Formation of High-Energy Phosphate Bonds Effected by Electron-Deficient Sulfides

Electron-deficient sulfides are postulated as intermediates in the formation of a phosphorylated sulfonium salt which has previously been suggested as the high energy phosphorylating intermediate of respiratory chain-linked oxidative phosphorylation. To test the ability of electron-deficient sulfides to effect phosphorylation of adenine nun the presence of orthophosphate, an aromatic sulfur cation radical and dication are used as models. Treatment of the tetra-M-butylammonium salts of adenosine 5′-monophosphate and orthophosphoric acid in anhydrous acetonitrile with thianthrene perchlorate in the molar ratio of 1:1:2 results in the rapid formation of adenosine 5′-diphosphate and triphosphate in a combined yield of 16% based on the amount of thianthrene perchlorate added or 52% yield, based on the amount of adenosine 5′-monophosphate consumed. The thianthrene perchlorate is converted to thianthrene and thianthrene sulfoxide. Similar reactions with 2,3,7,8-tetramethoxythianthrene diperchlorate in place of thianthrene perchlorate result in the rapid formation of adenosine 5′-diphosphate and triphosphate in a combined yield of 19% based on dication added or 73% yield based on adenosine 5′-monophosphate consumed. Evidence concerning the mechanisms of these reactions is presented and discussed as well as their biological significance. In particular, theoretical consideration of electron-deficient aliphatic sulfides as intermediates in oxidative phosphorylation is presented. A key suggestion is that the oxidation potential of aliphatic sulfides and the stability of aliphatic sulfur cation radicals and/or dications can be affected by neighboring group participation.