Sunlight-Mediated Thiol-Ene/Yne Click Reaction: Synthesis and DNA Transfection Efficiency of New Cationic Lipids

Abstract

The design of green synthetic reaction conditions is very challenging, especially for biomaterials, but worthwhile if the compounds can be easily synthesized in the aqueous medium. Herein, we report the development of sunlight-mediated thiol-ene/yne click reaction in the presence of a catalytic amount of tert-butyl hydroperoxide (TBHP) in an aqueous medium. The optimized reaction conditions were successfully applied to synthesize a series of small molecules and lipids in a single step in the aqueous medium. The synthetic cationic lipid/co-lipid formed positively charged stable nanosized liposomes that effectually bind with the genetic materials. The in vitro DNA transfection and cellular uptake assays showed that the synthesized cationic lipids have comparable efficiency to commercially available Lipofectamine 2000. This mild synthetic strategy can also be used for smart design of novel or improvement of prevailing lipid-based nonviral gene delivery systems. Such chemical transformations in the aqueous medium are more environment-friendly than other reported thiol-ene/yne click reactions performed in an organic solvent medium.