The oxidation by bromine of a variety of thioethers including N-acetyl-DL-methionine, 5′-methylthioadenosine, and tetramethylene sulfide has been found to be an interesting model system for the study of oxidative phosphorylation. The product of the oxidation of N-acetyl-DLmethionine has been shown to be the corresponding sulfoxide. With anhydrous pyridine as solvent, a mixture of the tetrabutylammonium salts of adenosine monophosphate and inorganic phosphate, N-acetyl-DL-methionine, and Br2 in the ratio of 1:2:2:4 results in 8.2 and 11.9% of the adenosine monophosphate being converted into adenosine diphosphate and adenosine triphosphate, respectively. A complex mixture of condensed inorganic phosphates is also produced including pyrophosphate, tripolyphosphate, trimetaphosphate, and probably tetrapolyphosphate. In this system, more than 75 % of the phosphate reacts and 75 % of this can be hydrolyzed to inorganic phosphate when heated in 1 N H2SO4 at 100° for 15 min. Systems containing 5′-methylthioadenosine or tetramethylene sulfide as the thioether gave similar results. The rates of oxidation and phosphorylation are very rapid at room temperature; more than 50% of the adenosine diphosphate and adenosine triphosphate is formed in the first minute. In the absence of inorganic phosphate, 94 % of the adenylic acid is converted into forms inactive in an enzymatic assay for adenosine monophosphate of which approximately 40% is P1P2-diadenosine 5′-pyrophosphate. These findings are interpreted in terms of a mechanism involving phosphorylated sulfonium intermediates which can react with suitable acceptors to form high-energy compounds. The possibility that thioethers and/or nonheme iron proteins are involved in biological oxidative phosphorylation is discussed. © 1969, American Chemical Society. All rights reserved.
