specifically, the chemistry of singlet oxygen with metal thiolates, especially S-bound cysteine, will be investigated. We will explore the diverse reaction pathways such as formation of sulfenate, sulfinate, C-S bond cleavage or oxidative addition at the metal center. We will determine factors (oxidation state of metal, protic vs. aprotic environment, sterics) that determine the susceptibility of such thiolates toward oxidative damage. Thiolate ligands often serve as bridges in multinuclear complexes, and the chemistry of such species with singlet oxygen will be explored as well. Both ligand oxidation and reaction of dioxygen at the metal center are possible reactive pathways in such systems. We will address the fundamental question of how oxidation at the first metal affects reactivity at the second metal center. We will also investigate the chemistry of other unusual peroxides. We are planning to study the chemistry of phosphadioxiranes, as an example of a highly reactive heteroatom peroxide. This species acts as an "oxene"-like oxygen atom transfer agent, and undergoes several other reactions discovered by us. We will study the factors that govern the reactivity of this highly unstable reactive intermediate. Finally, we will study the chemistry of the powerful phenolic antioxidant trans-resveratrol with singlet oxygen. The chemistry of resveratrol with free radicals is well known. However, its chemistry with singlet oxygen has not been explored, yet knowing whether or not resveratrol forms highly reactive peroxidic species with singlet oxygen is essential to evaluate its health benefits. We will determine the products and any reactive intermediates formed during the interaction between resveratrol and singlet oxygen.