Transthiolation

Transthiolation is a chemical reaction in which a thiol or thiyl group is transferred from one sulfur-containing molecule to another, effectively exchanging sulfur-containing moieties between substrates. In practice this often involves a thiolate attacking a disulfide bond, generating a new disulfide and a liberated thiolate, or a thiol exchanging with a disulfide to yield a different disulfide and a free thiol. A common way to describe the process is: R-S− + R'-S-S-R'' → R-S-S-R'' + R'-S−, which can be protonated to form R'-SH, illustrating the reversible nature of the exchange.

Biological relevance is tied to thiol-disulfide exchange processes that regulate protein redox state and activity. Enzymes such as thioredoxin, glutaredoxin, and protein disulfide isomerase catalyze transthioolation and related exchanges in cells, contributing to redox signaling, folding of disulfide-rich proteins, and defense against oxidative stress. Mixed disulfides formed during transthioolation, such as protein–SSG (glutathionylation) or protein–SSR species, can be resolved to alter function or to transmit redox information.

In addition to biology, transthioolation is utilized in biochemistry and protein engineering to rearrange disulfide bonds, modify thiol content, or study redox-dependent conformational changes. It is also a component of dynamic covalent chemistry approaches that exploit thiol-disulfide exchange to create reversible, stimulus-responsive systems. Overall, transthioolation describes the flexible and reversible transfer of sulfur-containing groups between sulfur-containing substrates.