The Use Of Thiol Click Chemistry In Polymer Synthesis

Thiol click chemistry has many applications in organic synthesis,the preparation of macromolecules,materials science,nanomedicine and biomaterials due to its high efficiency,and selectivity.Here,we synthesize some sequence-controlled macromolecules,and some stimuli-responsive functional monomers macromolecules for gene and drug delivery.1.Sequence-ordered polymers were prepared by sequential Michael addition-based thiol-ene and free radical mediated thiol-ene reactions.The ring-opening of thiolactone produced thiolin situ,which can readily react with the electron-deficient carbon-carbon doublebond of allyl methacrylate via Michael addition-based thiol-ene,but can not react with theelectron-rich carbon-carbon double bond of allyl methacrylate without radicals,Subsequently,the in situ formed thiol was activated by UV irradiation,reacted with the electron-rich carbon-carbon double bond via a free radical-mediated thiol-ene reaction,and sequence-ordered polymers with high molecular weight formed.2.Sequence-ordered polymers were prepared by the combination of the thiol-ene click reaction and amine-yne click reaction.Due to the high selectivity of the reactions of amine and thiol with different groups(thiolactone,methacrylate,propiolate),the sequence of the produced polymer can be controlled simplely via sequential addition of monomers.All reactions involved in the polymerization were proceeded under mild condition without any catalyst and with 100%atom efficiency in one pot.Two kinds of DABCBA-sequenced copolymer were obtained.The NMR and GPC results confirmed the formation of polymers with high molecular weight.Moreover,by this method,redox-responsive disulfide bondscan be easily incorporated into the polymer chain,and the obtained polymer is bioreducible.3.Polycations have high DNA condensing ability,low immunogenicity,and great adaptability,which make thempromising for gene delivery.However,low transfection efficiency and inevitable toxicity are challenges ofcationic polymers.Here,we prepared poly(thioether)dendrimer,which was further conjugated with branched PEI viaMichael addition reaction,forming a novel amphiphilic Janus dendritic polymer.Theamphiphilic dendritic polymer can self-assemble into stable nanomicelles with high surface charge potential(+91.8 mV),which can be used as a gene delivery vector,exhibiting a higher genetransfection efficiency and much lower cytotoxicity.4.pH-sensitive zwitterionic coating molecules have been obtained.The pH-responsive zwitterionic molecules were capable of switching from "zwitterionic"at basic pH to "cationic" at acidic pH,which may in principle be "ideal" stealth coating materials that endow nanoparticles with both long systemic circulation and enhanced "stickiness" within tumors in vivo.The gold nanocage(AuNC)with pH-responsive zwitterionic shellsystematically achieved significantly enhanced accumulation within tumor and leaded to significantly improved therapeutic efficacy,as demonstrated with mouse models.