Preparation And Properties Of S-Amlodipine Magnetic Surface Imprinted Material

As a chiral drug,amlodipine has two different enantiomeric structures,S-amlodipine and R-amlodipine,and their biological activity and pharmacological effects are different.In terms of efficacy,S-amlodipine is a thousand times stronger than R-amlodipine.In terms of harm to the human body,S-amlodipine has less side effects than R-amlodipine,and will not cause damage such as edema and heart palpitations.Therefore,the chiral resolution of amlodipine is very important.This topic combines inorganic magnetic materials and surface molecular imprinting technology,and adopts a new surface molecular imprinting technology of"synchronization of graft polymerization and crosslinking imprinting"to prepare S-amlodipine magnetic surface molecularly imprinting material MMIP-Fe₃O₄@SiO₂-PAM,while studying the chiral recognition and resolution performance of magnetic surface imprinting materials for amlodipine,which provides a theoretical reference for the study of chiral resolution of amlodipine.First,by solvothermal method,using ethylene glycol as the reaction medium,Fe³⁺in ferric chloride hexahydrate is used for nucleation and growth of magnetic nanomaterials under high temperature and high pressure conditions to prepare magnetic nanoparticles Fe₃O_4.Then,the tetraehyl orthosilicate is hydrolyzed in alkaline alcohol-water mixed solution to generate silica,which is coated on the surface of Fe₃O₄magnetic nanoparticles,and the surface of Fe₃O₄magnetic nanoparticles is modified to obtain magnetic nanoparticles Fe₃O₄@SiO₂.Then in a non-aqueous medium,3-aminopropyltriethoxysilane containing amino group was used as coupling agent to modify the surface of Fe₃O₄@SiO₂magnetic nanoparticles to prepare magnetic nanoparticles Fe₃O₄@SiO₂-NH₂.Then,in the ethanol solvent,the amino groups on the surface of Fe₃O₄@SiO₂-NH₂and ammonium persulfate form an initiation system to cause the functional monomer acrylamide（AM）to undergo graft polymerization,and then graft to the magnetic nanoparticles Fe₃O₄@SiO₂-NH₂surface,and the magnetic grafted particles Fe₃O₄@SiO₂-PAM were prepared.The magnetic grafted particles Fe₃O₄@SiO₂-PAM were characterized by infrared spectroscopy,scanning electron microscopy,vibration sample magnetometer and thermal weight loss analysis method,and the preparation conditions of the magnetic grafted particles Fe₃O₄@SiO₂-PAM were investigated.The results showed that the magnetic grafted particles with the maximum grafting degree of 176.8 mg/g were obtained by adding 0.4 g magnetic nanoparticles Fe₃O₄@SiO₂-NH₂in 50m L ethanol solvent,10 m L acrylamide monomer with mass fraction of 12%,0.1 g initiator ammonium persulfate and grafting polymerization at40℃for 8h.The prepared magnetic grafted particles Fe₃O₄@SiO₂-PAM have good magnetic properties and magnetic responsiveness,and the saturation magnetic intensity is 52.42 emu/g.Then,the adsorption performance of magnetic grafted particles Fe₃O₄@SiO₂-PAM for amlodipine was studied.The results show that the electrostatic force and hydrogen bonding force are formed between the magnetic grafted particles and amlodipine,which makes the magnetic grafted particles Fe₃O₄@SiO₂-PAM have a strong adsorption effect on amlodipine.When the adsorption temperature is 30℃,the p H of the solution is 7,and the adsorption time is 3.5h,the maximum adsorption capacity of magnetic grafted particles Fe₃O₄@SiO₂-PAM reaches 241 mg/g.Finally,in a non-aqueous medium,a new molecular imprinting technology of"synchronization of graft polymerization and cross-linking imprinting process"is adopted,with magnetic nanoparticles Fe₃O₄@SiO₂-NH₂as the carrier,and S-amlodipine as the imprinting molecule.Under the action of ethylene glycol diglycidyl ether（EGDE）,the magnetic surface molecularly imprinted material MMIP-Fe₃O₄@SiO₂-PAM was successfully prepared.The chiral recognition and resolution performance of magnetic imprinted material MMIP-Fe₃O₄@SiO₂-PAM for the template molecule S-amlodipine were investigated by static adsorption,dynamic adsorption and competitive adsorption methods.The results show that the magnetic surface molecularly imprinted material MMIP-Fe₃O₄@SiO₂-PAM has good performance of recognition,selection and chiral resolution of S-amlodipine.The dosage of template molecule S-amlodipine and the amount of cross-linking agent ethylene glycol diglycerol ether were the main factors affecting the selectivity of the magnetic surface molecular imprinting material MMIP-Fe₃O₄@SiO₂-PAM.The functional monomer acrylamide and the template molecule S-amlodipine under the condition that the material ratio of amlodipine is 4:1,and the material ratio of functional monomer acrylamide and crosslinking agent ethylene glycol diglycidyl ether is 5:3,the magnetic molecular imprinting material has the highest recognition and selection performance for S-amlodipine,with a selectivity coefficient of 4.56.The optical purity（ee%）of the separated S-amlodipine and R-amlodipine were 63.28% and 83.64%,respectively.