Dissertation Fabrication Of Functional Nanochannels And Micropores For Chiral Transport And Resolution Of Drugs

In recent years,the demand for chiral drugs has increased rapidly.Drug enantiomers have great differences in pharmacology and toxicity.Therefore the development of efficient chiral resolution method becomes an urgent scientific task.Membrane resolution has the advantages of large resolution amount,less time consuming,continuous operation,and environmental friendliness,which is considered as one of the most potential chiral resolution methods.Chiral nanochannel,which can selectively transport drug enantiomers,has been a research hotspot in the field of chiral resolution membrane.However,the selectivity of chiral resolution remains the most critical scientific issue for chiral nanochannel.There are two key points related to enantioselectivity:one is the diameter of the nanochannel,improving the size matching between the channel and the drug molecule is one strategy to improve the enantioselectivity;the other is the chiral receptor,amplifying its affinity difference between drug enantiomers is another strategy.To solve the scientific issue of selectivity in drug enantiomer resolution based on chiral nanochannels,while maintaining flux,this dissertation contains five parts from two directions of size matching and asymmetric modified receptors as following:1.To improve the size matching between nanochannel and drug enantiomers,we in-situ synthesize the covalent organic framework(COF)in nanochannels.L-tyrosine functionalized covalent organic framework(L-Tyr-COF)packed nanochannel is fabricated for chiral resolution of naproxen.Compared with monolayer modified chiral nanochannels,the covalent organic framework realizes the size matching between nanochannel and drug enantiomers,porosity,and modification density,thus the chiral COF packed nanochannel possesses highe enantioselectivity and high flux for chiral resolution.2.In practical application,most resolution membranes are microporous membranes to ensure the flux,where is a dilemma between enantioselectivity and flux.We in-situ synthesize L-Try-COF in micropores with different diameters with the same method.Compared with monolayer modified micropores,the enantioselectivity and flux of the L-Tyr-COF packed micropores increase with micropore diameter,of which the reason is increased L-Tyr modification density and porosity.The padding of chira COF in micropores solves the dilemma between enantioselectivity and flux and realizes the resolution of naproxen with high enantioselectivity and high flux.3.Except for huge channels,the unidirectional transport regulated by the single chiral receptor also prevent a high enantioselectivity.The life system provides another efficient separation modelantiport.Based on the synergistic effect of multiple receptors,the sodium-potassium pump accurately drives reverse transmembrane transport of Na+ and K+.We propose to construct a bionic chiral antiporter for drug resolution.D-Tyr is added as a chiral receptor for co-recognition with L-Tyr.A twostep asymmetric modification method is used to establish the tyrosine enantiomers asymmetric modified dumbbell-shaped nanochannels.The asymmetric modified nanochannel simultaneously responds to naproxen enantiomers,and the selectivity ratio is 100 times higher than that of the single receptor modified nanochannels.The region-selective binding of drug enantiomers to chiral receptors induces inverse electrostatic potential gradients in the nanochannel,driving the antiport and chiral resolution of naproxen.4.Electrostatic potential-driven antiport is suitable for the drugs easy to ionize,but not for neutral drugs(such as propranolol).In order to realize the antiport and chiral resolution of propranolol,we designe a wetting-adjustable asymmetric modified nanochannel for wetting gradient-driven fluid selfmotion.The hydrophobic phenylalanine dipeptide enantiomers are used as receptors to recognize hydrophilic drug propranolol enantiomers.The region-selective binding between drug enantiomers and receptors induces reverse wetting gradients in asymmetric nanochannel,as the driving force of the antiport and chiral resolution of neutral drug propranolol.5.After analysis of the effect of chiral COF padding and multi-receptor asymmetric modification to enantioselectivity and flux of chiral resolution,we propose to combine these two strategies to fabricate the asymmetric modified COF packed micropores for chiral resolution of naproxen,propranolol,and ibuprofen.The optical purity of separation chiral drugs reached 95%,while the flux reached 10-3 molm-2h-1.Additionally,the asymmetric modified COF packed microporous possesses good solvent resistance and long service life.It is a chiral resolution membrane with high enantioselectivity,high flux,and universality.