UC Santa Barbara

Carbon disulfide is an environmental toxin, but there are suggestions in the literature that it may also have regulatory and/or therapeutic roles in mammalian physiology. Thiols or thiolates would be likely biological targets for an electrophile, such as CS₂, and in this context, the present study examines the dynamics of CS₂ reactions with various thiols (RSH) in physiologically relevant near-neutral aqueous media to form the respective trithiocarbonate anions (TTC^-, also known as "thioxanthate anions"). The rates of TTC^- formation are markedly pH-dependent, indicating that the reactive form of RSH is the conjugate base RS^-. The rates of the reverse reaction, that is, decay of TTC^- anions to release CS₂, is pH-independent, with rates roughly antiparallel to the basicities of the RS^- conjugate base. These observations indicate that the rate-limiting step of decay is simple CS₂ dissociation from RS^-, and according to microscopic reversibility, the transition state of TTC^- formation would be simple addition of the RS^- nucleophile to the CS₂ electrophile. At pH 7.4 and 37 °C, cysteine and glutathione react with CS₂ at a similar rate but the trithiocarbonate product undergoes a slow cyclization to give 2-thiothiazolidine-4-carboxylic acid. The potential biological relevance of these observations is briefly discussed.