Zhao-Sheng Liu

Recent developments of molecularly imprinted polymer in CEC.

This review focuses on developments in the field of molecularly imprinted polymer (MIP) for CEC since August 2006. New technique of CEC‐based MIP, e.g. covalent approach through the formation of Schiff base, miniemulsion polymerization, non‐hydrolytic sol–gel methodology, MIP‐derivatized silica monolithic column, are discussed from the view of MIP preparation. Some thoughts on potential future directions are also expressed in this review.

Recent developments and applications of molecularly imprinted monolithic column for HPLC and CEC

As a new generation of stationary phases, monolithic supports have attracted significant interest in high-performance liquid chromatography (HPLC) and capillary electrochromatography (CEC) because of their ease of preparation, high reproducibility, versatile surface chemistry and rapid mass transport. Molecularly imprinted polymers (MIPs) are synthetic materials with high specific recognition ability to template molecule. The combination of monolithic column and MIPs integrates the high efficiency of modern chromatography and the high selectivity provided by MIPs. This review focuses on the recent developments and applications of all kinds of monolithic matrix, i.e. organic polymer-based and silica-based MIP monolith in HPLC and CEC mode.

CEC separation of ofloxacin enantiomers using imprinted microparticles prepared in molecular crowding conditions

Molecular crowding is a new concept to obtain molecularly imprinted polymers (MIPs) with greater capacity and selectivity, which could shift the equilibrium of a print molecule reacting with functional monomers in the direction of complex formation side. In this work, molecular crowding agent was first applied to the preparation of MIPs microparticles by precipitation polymerization. A new system of molecular crowding surrounding was developed, composed of polystyrene and tetrahydrofuran, in the presence of the template (S)‐ofloxacin. Partial filling capillary electrochromatography (CEC) was utilized to evaluate imprinting effect of the resulting microparticles by chiral separations of ofloxacin. Some important parameters in the preparation, i.e. template to monomer ratio, influence of cross‐linking monomers and functional monomer composition on the CEC separation of MIP microparticles were investigated. Baseline separation of ofloxacin (Rs=1.53) was obtained under optimized conditions and the highest theory plate of the later eluent (S)‐ofloxacin was 5400. The textural and morphological parameters for imprinted particles, such as Brunauer–Emmett–Teller surface areas, pore volumes and pore size distributions have also been determined. Compared to the MIP microparticle prepared by conventional precipitation polymerization, the (S)‐ofloxacin‐imprinted particles formed under molecular crowding conditions showed higher selectivity (α=1.09) and separation efficiency (<25 min) in the CEC mode.

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.

Coatings of one monomer molecularly imprinted polymers for open tubular capillary electrochromatography

One monomer molecularly imprinted polymer coatings were first synthesized in fused silica capillary columns with 2-methacrylamidopropyl methacrylate (MAM) as single functional monomer in addition to a cross-linking monomer. Since MAM may generate no or little EOF, a strategy of precursor of polymerization, which does not interfere with the formation of defined imprints, was used to introduce an ionizable functional monomer to generate a stable electroosmotic flow for electrochromatography (CEC) by post-polymerization hydrolization. The resulting MAM-based open-tubular imprinted capillary was able to separate enantiomers by means of CEC. The resolution of enantiomers separation achieved on S-amlodipine-imprinted capillary was up to 16.1. The strong recognition ability (selectivity factor was 3.23) and high column performance (theory plates was 26,053 plates m(-1)) of template were obtained. The MIP coatings were also prepared using either S-naproxen or S-ketoprofen as template molecule. The resolutions of enantiomers separation were 2.20 and 4.56, respectively. The results illustrate that the synthesis of MIP using one monomer is not only an experimental-simplified process, but also an approach to producing chiral stationary phase with high efficiency and selectivity.

Synthesis and theoretical study of molecularly imprinted monoliths for HPLC

Molecularly imprinted monoliths integrate the high permeability of monolithic materials and the high selectivity and affinity of molecularly imprinted polymers (MIP). Thus, in recent years, development of this novel MIP format in HPLC has expanded quickly, particularly use of organic materials. This review focuses on the principal aspects of good practice in polymerization, theoretical studies, and recent developments in molecularly imprinted monoliths. Some thoughts on perspectives of MIP monoliths are also expressed.

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.

Preparation and characterization of imprinted monolith with metal ion as pivot

This report provided the first example of using pivot concept to prepare monolithic molecularly imprinted polymers (MIPs) with ketoprofen (KET) imprints, in which metal ions were employed as mediator between the functional monomer and the template to achieve higher fidelity of imprint. To solve metal ions in pre-polymerization system, a new ternary porogen of dimethyl sulfoxide-toluene-isooctane was developed for preparation of MIP monoliths with high porosity and good permeability. The effect of polymerization parameters such as the nature of metal ions, the ratio of template to metal ion and the degree of crosslinking, on the permeability, morphology and affinity of the metal ion mediated MIP monolith were studied. The experiments demonstrated that Ni(2+), Co(2+) and Zn(2+) can be applied as pivot to prepare KET-imprinted monolith. Relative to monolithic MIP without metal ions, all the ion-mediated macropore MIP monoliths showed enhanced permeability, capacity factor and selectivity factor. High permeability (1.06×10(-7)mm(2)) was obtained on the Co(2+)-mediated MIP monolith and great selectivity factor (3.84) was achieved on the Ni(2+)-mediated one. The stoichiometric displacement model was constructed to investigate the recognition mechanism of metal-ion mediated MIP. The results indicate that metal ion as pivot not only improves the affinity but also allows the fine-tuning on the macroporous structure of MIP monolith.

Preparation and characterization of enrofloxacin-imprinted monolith prepared with crowding agents

Molecular crowding is a new approach to promoting molecular imprinting more efficiently. In this work, this concept was applied to the preparation of imprinted monoliths in the presence of molecular crowding agent for stabilizing binding sites and improving molecular recognition. The imprinted monolithic column was synthesized using a mixture of enrofloxacin (template), methacrylic acid, ethylene glycol dimethacrylate, and polystyrene (molecular crowding agent). Some polymerization factors, such as template-monomer molar ratio and the composition of the porogen, on the imprinting effect of resulting MIP monolith were systematically investigated. Moreover, a stoichiometric displacement model for retention was successfully applied to evaluate the interaction between the solute and the stationary phase. Compared with the MIP prepared by conventional polymerization, the molecular crowding-based monolithic MIPs showed higher selectivity. The results suggested that molecular crowding is a powerful strategy to increase the effect of molecular imprinting.

Chiral separation of racemic mandelic acids by use of an ionic liquid-mediated imprinted monolith with a metal ion as self-assembly pivot

AbstractA new chiral stationary phase based on molecularly imprinted polymers (MIP) was prepared in ionic liquid by use of the metal pivot concept. Imprinted monoliths were synthesized by use of a mixture of R-mandelic acid (template), 4-vinylpyridine, ethylene glycol dimethacrylate, and several metal ions as pivot between the template and functional monomer. A ternary mixture of dimethyl sulfoxide–dimethylformamide–[BMIM]BF4 containing metal ions was used as the porogenic system. Separation of the enantiomers of rac-mandelic acid was successfully achieved on the MIP thus obtained, with resolution of 1.87, whereas no enantiomer separation was observed on the imprinted monolithic column in the absence of metal ions. The effects of polymerization conditions, including the nature of the metal ion and the ratios of template to metal ions and template to functional monomer, on the chiral separation of mandelic acid were investigated. The results reveal that use of metal ions as a pivot, in combination with ionic liquid, is an effective method for preparation of a highly efficient MIP stationary phase for chiral separation. FigureA new chiral stationary phase based on molecularly imprinted polymers (MIP) was prepared in ionic liquid by use of the metal pivot concept