Preparation And Chiral Recognition Of Chiral Copolymers Based On L-leucine Monomer

Chiral recognition is of great significance in the fields of life sciences and medicinal chemistry.Among chiral identification materials,amino acids have been widely used due to their advantages of being inexpensive,easy to prepare,stable in nature,and good chiral separation ability.At the present stage,most amino acid modified monomers contain both ester and amide groups,and the chiral recognition ability of the amide group is better than the ester group,so it is beneficial to enhance the recognition ability by converting the ester group into amide group.I n addition,there are few reports of chiral recognition using amphiphilic copolymers with amino acids as chiral centers.Therefore,In this project,the chiral monomers containing two amide groups were synthesized,then two amphiphilic copolymers and two c hiral silica gels were prepared.the structure and properties of each product were characterized,and the chiral recognition of chiral polymers was studied.The specific contents are as follows:?1?The N-methylacryl-L-leucyl methylamine?MALMA?monomer was successfully synthesized by using L-leucine as raw material.Polyethylene glycol monomethyl ether acrylate?MPEGAA?was prepared.Amphiphilic copolymers are synthesized by radical polymerization of MALMA and MPEGAA,and micellar solution is also prepared.The drug-loading capacity and selective release properties of copolymer micelles were studied.FT-IR,¹H NMR,GPC,TEM,polarimeter and UV spectrophotometer results show that:Monomer and amphiphilic copolymers were successfully synthesized;The number average molecular weight of amphiphilic copolymers was around 42,000,and the PDI was 1.6.The specific rotation showed that the copolymer exhibited a large negative optical rotation.The drug-loading capacity showed that the micelles with the molar ratio o f the micelle core increased,and the drug carrying capacity gradually decreased;Micellar particles are spherical in aqueous solution,and the diameter of drug-loaded micelles is increased from 50 to 60nm to about 70 to 75 nm with respect to the blank micelles.The selective release results showed that in the two kinds of molar ratio of the micellar solution,the release rate of BOC-L-phenylalanine is faster and the release rate is higher than BOC-D-phenylalanine.The different release of enantiomers of micelles with molar ratios of 5:1 and 7.5:1 were 3%and 5%,respectively,indicating that the polymer has the ability to recognize BOC-D-phenylalanine.NMR demonstrated that the enantiomer proton signals moved to the low field and split,and the ratio of sp litting is the same as the ratio of the added enantiomers?L:D?3:2??.?2?A photosensitivity amphiphilic copolymer was synthesized using methacryloyloxyethylcinnamate?CEMA?,MALMA and MPEGAA as monomers,and micellar solution was prepared.The photosensitivity characteristics and the selective release effect of the micellar solution were examined.FT-IR,¹H NMR,GPC,TEM,polarimeter and UV spectrophotometer results show that:The CEMA monomers and amphiphilic copolymers were successfully synthesized.The number average molecular weight of amphiphilic copolymers was around 42,000,and the PDI was 1.6.The specific rotation showed that the copolymer exhibited a large negative optical rotation.The micellar particles undergoes[2ps+2ps]cycloaddition react ion under ultraviolet light,and after 25 minutes,the photocrosslinking ends;Micellar particles are spherical in aqueous solution,and the diameter of drug-loaded micelles is increased from 60 to 70 nm to about 100 nm with respect to the blank micelles.The selective release results showed that in the uncross-linked and cross-linked drug-loaded micelle solutions,the release rate of BOC-L-phenylalanine is faster and the release rate is higher than BOC-D-phenylalanine.The differences in uncrosslinked micelle release were 5.6%,4.2%,and 3.1%,while the differences in crosslinked micelle release were 6.3%,7.2%,and 6%.And the rate of release of the cross-linked sample relative to the uncross-linked sample decreases.NMR also confirmed that the polymer and BOC-D-phenylalanine can form more stable complexes.?3?The chiral polymer is bonded to the surface of silica gel with KH-590 and KH-570 silane coupling agent as the medium.KH-590 is bonded to the surface of silica gel to initiate the copolymerization of glycidyl methacrylate?GMA?,and then LMA is used to open the ring to prepare P?GMA-g-LMA?-SiO₂ particles?GM for short?.The other method is to bond KH-570 to the surface of silica gel to initiate the polymerization of MALMA monomer to prepare PMALMA-SiO₂ particles?M for short?.The polymerization kinetics of GMA on silica gel surface and the chiral recognition ability of two kinds of particles were investigated.The results of FT-IR,TG,SEM and UV spectra show that the synthesis of GM and M series particles is successful,and the polymer is bonded to the surface of silica gel in the form of chemical bonds.The grafting degrees of the chiral monomer LMN on GM1,GM2 and GM3 were 6.9 g/100 g,7.5 g/100 g and 9.1 g/100 g,respectively.The grafting degrees of the chiral monomers MALMA on M1,M2 and M3 were 7.8 g/100 g,12 g/100 g and 14.2 g/100 g,respectively.The two systems have a more stable complex with d-phenylalanine,the M and GM series of the same graft volume,and the M series are more adsorption than the GM series.