The Preparation And Characterisation Of Thermoresponsive Hydrogels Based On DIELS-ALDER Reaction

Hydrogels are widely used in biomaterials and pharmaceutical industry such as contact lenses, biosensor, biological membranes, artificial organs and drug delivery systems, due to their typical characteristics. Their properties and applications are greatly influenced by the means and conditions to prepare them. Based on the properties of the Diels-Alder reaction, it can be speculated that Diels-Alder reaction is a promising and ideal reaction for the preparation of hydrogels.Firstly, three diene-functionalized bipolymers poly (DMA-co-FM), poly(VP-co-FM) and poly(NIPA-co-FM) were synthesized by free radical copolymerization of furfuryl methacrylate(FM) with N, N-dimethylacrylamide(DMA), N-vinyl-2-pyrrolidone(VP) and N-isopropylacrylamide(NIPA) respectively, with 2, 2'-azobisisobutyronitrile(AIBN) as an initiator. In the same way, diene-functionalized terpolymer poly (NIPA-co-DMA -co-FM) was also prepared by free radical copolymerization of NIPA, DMA and FM.Secondly, N-4-(carboxyl) phenyl maleimide (p-CPMI), N-maleoyl alanine (AMI) and N-maleoyl-L-leucine (LMI) were synthesized by maleic anhydride with p-aminobenzoic acid, L-alanine and L-leucine respectively. N-4-(Chlorocarbonyl) phenyl maleimide (p-CPMIC) was prepared by further reaction of p-CPMI with thionyl chloride. Then, dienophile-functionalized polymers PEG-DMI, PEG-AMI and PEG-LMI were prepared by reacting poly (ethylene glycol) 2000 (PEG) with p-CPMIC, AMI and LMI respectively. In addidion, dienophile-functionalized terpolymer poly (NIPA-co-DMA-co-HEMA)-AMI was synthesized by the reaction of AMI and the as-prepared terpolymer Poly (NIPA-co-DMA-co-HEMA). At last, four novel thermosensitive hydrogels were prepared by aqueous Diels-Alder reaction of poly (DMA-co-FM) and PEG-DMI, poly (VP-co-FM) and PEG-AMI, poly (NIPA-co-FM) and PEG-LMI, poly (NIPA -co- DMA -co-FM) and poly (NIPA-co-DMA-co-HEMA)-AMI respectively. The samples obtained at different steps were characterized by UV, IR, NMR, GPC, SEM, CD, etc.It was found that LCST of copolymers decreases with the increase of FM content in copolymers, and increases with the increase of DMA content in copolymers. Both the DA reaction and retro- DA reaction were closely related to the temperature and the solvents used. The rate of DA reaction and retro- DA reaction were both increased with the increase of the temperature. The hydrogels are of high stability in water, and water can accelerate the Diels–Alder reaction, whereas the organic solvents with bigger polarity (DMF, DMSO) could accelerate the retro-Diels–Alder reaction. The swelling behavior study by gravimetric measurement indicates that the hydrogels possess thermoresponsivity and exhibit considerable swelling ratio in water.In conclusion, the thermosensitive hydrogels were prepared by means of clean and efficient DA reaction in water. The preparation process is facile and the reaction conditions are mild with neither initiator nor organic solvent. The gelation time can be controlled by temperature and the component of copolymer. The method presented here has potential applications in the preparations of hydrogels and biomaterials.