Preparation Of Surface Imprinted Material Of Chiral Drug Mandelic Acid And Study On Its Recognition And Chiral Enantioseparation Property

At present,chiral drugs has a large proportion of the drugs currently produced,the single enantiomers of drugs will show different pharmacological effects in human body,and even have some side effects.Therefore,it has become an important development goal of medical science to try to obtain optically pure chiral drugs.In this study,surface imprinted materials MIP-PMAA/SiO₂ and MIP-PDMAEMA/Si O₂ of S-mandelic acid were prepared by using the novel surface-imprinting technique of “ synchronously graft-polymerization and crosslinking”,in non-aqueous media and aqueous media,in which S-mandelic acid was used as the template molecule.The prepared imprinted materials MIP-PMAA/SiO₂ and MIP-PDMAEMA/SiO₂ had good selective recognition performance and chiral resolution ability for racemic mandelic acid,the study has practical value for the extraction and separation of mandelic acid.First,MPMS/SiO₂ modified particles were prepared by modifying the surface of SiO₂ particles in non-aqueous,in which ?-mercaptopropyl trimethoxysilane?MPMS?was used as the coupling agent.The initiator system composed by the benzoyl peroxide?BPO?and thiol group was used to induce the polymerization of monomer methacrylic acid?MAA?on the surface of the particles,and the grafted particles PMAA/SiO₂ were successfully prepared.The two types particles PMAA/SiO₂ and MPMS-SiO₂ were characterized with FTIR,SEM and TGA,the effect of reaction conditions on the grafting reaction of MAA was studied;The results showed that the optimum conditions for preparation of graft particles PMAA/SiO₂: the system temperature is 70?,the proportion of monomers in the reaction system was 13%,the used amount of initiator was 1.0% of MAA,the grafting degree of PMAA could get up to20.21g/100 g at this conditions.Next,the interaction between the graft particles PMAA/SiO₂ and mandelic acid was investigated,in which the graft particles PMAA/SiO₂ was preparated at optimum conditions.The experimental results showd that the mandelic acid molecule and the carboxyl of macromolecular chain of PMAA can come into being hydrogen bonding interaction with mandelic acid molecules and PMAA/SiO₂ had faible binding force effect on mandelic acid molecule under the interaction,the adsorption capacity can reach 146 mg/g in DMF at 25?;.With the increase of temperature,the adsorption capacity of grafted particles to mandelic acid decreased.Modified particles AMPS/SiO₂ were prepared by modifying the surface of SiO₂ particles in non-aqueous,in which ?-aminopropyl trimethoxysilane?AMPS?was used as the coupling agent;The initiator system composed by the?NH4?2S2O8 and amino group was used to induce the graft-polymerization of monomer dimethylaminoethyl methacrylate?DMAEMA?on the surface of AMPS/Si O₂ particles,PDMAEMA/SiO₂ was obtained;the AMPS/SiO₂ and PDMAEMA/SiO₂ particles were characterized by the same method as described above;the effect of reaction conditions on the grafting reaction of DMAEMA was studied The results showed that the optimum conditions for the preparation of graft particles PDMAEMA/SiO₂:the system temperature is 35?,the proportion of monomers in the reaction system was 14%,the used amount of initiator was 1.0% of DMAEMA,the degree of graft could reach24.8g/100 g at this conditions.Next,the interaction between the graft particles PDMAEMA/SiO₂ and mandelic acid was investigated.The experimental results showd that the mandelic acid molecule and tertiary amino of the macromolecular chain PDMAEMA could come into being hydrogen bonding interaction and lectrostatic interaction,and PDMAEMA/SiO₂ particles had faible adsorption capacity effect on mandelic acid by right of the hydrogen bonds and electrostatic interaction.At 25?,pH=3,the adsorption capacity was get up to 200mg/g in aqueous medium;With the increase of temperature,the adsorption capacity of grafted particles to mandelic acid decreased.In non-aqueous media,based on the hydrogen bonding interaction between graft polymer PMAA and mandelic acid molecules,MAA was used as monomer,EGDMA was used as linking agent,MIP-PMAA/Si O₂ were prepared under this circumstance;static adsorption methods,dynamic adsorption methods and competitive adsorption experiments were adopted to study the recognition selectivity and chiral resolution performance for chiral mandelic acid.The results showd that the static adsorption capacity was 146 mg/g,and the dynamic adsorption capacity was about 140 mg/g;Relative to non-template molecule R-mandelic acid,the selectivity coefficient of MIP-PMAA/SiO₂ for template molecule was 4.9;After chiral resolution experiment,the enantiomeric excess of R-mandelic acid was 40% in the supernatant,and the enantiomeric excess of S-mandelic acid was 81% in the eluent.Furthermore,the most suitable imprinting conditions: the proportion of crosslinking agent EGDMA and monomer MAA was 1:3,the proportion of template molecule S-mandelic acid and monomer MAA was 1:3.Finally,In aqueous media,based on the hydrogen bonding interaction and electrostatic interaction between graft polymer PDMAEMA and mandelic acid molecules,the S-mandelic acid molecule surface imprinted materials MIP-PDMAEMA/SiO₂ was performed successfully with DMAEMA as functional monomer and 2,2'-dichlorodiethylether?DCEE?as crosslinking agent in a aqueous medium,and then were prepared successfully;static adsorption methods,dynamic adsorption methods and competitive adsorption experiments were adopted to study the recognition selectivity and chiral resolution performance for chiral mandelic acid.The results showd that the static adsorption capacity was 205 mg/g,and the dynamic adsorption capacity was about 208.98 mg/g;Relative to non-template molecule R-mandelic acid,the selectivity coefficient of MIP-PDMAEMA/SiO₂ for template molecule was 4.3;After chiral resolution experiment,the enantiomeric excess of R-mandelic acid was 30% in the supernatant,and the enantiomeric excess of S-mandelic acid was 76% in the eluent.Furthermore,the most suitable imprinting conditions: the proportion of crosslinking agentDCEE and monomer DMAEMA was 1:3,the proportion of template molecule S-mandelic acid and monomer DMAEMA was 1:4.