Multicomponent Synthesis Of Polyrotaxane-structured Glycopolymers And Their Bio-applications

Glycopolymers are functional materials with saccharide groups pendant to the main polymer chain,which can enhance valence binding activities due to the multivalent saccharide ligands as a result of cluster glycoside effect.Glycopolymers have wide applications such as targeted drug delivery,biosensors and protein purification due to the specificity of interaction between sugars and cell surface receptor proteins(lectins).Compared with homoglycopolymers,which contain only a single type of sugar residue,increasing attention has been drawn to heteroglycopolymers consisting of a variety of sugar residues whose heterogeneity is used to enhance affinity and selectivity towards a specific receptor.Glycopolymers can be synthesized generally either via polymerization of sugar monomers or by post-functionalization of sugar moieties with a preformed polymer.However,a number of these sugar monomers tend to self-polymerize.Post-functionalization,especially multicomponent reaction,has aroused interests because it is much easier to control and has more variability.Usually,post-functionalization needs several reaction steps.A one-pot method with high conversion rate will be much more convenient and highly recommended.Based on the above research,we introduce one-pot method to prepare polyrotaxane(PR)-based heteroglycopolymers,which armored with different sugar and fluorescent moieties,via the combination of host-guest interaction,thiol-ene and copper catalyzed click chemistry in water.Specifically,thiol-ene and copper-catalyzed click reactions on ?-CDs were achieved in “one pot” in water with rapid speed,and then ?-CDs with sugars are threaded on linear chain PPG,like a necklace,through host-guest interaction.Compared with traditional heteroglycopolymer,?-CDs with well-defined pendent sugars can rotate and move along a linear chain PPG in the PR--the characteristic of polyrotaxanes,which enhances interactions with biomacromolecules such as receptor proteins on the cell membrane.Therefore,my work can be divided into three parts:(1)Modular preparation of polyrotaxane-based glycopolymers and their research on bacteria-specific captureWe have successfully prepared polyrotaxane-based glycopolymers with sugar units on the side chains through the host-guest interaction and the click reaction in water.The successful synthesis of polyrotaxane-based glycopolymers was verified by FT-IR,NMR,X-ray diffraction and GPC.Mannose and glucose-regulated pseudopolyrotaxanes were successfully prepared by adjusting the ratio of alkynyl mannose to acrylamide-based glucose during synthesis process.At the same time,we also introduced mono-substituted ?-CD-Rhodamine onto polyrotaxane to verify its ability to bind to lectins and bacteria.Polyrotaxane with mannose component has stronger binding ability to Con A and bacteria,and polyrotaxane possessing both mannose and glucose units has better binding ability,which may be due to "sugar cluster effect ".(2)Preparation of antibacterial polyrotaxane-based glycopolymers and their antibacterial propertiesWe formed polyrotaxane-based glycopolymers in a one-pot reaction by click reaction as well as the host-guest interaction.Through NMR,FT-IR,XRD tests proved that we have successfully prepared the glycopolymers.It was finally proved by plate coating method that the prepared polyrotaxane had good bactericidal performance and the minimum inhibitory concentration was found out.The cytotoxicity test finally found that the polyrotaxane containing mannose and the quaternary ammonium salt possesses relatively good biocompatibility and has the best compatibility.Similarly,the final co-culture experiment also demonstrated that the polyrotaxane containing mannose and quaternary ammonium salts had lower toxicity during bacterial cell co-culture and was effective as bacteriostasis.Finally,polyrotaxane-based bactericidal substances are formed in a one-pot reaction by means of click-reaction and host-guest action,and the bactericidal substance has good bactericidal properties and low biological toxicity.(3)Preparation of polyrotaxane glycosaminoglycan analogues and their anticoagulant studyWe finally prepared polyrotaxane glycosaminoglycan analogs by the host-guest interaction and the one-pot synthesis,and confirmed the successful synthesis of such a glycosaminoglycan analog by means of NMR and FT-IR.The anticoagulant properties of the polyrotaxane-containing sugar-containing polymer were also demonstrated by the plasma re-calcification test and the final result showed that the polyrotaxane containing ?-CD-sulfonic acid possessed good anticoagulant properties and whether polyrotaxane was enclosed endothelium has little effect on the anticoagulant properties.