New Thiol-Based Reactions

In 2004, Ramstrom and coworkers reported the first prototype DCLs based on a reversible transthioesterification reaction [47]. DCLs of potentially ten different thioesters were generated from a series of five thioesters - all prepared from 3-sulfanylpropionic acid - and one thiol (thiocholine). Transthioesterification (exchange) reactions were observed by simply mixing the different DCL components in aqueous solution. Interestingly, when added to the equilibrated mixture of thioesters, the enzyme acetylcholinesterase was able to recognize and subsequently hydrolyze its best substrate selectively. This selective hydrolysis 

In 2005, the Michael addition of thiols to enones was added to the list of reversible reactions compatible with the concept of DCC (Fig. 6d). Shi and Greaney investigated the reactivity of glutathione (GSH) toward a series of ethacrynic acid (EA) derivatives in a mixture of DMSO and water at pH 8 [51]. A DCL of six GSH-EA derivatives, products of the Michael addition, was generated which proved responsive to changes in pH. Thermodynamic equilibrium was typically attained after 3 h. Acidification to pH 4 has the immediate effect of switching off the Michael addition and therefore represents a practical way to freeze the equilibrium before analyzing the composition of the DCL. 

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