Xian-Hua Wang

Low cross-linked molecularly imprinted monolithic column prepared in molecular crowding conditions

Molecular crowding is a new approach to promoting molecular imprinting more efficiently. In this work, this concept was applied to the preparation of low cross-linked imprinted polymers in the presence of an immobilised template for stabilizing binding sites and improving molecular recognition. An imprinted monolithic column was synthesized using a mixture of 2,4-diamino-6-methyl-1,3,5-triazine (template), 2,4-diamino-6-(methacryloyloxy) ethyl-1,3,5-triazine (polymerisable template), methacrylic acid, ethylene glycol dimethacrylate, and polystyrene (molecular crowding agent). Some polymerization factors, such as template-monomer molar ratio, the composition of the porogen and crosslinking density, on the imprinting effect of resulting MIP monolith were systematically investigated. The results indicated that the imprinted monolithic columns prepared in the presence of molecular crowding agent retained affinity and specificity for template even when prepared with a level of cross-linker as low as 9%. Moreover, a stoichiometric displacement model for retention was successfully applied to evaluate the interaction between the solute and the stationary phase. Compared with the low cross-linked MIP prepared by conventional polymerization, the molecular crowding-based low cross-linked monolithic MIPs showed higher selectivity. The results suggested that molecular crowding is a powerful strategy to increase the effect of molecular imprinting at a low level of crosslinker.

Macromolecular crowding of molecular imprinting: A facile pathway to produce drug delivery devices for zero-order sustained release.

This paper reported the facile fabrication of drug delivery devices for zero-order sustained release by molecular crowding strategy of molecularly imprinting technology. Crowding-assisted molecularly imprinting polymers (MIPs) matrices were prepared by free-radical precipitation polymerization using aminoglutethimide (AG) as a model drug. The crowding effect was achieved by adding polystyrene as a macromolecular co-solute in pre-polymerization mixture. The MIP prepared under the non-MMC condition and the two corresponding non-imprinted particles were tested as controlled vehicles. The release profiles presented zero-order behaviors from two crowding-assisted polymers, the duration of approximately 18h for the crowding-assisted MIP and 10h for the crowding-assisted NIP, respectively while AG were all very rapid released from the other two controlled particles (85% occurring in the first hour). The BET surface area and pore volume of the crowding-assisted MIP were about ten times than those of the controlled MIP. The value of imprinting factor is 6.02 for the crowding-assisted MIP and 1.19 for the controlled MIP evaluated by the equilibrium adsorption experiment. Furthermore, the values of effective diffusivity (Deff) obtained from crowding-assisted MIP (10(-17)cm(2)/s) was about two orders of magnitude smaller than those from the controlled MIP, although the values of free drug diffusivity (D) were all found in the order of 10(-13)cm(2)/s. Compared with the commercial AG tablet, the MMC-assisted MIP gave a markedly high relative bioavailability of 266.3%, whereas the MMC-assisted NIP gave only 57.7%. The results indicated that the MMC condition can modulate the polymer networks approaciate to zero-order release of the drug and maintain the molecular memory pockets, even if under the poor polymerization conditions of MIPs preparation.

Synthesis of monodisperse molecularly imprinted microspheres with multi-recognition ability via precipitation polymerization for the selective extraction of cyromazine, melamine, triamterene and trimethoprim.

Through precipitation polymerization, three monodisperse molecularly imprinted polymers (MIPs) containing imprints of 2,4-diamino-6-methyl-1,3,5-triazine (DM), cyromazine (CY) or trimethoprim (TM), were synthesized using methacrylic acid as functional monomer, divinylbenzene as cross-linker, and a mixture of acetonitrile-toluene (90/10, v/v) as porogen. The morphology and selectivity of the MIPs were characterized and compared systematically. The MIPs had the best specific binding in pure acetonitrile, and the data of adsorption experiment were fitted well with Langmuir and Freundlich model. In addition, DM-MIPs showed the excellent binding and multi-recognition capability for CY, melamine (ME), triamterene (TA) and TM, and the binding capacity were 7.18, 7.56, 5.66 and 5.45μmol/g, respectively. Due to the pseudo template and the ability of multi-recognition, DM-MIPs as sorbent material could avoid the effect of template leakage on quantitative analysis. Therefore, DM-MIPs were used as a solid-phase extraction material to enrich ME, CY, TA and TM from different bio-matrix samples for high performance liquid chromatography analysis. Under the optimized conditions, the recoveries of three spiked levels in different bio-matrix samples were ranged from 80.9% to 91.5% with RSD≤4.2 (n=3).

Poly(glycidyl methacrylate) nanoparticle-coated capillary with oriented antibody immobilization for immunoaffinity in-tube solid phase microextraction: Preparation and characterization

A combination between modification with nanoparticles (NP) and oriented antibody immobilization (OAI) on the inner face of capillary was for the first time developed for immunoaffinity in-tube solid-phase microextraction (SPME) to promise high antigen extraction capacity. β2-microglobin (β2MG) and cystatin C (Cys-C) were selected as model antigens. Poly(glycidyl methacrylate) (PGMA) NPs were chemically immobilized onto the capillary by a ring-opening reaction. Antibodies for β2MG and Cys-C were immobilized on the NPs through OAI. Scanning electron micrograph of the OAI capillary clearly showed that the PGMA NPs were coated onto the inner surface of capillary in a dense monolayer. In addition, random antibody immobilized (RAI) capillaries and OAI capillaries without NP were also prepared as controls. The extraction capacities of OAI capillaries were 2.02 and 2.18mgm-1 for β2MG and Cys-C, and were about 5 and 6 times as many as RAI capillaries and OAI capillaries without NP, respectively. The resultant capillaries were used as in-tube SPME materials to enrich β2MG and Cys-C for particle-enhanced turbidimetric immunoassay. When using 1.0mgL-1 standard solutions, the recoveries of OAI capillaries, RAI capillaries and OAI capillaries without NP were 103.6% and 96.8%, 48.5% and 31.5%, and 24.2% and 25.7% for β2MG and Cys-C, respectively. Furthermore, the method quantitation limit by OAI capillaries was 5 and 10 times lower than that by RAI capillaries and OAI capillaries without NP, respectively. This result indicated that the NP-coated capillaries with OAI are more suitable for using as immunoaffinity in-tube SPME materials than that with RAI.

Enhancement of selective separation on molecularly imprinted monolith by molecular crowding agent

AbstractIn this study, a new molecularly imprinted polymer chiral stationary phase (MIP-CSP) was prepared utilizing molecular crowding agent for improvement the selective separation ability. S-amlodipine (S-AML), methacrylic acid (MAA), ethylene glycol dimethacrylate (EDMA), and polymethyl methacrylate (PMMA) were selected as template, functional monomer, cross-linker, and molecular crowding agent, respectively. The composition of formulas for MIP-CSP was optimized, and the permeability and structural feature of resultant MIP-CSP were characterized. The effect of mobile-phase composition, including ionic strength, pH, and organic modifier content, was investigated for achieving the selective separation of rac-amlodipine (rac-AML) on MIP-CSP. The baseline separation of rac-AML was achieved with resolution of 1.58, whereas no selective separation was observed on the imprinted monolith without molecular crowding agent. The perturbation chromatography method was successfully applied to evaluate the recognition mechanism of templates on MIP-CSP. The retention time of S-AML detected in typical analytical conditions was obviously greater than the time of negative peak derived from perturbation, which indicated the retention of template may be due to the imprinted cavities on MIP-CSP. Additionally, the result of Van’t Hoff analysis indicated that the chiral separation of rac-AML on MIP-CSP was an entropy-driven process, which supported the molecular imprinting theory. These results reveal that molecular crowding is a potential strategy for preparation of MIP-CSP with excellent selective separation ability. Graphical AbstractImprovement of chiral separation on molecularly imprinted monolith by molecular crowding condition

Synthesis of boronate-decorated polyethyleneimine-grafted porous layer open tubular capillaries for enrichment of polyphenols in fruit juices

A combination between modification with porous layer and grafting of polyethyleneimine (PEI) on the inner face of capillary was for the first time developed for boronate affinity in-tube solid-phase microextraction (SPME) material to enhance the extraction capacity for cis-diol-containing polyphenols. The successful synthesis of boronate-decorated polyethyleneimine-grafted porous layer open tubular (BPPLOT) capillary was confirmed by scanning electron micrograph, Fourier transform-infrared spectra and absorption experiments. The porous layer, PEI and boronate affinity provided high specific surface area, more binding sites for boronate groups and specific selectivity of BPPLOT capillary, respectively. The maximum binding quantity of BPPLOT capillary greatly improved, and ranged from 143 to 170 μg m-1 for cis-diol-containing polyphenols (catechin, chlorogenic acid, caffeic acid and epicatechin). A green method based on boronate affinity in-tube SPME was developed for separation and enrichment polyphenols, and some parameters of in-tube SPME were optimized. After in-tube SPME, HPLC with UV detection was used for quantitative determination of polyphenols. Recoveries of standard spiked cis-diol-containing polyphenols from fruit juice were between 80.9% and 102%, with intra-day and inter-day coefficient of variation ranging from 4.8% to 7.3% and 5.0% to 8.6%, respectively. Conversely, recovery of non-cis-diol-containing ferulic acid was no greater than 3.0%. These results suggested that the BPPLOT capillary could effectively separate and enrich cis-diol-containing polyphenols from real samples.