Synthesis And Degradation Regulation Of Poly(benzyl Ether)-based Self-immolative Polymers

Self-immolative polymers?SIPs?are a unique class of stimuli-responsive materials that typically consist of a thermodynamically unstable polymer backbone at room temperature and a reactive capping group that responds to expernal stimuli.Once the capping group of the polymer is removed,the polymer undergoes a caacade of entropy-driven electronic elimination process from head-to-tail,resulting in the irreversible,domino-like disintegration of the polymer into its building blocks.In the past decade,various types of dendritic and linear macromolecular SIP structures have been derived from self-immolative small molecules.SIPs have attracted considerable attention due to their unique stimuli-responsiveness and controllable degradation characteristics.From a synthetic perspective,more powerful approaches toward accessing SIPs via controlled chain growth polymerization mechanisms are highly desirable.Until now,only two kinds of SIP backbones,poly?phthalaldehyde??PPA?and poly?benzyl ether??PBE?,have been sunthesized by controlled chain growth polymerization mechanism.Among them,the synthesis conditions of PBE are relatively mild and simple,which are generally carried out at 0?or-20?.Moreover,the monomer and polymer structures are eaay to be chemically modified.However,there are few studies on the PBE-based self-immolative polymeric structures.The self-immolation rate of the PBE ssolution has been reported to be very fast,so the ability to modulate the depolymerization profile for a sing le type of monomer such that variation between rapid and prolonged depolymerization can be controlled is helpful for better exploring the influencing factors of the depolymerization process and addition systematic investigation of the relationship between monomer and depolymerization kinetics would be valuable for future SIP designs.In this article,the PBE structure with relatively mild and controllable polymerization conditions was chosen as the self-immolative polymer backbone.Starting from the design of monomer,a series of PBE-based self-immolative polymer structures such as linear polymers,brush-type polymers and organogels.Specific works are summarized as follows:?1?In order to expend the further functional ability of the PBE-based SIPs,we have synthesized the self-immolative backbone via anionic polymerization of an alkyne-modified quinone methide monomer.Two end-capping agents were used:tert-butyldimethysilyl chloride?TBSCl?and allyl chloroformate?ACF?,which form silyl ether and carbonate linkages with the growing phenolate chain-end,respectively.We have discussed the synthesis process of PBE backbone by studying the conditions of solvent and oxidant in the synthesis of quinone methide monomer and the influence of solvent and end-capping conditions during anionic polymerization.Then,we established methods for a grafting-onto synthesis of self-immolative brush polymers with different end-cap functionalities and side chains.Two types of azide-terminated polymers,polystyrene?N₃-PS?or polyethylene glycol?N₃-PEG?,are used as side chains to couple with the PBE-based self-immolative backbone via high-efficiency copper-catalyzed click chemistry.The kinetics of coupling reaction was monitored by gel permeation chromatography?GPC?with dimethylformamide?DMF?as eluent.The grafting efficiency was evaluated by comparison of the peak intergrations of the brush vs unreacted side chains,it is determined that the yield for PEG conjugation is nearly quantitative,while that for PS conjugation plateaus in the range of?70%.These results are corroborated by an alternative method for calculating grafting density using FTIR analysis of unreacted alkyne groups.?2?Through GPC with DMF or tetrahydrofuran?THF?as eluent,we demonstrated the regulation of self-immolation process of the PBE-based brush polymer with different responsive end-cap and different side chains synthesized in the previous chapter.Theoretically,upon exposure to a decapping reagent?Pd?0?or F^-?,these brush polymers undergo an irreversible degradation cascade?decapping and self-immolation?from head to tail to yield individual side chains.We studied the relationship between the PBE-based polymer structures and the regulation of self-immolation process.It is observed that several factors affect the depolymerization kinetics,including solvent polarity,type of counter ion,the rate of the decapping chemistry,and interestingly,the rigidity of the side chains.The rate of decapping will affect the rate of degradation but will not produce intermediate molecular weight?MW?polymers.The polarity of solvent has a great relationship with the remove rate of the counterion of phenolate anion which is directly related to whether the intermediate molecular weight?MW?polymers are generated during the self-immolation process,and thus affect the overall rate of depolymerization.The rigidity of the side chains will limit the rotational freedom the depolymerizing chain-end phenolate unit,which must reach a proper orbital alignment?coplanar?for elimination to occur.Through these series of studies,the PBE-based brush polymer synthesis and a fundamental understanding of their degradation characteristics pave the way for further chemical investigations as well as technological applications.?3?In addition to exploring the chain end induced self-immolative chemistry,we also discussed the side chain induced self-immolation based on PBE structure.Herein,we report a PBE-based SIP with pendant pyridine disulfide groups.Cleavage of the side-chain disulfides leads to the formation of phenolates,which initiate depolymerization from the side chain.Due to the higher density of the disulfide groups compared to that of the chain-end-capping group,which normally is responsible for initiating depolymerization of SIPs,the side chain-immolative polymer?ScIP?can be readily degraded in the solid state where the mobility of polymer chains is substantially limited.The ScIP was also further modified through the thiol-disulfide exchange reaction to prepare ScIP-g-PEG graft polymers and organogels,which were also able to undergo complete reductive self-immolative degradation.Morever,we modeled the cleavage of the disulfides as a stochastic event and predicted the molecular weight distributions of the degraded ScIP as a function of%disulfide cleaved.The simulation nicely matches those observed with GPC,corroborating the proposed degradation mechanism.?3?In order to expand the molecular amplification characteristics of PBE-based self-immolative polymer,we designed and synthesized an azide-functionalized quinone methide monomer and.The PBE with azide group as side chain?AZP?was synthesized by the“two-step initiation”anionic polymerization.We demonstrated the responsiveness of AZP polymer to Na₂S and H₂S by NMR and GPC,respectively.It was found that the phenomenon is quite strange which the Na₂S solution can promote the azide side chain of AZP polymer to become amino group and then trigger the side chain induced self-immolation process while the H₂S gas in the organic phase can not promote the degradation of the polymer,but induce its molecular weight increase.For the difference between these two response,we proposed the corresponding mechanism hypothesis.In addition,we monitored the change of absorption spectrum of AZP polymer in response to H₂S gas by UV-vis spectrophotometer.The feasibility experiment of H₂S gas detection was carried out.It was found that the sensitivity of AZP polymer to H₂S can be improved by adding DBU.