On Some Practical Aspects of Click Thiol-Ene Reactions for Polymer Modification and Conjugation with Biomolecules (Published)
Thiol-ene reactions are among the most popular click reactions, being particularly appealing for functionalization of polymer materials and conjugation with proteins. However, although the formal definition of “click chemistry” can be very strict, one can easily arise some controversial issues related to the application of thiol-ene reactions in actual process conditions. In order to illustrate some of these issues, thiol-ene reactions were performed at conditions that simulate the conjugation of proteins with unsaturated polymers. It is shown that the presence of a heterogeneous reacting system can exert enormous impact on the performance of thiol-ene reactions, which has been largely overlooked in the literature. It is also shown that the performance of heterogeneous click reactions depends on the many constituents of the reacting system so that the design of click reactions requires detailed analysis of the desired reaction system and may not necessarily constitute a mechanistic route for immediate bioconjugation applications.