Synthesis of a Cysteine Diels–Alder-based Polymer by Simultaneous Double-Click Chemistry and Its Cyto-Genotoxicity Evaluation

The click chemistry reactions and its use in living organisms have been widely developed; however, few studies describe the safety of the reagents and products. Furan–maleimide represent one important pair of reagents for the click Diels–Alder reaction, and were chosen here to perform the minimalist click reaction with cysteine to reveal their preliminary safety features by cytotoxicity tests. The functional groups of amino acids allow them to be chemically modified, mainly for the synthesis of monomers and polymers. Here, cysteine was used in the click reaction, since it displays an SH group in its side chain, useful to perform thiol–ene reactions. Its amine group easily reacts with anhydrides, allowing it to couple with the furan derivative “furan–maleic anhydride adduct”. The mixture of the cysteine with the adduct in solution gives rise to the double simultaneous thiol–ene/amine maleimide click reactions. The thiol group and the furan double bond provide the reactive functional groups for the polymerization. The synthesis of the polymer based on cysteine–Diels–Alder adduct confirmed the condensation nature of the reaction. Preliminary safety and biocompatibility tests of this new polymer and its starting reagents were carried out, since these parameters represent one of the most important features for operating and scaling up the production. This one-step double-click reaction is interesting for application in several fields, since it has the advantage of using natural and renewable raw materials, in addition to its handling safety. Furan–maleic anhydride adduct and cysteine forming a new Diels–Alder-based polymer Cysteine reacts in a double-click reaction with furan–maleic anhydride adduct. The simultaneous reactions give rise to a cysteine-based polymer. Cytotoxicity tests indicated the safety of all the reagents and products. Mutagenicity tests indicated the safety of the polymer for conventional uses.