Construction Of Alanine Pillar[5] Modified Porous Channel Membrane And Transpotaion/Separation Of Chiral Drug

Chirality is the basic characteristic of life system.It is well known that the amino acids,sugars and phospholipids of life are highly uniform chiral features.The proteins and DNA are built by these small molecules by means of assembly are also chiral.However,chiral molecules have different biological activity in human body.When the structure of drug molecular contains chiral centers,the pharmacological and toxicological properties of the enantiomers often show significant differences.For example,the R-isomers of thalidomide has the calming effect,while S-isomers has the strong teratogenic effects.Therefore,after the incident of thalidomide,the national drug administration management regulations that it must separate stereo isomer of chiral drugs.And the researchers need to study the pharmacology,toxicology,metabolism in the development of new drugs.Otherwise it is not possible to obtain new drug approval.Therefore,the development of efficient chiral separation method is not only of theoretical significance,but also has practical value in the fields of chiral catalysis and pharmaceutical industry.The high specificity and selectivity of molecular recognition on the cell membrane channel of life inspired scientists to imitate the biological channel to construct the functionalized artificial channel membrane,which has attracted wide attention.Compared with the biological channel,the bionic artificial channel membrane provides a new method for people to design and develop various bionic nanochannels because of its stable and modified easily.Therefore,it is a meaningful but challenging task to construct the bionic membrane nanochannel for separate chiral drugs.The core problem is how to design the chiral functional nanochannel for the rapid selective transport of chiral drugs and achieve separation.Based on the above analysis,this paper mainly divided into three parts to carries out scientific questions as follows:1.According to the artificial conical porous nanochannel have the function on the identification of signal amplification because of rectification effect.Especially,the tip end reveals the stronger effect for the selective ability of chiral molecular.By building the L-alanine pillar[5]arene(LAP[5])modified tip end of biomimetic nanochannel,we study the selective transportation of cardiovascular drugs propranolol enantiomers in the bionic artificial membrane separation.The transmissibility of R-propranolol is much higher than that of S-propranolol in the nanochannel membrane.And the transmembrane transport selectivity coefficient αR/S=4.96.Furthermore,comparing with the transportion of bare nanochannel(αR/S=0.91)and the all-modified nanochannel(αR/S=3.96),we found that the L-alanine pillar[5]arene(LAP[5])modified tip end of nanochannel has better selevtive transport effect of chiral propranolol enantiomers.It can provide a new strategy for the development of the separation of chiral drugs.2.In life,the entire protein channel on the cell membrane has not only the asymmetric shape,but also the asymmetric cavity with the recognition sites.Based on the work in the previous chapter,we design L-and D-alanine pillar[5]arene modified into conical porous nanochannel to construct a chiral hybridization of two-element modified nanochannel in PET membrane.We want to increase the transmission rate of a single propranolol to achieve the goal of propranolol separation.Through the experiments of SEM,I/V curve and fluorescence confocal,it proved the successful construction of chiral hybridization of two-element modified nanochannel.Finally,under the condition of applied voltage,we did the transmission and separation experiments of the chiral propranolol.And we calculated the transmission rate of propranolol in the chiral hybridization of two-element modified nanochannel membrane.The membrane selective transmission coefficient αR/S=7.36.High performance liquid chromatography was used to detect chiral proportion of propranolol racemic form after separation by transport the membrane.3.Biofilms with liquid characteristics are sensitive to various stimuli including light,pressure,pH,temperature,humidity,electric field,magnetic field and so on.When the external stimulation is applied to the porous liquid membrane,the liquid membrane channel will open or close for the response behavior.For example,when a nanochannel membrane system is open,it allows ion transport or substance flow.Here,the liquid acts as a dynamic "gate valve" to realize controllable transport and separation of substance.In the macroscopic scale,the liquid has strong fluidity,so it is difficult to form a stable structure,which means it needs the porous solid membrane as support material.On the basis of the work in the previous chapter,we can increase the contact probability of chiral drugs with receptor molecules in a certain chiral selective separation ability to increase the circulation of chiral drugs at the same time.We use artificial micron solid membrane as a liquid membrane supporting to separate chiral propranolol enantiomers.Therefore,it can not only maintain the fluidity and permeability of liquid film,but also achieve the goal of chiral separation.