Won Jo Cheong

Molecular imprinted polymers for separation science: A review of reviews

Molecular imprinted polymer is an artificial receptor made by imprinting molecules of a template in a polymer matrix followed by removing the template molecules via thorough washing to give the permanent template grooves. They show favored affinity to the template molecule compared to other molecules, and this property is the basic driving force for such diverse application of this techniques. Such techniques have been increasingly employed in a wide scope of applications such as chromatography, sample pretreatment, purification, catalysts, sensors, and drug delivery, etc., mostly in bioanalytical areas. A major part of them is related to development of new stationary phases and their application in chromatography and sample pretreatment. Embodiments of molecular imprinted polymer materials have been carried out in a variety of forms such as irregularly ground particles, regular spherical particles, nanoparticles, monoliths in a stainless steel or capillary column, open tubular layers in capillaries, surface attached thin layers, membranes, and composites, etc. There have been numerous review articles on molecular imprinted polymer issues. In this special review, the reviews in recent ca. 10 years will be categorized into several subgroups according to specified topics in separation science, and each review in each subgroup will be introduced in the order of date with brief summaries and comments on new developments and different scopes of prospects. Brief summaries of each categories and conclusive future perspectives are also given.

Recent applications of molecular imprinted polymers for enantio-selective recognition.

Molecular imprinted polymer (MIP) techniques have been increasingly used in a variety of fields including chromatography, sample pretreatment, purification, sensors, drug delivery, and catalysts, etc. MIP is a specific artificial receptor that shows favored affinity to the template molecule. The cavities of the template are produced by carrying out polymerization of a reaction mixture followed by eliminating the template molecules by washing. Various forms of MIP materials have been prepared for diverse applications including irregularly ground particles, regular spherical particles, nanoparticles, monoliths in a stainless steel or capillary column, open tubular layers in capillaries, membranes, surface attached thin layers, and composites, etc. When an enantiomer is used as the template, then the resulting MIP can show capability of enantiomeric recognition between the pair of enantiomers. In this review, progresses in applications of enantio-selective recognition by MIPs will be critically reviewed for the recent period since 2007.

Preparation of an open-tubular capillary column with a monolithic layer of S-ketoprofen imprinted and 4-styrenesulfonic acid incorporated polymer and its enhanced chiral separation performance in capillary electrochromatography

Enhanced chiral separation performance has been observed for ketoprofen enantiomers in capillary electrochromatography (CEC) with an open-tubular (OT) column prepared with a specific molecule imprinted polymer (MIP) on the innerwall of 50mum ID capillary. The column was prepared by in situ thermal polymerization inside the pretreated and silanized fused silica capillary. A specific diluted monomer mixture composed of S-ketoprofen, methacrylic acid (MAA, functional monomer), ethylene glycol dimethacrylate (EDMA, cross-linker), and 4-styrenesulfonic acid (4-SSA) dissolved in 9/1 (v/v) acetonitrile/2-propanol was used to fabricate the OT-MIP layer. 4-SSA was added to form a MIP layer capable of stable and strong electro-osmotic flow (EOF) over the pH range of this study securing CEC elution of ketoprofen having partial negative charge near the optimized pH. Various parameters such as buffer pH, organic modifier composition, salt concentration, and applied potential have been optimized for CEC chiral separation of ketoprofen enantiomers. Very good separation selectivity and efficiency were observed, thus the chromatographic resolution of ketoprofen enantiomers was as high as 10.5, and the number of theoretical plates of R-ketoprofen, 156,000/m (40,000/m for S-ketoprofen), which proves that the OT-MIP-CEC type approach is a promising strategy in MIP study.

Simultaneous determination of water-soluble vitamins excreted in human urine after eating an overdose of vitamin pills by a HPLC method coupled with a solid phase extraction.

We have applied a quick and convenient method for determining water-soluble vitamins excreted in human urine. We found that the Sep-Pak C(18) cartridge was useful for preconcentration and recovery of water-soluble vitamins in urine with minimized loss of vitamins. The recovery of vitamins was well over 90%. The separation was carried out by gradient elution with 90/10 (v/v%) methanol/water with 0.1% trifluoroacetic acid (TFA) and water with 0.1% TFA on a muBondapak C(18) column. The separation was completed within 15 min. We measured concentrations of water-soluble vitamins excreted in urine after swallowing an overdose of vitamin pills on purpose, and found that the concentration of each vitamin increased rapidly to the maximum in 2-3 h and decreased swiftly.

Comprehensive overview of recent preparation and application trends of various open tubular capillary columns in separation science.

Open tubular (OT) capillary columns have been increasingly used in a variety of fields of separation science such as CEC, LC, and SPE. Especially their application in CEC has attracted a lot of attention for their outstanding separation performance. Various forms of OT stationary phase materials have been employed such as in-situ prepared polymers, molecular imprinted polymers (MIPs), brush ligands, host ligands, block copolymers, aptamers, carbon nanotubes, polysaccharides, proteins, tentacles, nanoparticles, monoliths, and polyelectrolyte multi-layers. They have been prepared either in the chemically bound format or physically adsorbed format. Sol-gel technologies and nanoparticles have been sometimes involved in their preparation. There have been also some unique miscellaneous studies, for example, adopting preferentially adsorbed mobile phase components as stationary phases. In this review, recent progresses since mostly 2007 will be critically discussed in detail with some summarized descriptions for the work before the date.

Preparation of open tubular molecule imprinted polymer capillary columns with various templates by a generalized procedure and their chiral and non-chiral separation performance in CEC

A generalized preparation procedure of open tubular (OT) molecule imprinted polymer (MIP) columns is proposed for a number of templates with acidic functionality such as profen drugs and others. The template (S‐enantiomer) was mixed with methacrylic acid, ethylene glycol dimethacrylate and 4‐styrenesulfonic acid, dissolved in a porogen mixture of ACN/2‐propanol (9/1), and incubated in a pretreated and silanized fused silica capillary by the thermal non‐covalent polymerization procedure. The whole preparation procedure was exactly the same for all the MIP capillaries except for the selection of template. Nevertheless, the morphologies of the MIP layers were markedly variant depending upon the choice of template. The separation efficiency of each OT‐MIP column for chiral separation of R‐ and S‐enantiomers was examined and tuned to obtain the best separation efficiency by changing the chromatographic parameters such as eluent composition and pH. Different optimized conditions were obtained for different OT‐MIP columns. Nevertheless, a unified eluent could be used to obtain still quite satisfactory results. Non‐chiral separation of the MIP columns were also examined in the unified eluent with two sets of test mixtures, that is, a mixture of alkylbenzenes and a mixture of small polar solutes. The chiral and non‐chiral separation of this study resulted in very good separation efficiencies. This work is the very first study for the generalization of preparation of OT‐MIP columns for a number of templates.

Long open tubular molecule imprinted polymer capillary columns with excellent separation efficiencies in chiral and non‐chiral separation by capillary electrochromatography

Long open tubular S‐ketoprofen molecule imprinted polymer capillary columns (1, 2, and 3 m) with the number of theoretical plates (N) over a million for both chrial and non‐chiral CEC separation have been prepared. Chiral separation of racemic ketoprofen and non‐chiral separation of other profen drugs have been achieved with excellent efficiency and good selectivity after optimization of the chromatographic conditions. The N value per column was not proportional to the effective column length although it was increased with the column length. This study has shown the outstanding prospect of the strategy to form a porous and rugged open tubular layer in a moderately long (1 m) capillary column in molecule imprinted polymer‐CEC studies.

Open tubular layer of S-ofloxacin imprinted polymer fabricated in silica capillary for chiral CEC separation.

An open tubular molecule imprinted polymer (OT-MIP) capillary column has been prepared for chiral separation of ofloxacin enantiomers in CEC. The S-ofloxacin imprinted OT column was fabricated by thermally initiated non-covalent polymerization procedure inside a pretreated and silanized fused silica capillary. The template molecule was incorporated with methacrylic acid (MAA), ethylene glycol dimethacrylate (EDMA) and 4-styrenesulfonic acid (4-SSA) and dissolved in a porogen mixture of ACN/2-propanol (9:1). The separation efficiency of the 4-SSA MIP column was found quite better than that of the MIP column without 4-SSA. It has been demonstrated that our OT-MIP column can separate ofloxacin enantiomers with excellent chiral separation efficiency after tuning the various chromatographic conditions. The optimized chromatographic eluent was 85:15, v/v%, ACN/60 mM sodium acetate at pH 7. The separation efficiency and selectivity of chiral separation of this study were far better than those obtained by previous methods for chiral separation of R- and S-ofloxacin.

Open tubular capillary columns with basic templates made by the generalized preparation protocol in capillary electrochromatography chiral separation and template structural effects on chiral separation capability

Some open tubular (OT) molecule imprinted polymer (MIP) silica capillary columns have been prepared using atenolol, sulpiride, methyl benzylamine (MBA) and (1-naphthyl)-ethylamine (NEA) as templates by the pre-established generalized preparation protocol. The four MIP thin layers of different templates showed quite different morphologies. The racemic selectivity of each MIP column for the template enantiomers was optimized by changing eluent composition and pH. The template structural effects on chiral separation performance have been examined. This work verifies the versatility of the generalized preparation protocol for OT-MIP silica capillary columns by extending its boundary toward templates with basic functional group moieties. This study is the very first report to demonstrate a generalized MIP preparation protocol that is valid for both acidic and basic templates. The chiral separation performances of atenolol and sulpiride by the MIPs of this study were found better than or comparable to those of atenolol and sulpiride obtained by non-MIP separation techniques and those of some basic template enantiomers obtained by MIP based techniques.

Thermodynamic properties for the solute transfer from the mobile to the stationary phase in reversed phase liquid chromatography obtained by squalane-impregnated C18 bonded phase

Abstract We have devised a reversed phase chromatographic system which secured a simple retention mechanism and showed reproducible solute retention over a long period of time. We used a squalane impregnated C 18 phase in a thermostated system with extreme care, and obtained retention data of some selected solutes (benzene, toluene, ethylbenzene, phenol, and acetophenone) at 25, 30, 35, 40, 45, and 50°C in aqueous methanol eluents. The van’t Hoff plots were nicely linear, thus we calculated dependable enthalpies and entropies of solute transfer from the mobile to the stationary phase based on three independent retention measurements on different days (or weeks). We observed that the solute transfer from the mobile to the stationary phase was enthalpically favorable and entropically unfavorable in general except for highly aqueous mobile phases. The enthalpic contribution to the overall solute transfer free energy was found generally more important than the entropic contribution. The cavity formation effect was found the major factor that governs the solute distribution between the mobile and stationary phases for methanol-rich mobile phases while the hydrophobic effect became significant in highly aqueous mobile phases. Comparison of our data with the literature data leaded to the conclusion that C 18 stationary phases with a high ligand density generally follow a partition mechanism while a C 18 phase with a low ligand density follows an adsorption-like mechanism.