Preparation And Selective Adsorption Properties Of R-bupivacaine Imprinted Polymer Based On Tartrate-based Chiral Functional Monomer

Optically pure tartaric acid is an important chiral resolving agent,which can be employed for the diastereomeric crystallization resolution of various alkaloid racemates.Also,tartaric acid derivatives are widely used in chiral extraction and Chiral chromatographic separation of drug enantiomers.Enantiomer adsorption separation based on chiral molecularly imprinted polymers(MIPs)is a potential and promising method for enantiomeric resolution.Existing MIPs apply achiral compounds as functional monomers,which have low chiral recognition and selective adsorption performance,and are difficult to be used as enantiomer adsorption resolution media.In this paper,three chiral functional monomers based on tartaric acid were synthesized.The molecularly imprinted polymer of R-bupivacaine was prepared by bulk polymerization using photo-initiated polymerization.The structure,and thermal stability of the as-prepared MIPs and its selective adsorption of R-bupivacaine were evaluated.The main research contents are as follows:(1)Preparation of chiral functional monomers based on tartaric acid.Diacryloyl tartaric acid was synthesized by acylation of hydroxyl groups on tartaric acid using acryloyl chloride.Diallyl tartaric acid monomer was synthesized by the reaction of tartaric acid with allyl chloride.Diallyloxybenzoyltartaric acid was prepared via the synthesis of allyloxybenzoic acid using bromopropene and p-hydroxybenzoic acid,and followed esterification with tartaric acid.The purity of related intermediate and functional monomers were analyzed by HPLC,and the product structure was analyzed and confirmed by IR and NMR.(2)Preparation of chiral molecularly imprinted polymer to resolve bupivacaine racemate.R-bupivacaine template molecules were tried to imprint and polymerize with three chiral functional monomers through photoinitiation respectively.Under the trigger of AIBN,diacryloyl tartaric acid can be cross-linked with EGDMA,and the MIPs and NIPs were characterized and analyzed by SEM,IR,TGA and BET.Taking the enantiomeric excess value(e.e.value)of R-bupivacaine as the objective function,the effects of solvent type,bupivacaine concentration,liquid-solid ratio and adsorption temperature on the selective adsorption of R-bupivacaine by MIPs and NIPs were discussed.Under optimized selective adsorption conditions,the e.e.values of R-bupivacaine adsorbed on MIPs and NIPs were 53.8% and 26.0% respectively.In addition,the mechanism of chiral adsorption separation of racemic Bupivacaine by MIPs was preliminarily discussed.The Adsorption thermodynamics and kinetics of MIPs and NIPs.The equilibrium adsorption amount and isotherm adsorption line of R-bupivacaine or S-bupivacaine on MIPs and NIPs were measured at 303 K,313K and 323 K respectively.The results show that: lower temperature is more conducive to improving the selective adsorption capacity of MIPs or NIPs.The correlation between the isotherm data of R-Bupivacaine on MIPs or NIPs and the Freundlich model is better than the Langmuir model.Based on the graph drawn by the Scatchard equation,it is inferred that there are two different types of binding sites for MIPs.The calculated thermodynamic parameters indicate that the adsorption of MIP to R-bupivacaine is spontaneous and exothermic.At a temperature of 303 K,the adsorption process of R-bupivacaine by MIP or NIP basically reached equilibrium in about 30 minutes.The fitting results of the adsorption process show that the quasi-second-order kinetic equation can better express the kinetic adsorption process of R-bupivacaine by MIP or NIP.