Development and application of a thin-film molecularly imprinted polymer for the measurement of mycophenolic acid in human plasma.

BACKGROUND: Mycophenolic acid (MPA) is used to suppress the immune response following organ transplantation; however, complex pharmacokinetic behavior and a large interpersonal variability necessitate therapeutic drug monitoring. To overcome the limitations of current sample preparation techniques, we present a novel thin-film molecularly imprinted polymer (TF-MIP) extraction device as part of a simple, sensitive, and fast method for analysis of MPA from human plasma. METHODS: Mycophenolic acid is extracted from plasma using a tailor-made TF-MIP that is subsequently desorbed into an organic solvent system compatible with mass spectrometry. The MIP yielded higher recovery of MPA relative to a corresponding non-imprinted polymer. The method allows for the determination of MPA in 45 min including analysis time and can be scaled for high throughput to process as many as 96 samples per hour. RESULTS: The method gave an LOD of 0.3 ng mL-1 and was linear from 5 to 250 ng mL-1 . Patient plasma samples (35 µL) were diluted using charcoal-stripped pooled plasma to a final extraction volume of 700 µL; when MPA in patient plasma is high, this ratio can easily be adjusted to ensure samples are within the method linear range. Intra- and inter-day variability were 13.8% and 4.3% (at 15 ng mL-1 ) and 13.5% and 11.0% (at 85 ng mL-1 ), respectively (n = 3); inter-device variability was 9.6% (n = 10). CONCLUSIONS: Low inter-device variability makes these devices suitable for single use in a clinical setting, and the fast and robust method is suitable for therapeutic drug monitoring, where throughput and time-to-result are critical.

Single-use porous polymer thin-film device: A reliable sampler for analysis of drugs in small volumes of biofluids.

The response to the demand for biomedical testing on small volumes of biofluids has led to a range of new microsampling devices and related techniques. Simple cost-effective sampling devices are available, but most do not incorporate sample clean-up and necessitate extensive sample processing by the analyst. To address both cleanup and analyte stability, a porous polymeric thin film made of methacrylic acid (MAA) and ethylene glycol dimethacrylate (EGDMA) coated (5 × 18 mm2) on a stainless steel substrate was used for the extraction of seven tricyclic antidepressants (TCAs) from plasma spots, with analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Essential factors such as sample volume, extraction time, matrix effects, and the desorption process were investigated. The optimized method is comprised of a quick 3-min extraction from 10 µL of plasma, a wash (10 s in 1 mL of 1% aqueous triethylamine (TEA) to remove plasma matrix interferences, and 2-min desorption (200 µL of ACN with 0.1% formic acid (FA)). For the purpose of sample archiving, thin film devices containing extracted TCAs were stored for 30 days at room temperature and showed a consistent analyte recovery. Inter-device reproducibility was evaluated without internal standard (%RSD 8.2-19.3%), and using two methods of introducing a single deuterated internal standard (imipramine-D3) either prior to (%RSDs 5.6-13.9%) or after (%RSDs 4.9-10.2%) sample loading to the device. Although the intention of this study was to introduce a single use device for rapid and easy analysis, reusability showed the feasibility of 15 consecutive extractions using same device without any performance loss. The optimized method revealed excellent linearity (R2 > 0.99) in the range of 1-1000 ng mL-1, with good intra- and inter-day accuracy (81.4-118%) and precision (≤12%) in human plasma.

Biological matrix compatible porous thin film for quick extraction of drugs of abuse from urine prior to liquid chromatography-mass spectrometry analysis.

An efficient analytical method is developed using a porous sorptive polymer for thin film microextraction (PSP-TFME) of 8 model drugs from human urine samples. The analysis is conducted with ultra high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). The composition of the porous extraction phase, prepared on a stainless steel substrate, has been optimized for basic drugs of abuse and comprises methacrylic acid (MMA) as the monomer and ethylene glycol methacrylate (EGDMA) as the crosslinker. Factors influencing the analyte recovery and method precision (i.e., sample agitation, pH, extraction and washing time, desorption solvent and time) were assessed. The optimized method includes 5 min of direct immersion of the device into the sample, followed by a quick wash in water (1 min) to remove matrix interferences, and then 5 min in acidified methanol for analyte desorption. The extraction devices demonstrated acceptable inter-device variability (2.9-9.3 %RSD for 8 analytes and n = 10 devices) and no detectable difference between batches of devices (p > 0.05 for a 2-sample t-test). The analytical method was linear over a pharmacologically relevant range for each drug (i.e., 0.05-100 ng mL-1 for MDMA and methadone and 2.5-500 ng mL-1 for morphine with R2 varied from 0.9960 to 0.9996). A matrix effect study showed the devices have a high tolerance for complex variable biological matrices. The method also demonstrated excellent data accuracy in the range of 85.3-117.2% for intra-day assays and 88.8-117.9% for inter-day assays. The precision of the method was acceptable and in the range of 0.9-18.6% for intra- and 2.8-16.4% for inter-day assays, respectively.

Purification of Functional Gene Transfer Agents Using Two-Step Preparative Monolithic Chromatography.

Background: Gene transfer agents (GTAs) are phage-like particles that transfer cellular genomic DNA between cells. A hurdle faced in studying GTA function and interactions with cells is the difficulty in obtaining pure and functional GTAs from cultures. Materials and Methods: We used a novel two-step method for purification of GTAs from R. capsulatus by monolithic chromatography. Results: Our efficient and simple process had advantages compared to previous approaches. The purified GTAs retained gene transfer activity and the packaged DNA could be used for further studies. Conclusions: This method is applicable to GTAs produced by other species and small phages, and could be useful for therapeutic applications.

Micro-gel thin film molecularly imprinted polymer coating for extraction of organophosphorus pesticides from water and beverage samples.

Molecularly imprinted polymers (MIPs) have become an important class of materials for selective and efficient adsorption of target analytes. Despite versatility of MIPs for fabrication in numerous formats, these materials have been primarily reported as solid phase extraction packing materials. An effective thin film MIP prepared on stainless steel substrate is reported here for high throughput enrichment of organophosphorus pesticides (OPPs) from water and beverage samples followed by liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. The key factors controlling performance as well as best practices for optimized fabrication of thin film MIPs are presented. A pseudo-phase diagram is introduced to evaluate and predict the effect of the ratio of porogen (solvent, 1-octanol) volume to relative crosslinker mass on the desired polymer features (i.e., porosity, surface area, capacity, and selectivity). At low porogen ratios, a macroporous polymer with insignificant selectivity is formed, whereas at high porogen ratios a micro-gel polymer with superior selectivity towards targets is obtained. The porosity and morphology determined with nitrogen adsorption and scanning electron microscopy were attributed to specific regions in the pseudo-phase diagram. Other factors influencing selectivity and stability of the polymer, such as type of the template and its ratios with monomer (methacrylic acid) and crosslinker (ethylene glycol dimethacrylate) were optimized. The prepared thin film MIPs were characterized using adsorption isotherms and adsorption kinetics, and evaluated for matrix effects (high humic acid content) and cross-reactivity in presence of other pesticides and pharmaceuticals. The optimized method provided limits of quantitation (LOQs) ranged from 0.002 to 0.02 ng mL-1 in water and from 0.095 to 0.48 ng g-1 in apple juice. Regarding inter-device variability (CV∼10% without normalization), excellent linearity (R2 > 0.99), satisfactory accuracies (90-110%) and precisions (<15%) were obtained.

Thin film molecularly imprinted polymer (TF-MIP), a selective and single-use extraction device for high-throughput analysis of biological samples.

Enhancing selectivity, reducing matrix effects and increasing analytical throughput have been the main objectives in the development of biological sample preparation techniques. A thin film molecularly imprinted polymer (MIP) is employed for extraction and analysis of tricyclic antidepressants (TCAs) as a model class of compounds in human plasma for the first time to reach the abovementioned goals. The thin film MIPs prepared on a metal substrate can be used directly for extraction from biological matrices with no sample manipulation steps and no pre-conditioning. This method was validated with good linearity (R2 > 0.99 in 1.0-500.0 ng mL-1 range), excellent accuracy (90% -110%) and precision (RSD % value less than 15%) in pooled human plasma samples (N = 3). The limits of quantitation (LOQ) for TCAs in plasma samples were between 1.0-5.0 ng mL-1 which are lower than the therapeutic ranges of these drugs. Kinetic and isotherm studies showed the superior performance of MIP sorbent compared to a non-imprinted polymer (NIP) sorbent in extracting TCAs from a bovine serum albumin (BSA) solution. The optimized and validated method for pooled human plasma was utilized for monitoring the concentration of TCAs in three patient samples who had been prescribed TCAs. These selective single-use thin film extraction devices are promising for efficient and fast procedures for analyzing biological samples.

Porous thin-film molecularly imprinted polymer device for simultaneous determination of phenol, alkylphenol and chlorophenol compounds in water.

A porous water-compatible molecularly imprinted polymer (MIP) coating using catechol as a pseudo-template and a water-soluble functional monomer (4-vinyl benzoic acid) with ethylene glycol dimethacrylate as the crosslinker was developed for extraction of phenols from environmental water samples. The MIP devices were combined with ultra high performance liquid chromatography with a photodiode array detector (UHPLC-PDA) suitable for the simultaneous determination of trace levels of phenolic compounds with a wide range of polarities -phenol, alkylphenols and chlorophenols- in seawater and produced water. Parameters that influence extraction efficiency (salinity, pH, polymer mass, desorption solvent, and desorption time) were optimized to give method detection limits (LOD) ranging from 0.1 to 2 µg L-1 and linearity (R2>0.99) over at least three orders of magnitude for the hydrophobic phenols (e.g., 0.5-1000 µg L-1 for 2,4,6-trichlorophenol) and ~2 orders of magnitude for the light phenols (e.g., 10-120 µg L-1 for phenol, 5-120 µg L-1 for methylphenols and 2-chlorophenol, 0.5-120 µg L-1 3-methyl-4-chlorophenol and 2,4-dichlorophenol). The recoveries from authentic spiked samples ranged from 85 to 100% with %RSDs of 0.2-14% for seawater and 81-107% with %RSD of 0.1-11% for produced water. The resulting MIP-based extraction requires no pre-conditioning of the sorbent, and because the required sample size is small and sample manipulation is limited, the method is easy to multiplex for high throughput sample processing.

Assessment of cross-reactivity in a tailor-made molecularly imprinted polymer for phenolic compounds using four adsorption isotherm models.

Cross-reactivity is an important feature of molecularly imprinted polymers (MIPs), and is central to successful use of a pseudo-template in molecular imprinting. The adsorption and cross-reactivity of a molecularly imprinted polymer (MIP) designed for recognition of phenols from water was assessed using four different isotherm models (Langmuir (LI), Freundlich (FI), Langmuir-Freundlich (L-FI), and Brunauer, Emmett, and Teller (BET)). The L-FI model succeeded in explaining the cross-reactivity behavior through the total number of binding sites, the affinity constants and heterogeneity indices of the small phenols (phenol (ph), 2-methylphenol (2-MP), 3-methylphenol (3-MP), 2-chlorophenol (2-CP), 2,4-dimethylphenol (DMP), 2,4-dichlorophenol (DCP), 4-chloro-3-methylphenol (CMP)) with evidence that the phenols compete for binding sites based on their hydrophobicity as well as π-π, π-σ and dipole-dipole intermolecular forces. The recognition of the large phenols (2,4,6-trichlorophenol (TCP), pentachlorophenol (PCP), 4-teroctylphenol (4-OP), 4-nonylphenol (4-NP), which have much higher binding affinities than the smaller phenolic compounds, was explained with the BET isotherm model that predicts that multiple layers adsorb to the adsorbed monolayer. The adsorption behavior with MIPs is also shown to be superior to corresponding non-imprinted polymers and applicability of MIPs for trace analysis is highlighted.

Comparison of Four Adsorption Isotherm Models for Characterizing Molecular Recognition of Individual Phenolic Compounds in Porous Tailor-Made Molecularly Imprinted Polymer Films.

A molecularly imprinted polymer (MIP) film using catechol as the template was designed for adsorption of a range of phenols from water. Four different isotherm models (Langmuir (LI), Freundlich (FI), Langmuir-Freundlich (L-FI), and Brunauer, Emmett, and Teller (BET)) were used to study the MIP adsorption of five phenolic compounds: phenol (Ph), 2-methylphenol (2-MP), 3-methylphenol (3-MP), 2-chlorophenol (2-CP), and 4-teroctylphenol (4-OP). Each model was evaluated for its fit with the experimental data, and key parameters, including a number of binding sites and binding site energies, were compared. Though the LI, L-FI, and BET models showed good agreement for estimation of the number of binding sites and affinity for most adsorbates, no single model was suitable for all. The LI and L-FI models gave the best fitting statistics for the Ph, 2-MP, 3-MP, and 2-CP. The recognition of 4-OP, which has much higher binding affinities than the smaller phenolic compounds not attributable to hydrophobicity alone, was explained only by the BET model, which indicates the formation of multilayers. The BET model failed only with phenol. MIPs also showed higher adsorption capacities and improved homogeneity over the analogous non-imprinted polymers.

Molecularly imprinted polymer thin-film as a micro-extraction adsorbent for selective determination of trace concentrations of polycyclic aromatic sulfur heterocycles in seawater.

A tailor-made porous molecularly imprinted polymer (MIP) thin-film was prepared by in situ photo-radical polymerization on a glass slide and used as a microextraction adsorbent. Detection was carried out using gas chromatography-mass spectrometry (GC-MS) to afford a method suitable for the selective determination of trace concentrations of polycyclic aromatic sulfur heterocycles (PASHs) in seawater. PASHs are one of the most problematic aromatic organic pollutants, as they are considered more persistent and toxic compared to other analogous aromatic compounds in the environment. The optimized thin-film consisted of a 2-thiophenecarboxaldehyde pseudo-template with 1-vinylimidazole (1-Vim) as the functional monomer, bisphenol A dimethacrylate (BPADMA) as the cross-linker, acetonitrile as the porogen, and polyethylene glycol to boost porosity through formation of interpenetrating polymer networks. The adsorption behaviours of the thin-film, including adsorption kinetics, binding isotherms, and selectivity of MIP thin-film were investigated in detail. The highest imprinting factors (2.3-3.0) and adsorption capacity for targeted PASHs were achieved at a template:monomer:cross-linker ratio of 1:4:8. The method with no sample or film pretreatment showed very good reproducibility for the extraction of PASHs from spiked seawater samples (RSDs ≤ 6.0%, n = 3), was linear (R2 > 0.9960) over a range of 0.5-40 µg L-1, and gave limits of detection n the range of 0.029-0.166 µg L-1.

Magnetic molecularly imprinted polymers prepared by reversible addition fragmentation chain transfer polymerization for dispersive solid phase extraction of polycyclic aromatic hydrocarbons in water.

Magnetic molecularly imprinted polymers (MMIPs) combine nanotechnology and molecular imprinting technology to offer selective and tunable enrichment for water analysis. In this paper, a selective sorbent was prepared by surface polymerization onto magnetic Fe3O4@SiO2 nanoparticles through reversible addition fragmentation chain transfer (RAFT) polymerization. The MMIPs were used for dispersive solid phase extraction (DSPE) of 16 PAHs as priority pollutants in aqueous matrices. After preconcentration, the analysis was performed using gas chromatography with an atmospheric pressure chemical ionization-tandem mass spectrometry (APGC-MS/MS). The extraction method is based on the dispersion of MMIPs in an aqueous sample using an ultrasonic bath which provides rapid equilibrium of analytes between the sorbent and sample solution. The enriched analytes were retrieved by collecting MMIP particles and desorbed into an organic solvent before instrumental analysis. A design of experiment (DOE) approach was applied to optimize several extraction parameters including the mass of MMIPs, the sample volume, salt addition, collection time, desorption volume, and desorption time. A fractional factorial design (FFD) (26-2) was performed to assess the influence of the selected factors on the extracted amount of analytes. The most effective factors including the mass of MMIPs, the volume of sample solution, and salt content was further investigated using central composite design (CCD) and yielded quadratic models between dependent and independent variables. The optimum conditions of DSPE obtained by desirability function (DF) were employed for preconcentration of PAHs in water samples. The evaluation showed that the MMIPs provide higher extraction efficiency compared to nanoparticles such as Fe3O4, Fe3O4@SiO2 and non-imprinted polymer, demonstrating the creation of selective recognition binding sites at the surface of magnetic nanoparticles. The LODs and LOQs ranged from 1 to 100 pg mL-1 and 2 to 200 pg mL-1, respectively. Finally, the MMIP-DSPE method was successfully applied for preconcentration and trace quantification of PAHs in real samples such as produced water and river water samples.

Single-use porous thin film extraction with gas chromatography atmospheric pressure chemical ionization tandem mass spectrometry for high-throughput analysis of 16 PAHs.

The need for high throughput, reliable analytical methods for environmental analysis has driven our development of novel sampling technologies that can be used in microextraction devices and integrated into chromatographic systems for fast analysis. Here we report a new method of water analysis for 16 EPA priority polycyclic aromatic hydrocarbons (PAHs) that relies on a tailor made porous polymeric film for extraction with analysis by gas chromatography with atmospheric pressure chemical ionization-tandem mass spectrometry (APGC-MS/MS). The extraction device is user friendly, single-use and gives exhaustive extraction from a relatively small volume (20 mL). The films show good stability, with excellent analytical performance. Critical factors affecting the extraction efficiency such as desorption solvent, desorption time, extraction agitation, and extraction time were studied and optimized. These thin films are cost effective and efficient for single use analysis, but carry-over studies showed that the films can be reused at least 10 times without extensive washing and with no loss in performance. The 16 PAHs were measured with excellent limits of detection ranging from 1 pg mL-1 for BaA to 100 pg mL-1 for Flu and linearity (R2 > 0.997) over the 1-50,000 pg mL-1 concentration range. This high throughput method (1-h extractions, which can be completed simultaneously) showed good reproducibility (<20%) with recoveries in the range of 19.0-40.6% and concentration factors varying between 37.9 and 81.1. Analysis of real seawater and river water samples using matrix-matched calibration in synthetic seawater and river water showed only small matrix effects maintaining high sensitivity (LODs:1-100 pg mL-1), demonstrating that the films are suitable for analysis of real samples without the need for standard addition.

A critical review of molecularly imprinted polymers for the analysis of organic pollutants in environmental water samples.

Molecularly imprinted polymers (MIPs) with tailor-made recognition sites are used in water analysis for selective sample pretreatment before quantitation. The exceptional performance of MIPs with reduced interferences and matrix effects during sample preparation has resulted in selective and precise analytical methods by enhancing chromatographic separation and detection. MIPs are fabricated using a varying range of synthetic procedures and used as the adsorptive phase in solid phase extraction (SPE), dispersive solid phase extraction (DSPE), solid phase microextraction (SPME), stir bar sorptive extraction (SBSE), and membrane-based extraction techniques. In this paper, a comprehensive review of MIP technologies reported in the literature for water analysis is provided. MIPs are critically evaluated using key performance criteria, such as adsorption capacity, imprinting factor, chromatographic retention factor, and cross-selectivity. The recent advances of MIP technologies including the preparation protocols, applications and developments are discussed. Additionally, the performance of MIPs which can be improved by optimizing the composition of the polymeric network is reviewed regarding the characteristics of rebinding medium. The limitations of MIPs for water analysis, especially restricted selectivity for water soluble analytes, material wettability, and MIP inhomogeneity are discussed by providing the possible solutions. Finally, some novel applications and prospects for online, rapid and direct analysis of environmental samples using MIPs are included.

High throughput direct analysis of water using solvothermal headspace desorption with porous thin films.

Sample preparation has remained a bottleneck in analysis of biological and environmental samples. Thus, microextraction techniques to reduce time, cost, labor, and environmental impacts as compared to traditional solid phase or liquid-liquid extractions are appealing. In this work, a high throughput extraction method coupled with a novel desorption technique has been developed for the analysis of eight regulated PAHs in water. The targeted analytes were extracted by thin film microextraction (TFME) using single-use sorbents. The enriched analytes on thin films were directly introduced into a gas chromatography with a flame ionization detector (GC-FID) through solvothermal headspace desorption (ST-HD). The desorption of analytes was accelerated by adding a small volume of solvent into the headspace vial. The parameters that influence desorption, such as type and volume of solvent, oven temperature, and desorption time, were studied. As well, the key parameters (stirring rate, extraction time, and salt content) for TFME of PAHs from water were assessed and optimized. Reusability and durability of the film and background noise due to polymer decomposition were also assessed. The method was validated using standards in 3.5% aqueous NaCl. The limits of detection (LODs) were between 0.2 and 2.0 ng mL-1, with linear ranges of 0.4-200.0 ng mL-1 with R2 > 0.99, and satisfactory accuracy and repeatability at three concentrations (low, mid, and high) within the linear range of the calibration curves. The calibration curves were also assessed for suitability as a matched matrix in the analysis of PAHs in a seawater sample. The technique was also applied for determination of PAHs in a produced water sample without the need for pretreatment and filtration of the sample. Although the complexity of produced water required the use of standard addition, we demonstrated that this approach is a useful tool for the analysis of complicated environmental samples.

Selective determination of semi-volatile thiophene compounds in water by molecularly imprinted polymer thin films with direct headspace gas chromatography sulfur chemiluminescence detection.

Water-compatible molecularly imprinted polymer (MIP) thin films are coupled with headspace gas chromatography sulfur chemiluminescence detection (HS-GC-SCD) to create a new approach for the determination of trace concentrations of thiophene compounds in water samples. Thiophene compounds are persistent, typically petrogenic, organic pollutants of concern due to their potential for biomagnification and bioaccumulation, mutagenicity, and carcinogenicity in terrestrial and aquatic fauna. Identification and quantitation in water, particularly following oil spills, is a priority. Following adsorption of the thiophenes to the MIPs, the MIP-bound analytes are analyzed directly by HS-GC-SCD, with minimal sample manipulation and virtually no organic solvent. Calibration curves of spiked seawater were linear from 5 µg L-1 to 100 µg L-1 and limits of detection (LOD) were in the range of 0.24-0.82 µg L-1. Low matrix effects were observed in the analysis of thiophene compounds in seawater making the method suitable for use in fresh and saline waters without modification. Acceptable reproducibility was obtained for analysis of thiophene compounds from spiked seawater samples at RSDs ≤7.0% (n = 3).

Tandem mass spectrometry determination of the putative structure of a heterogeneous mixture of Lipid As isolated from the lipopolysaccharide of the Gram-negative bacteria Aeromonas liquefaciens SJ-19a.

RATIONALE: We report herein the electrospray ionization mass spectrometry (ESI-MS) and low-energy collision-induced dissociation tandem mass spectrometry analysis (CID-MS/MS) of a mixture of lipid As isolated from the rough lipopolysaccharide (LPS) of the mutant wild strain of the Gram-negative bacteria Aeromonas liquefaciens (SJ-19a, resistant) grown in the presence of phages. The interaction between the phages and the Gram-negative bacteria regulates host specificity and the heterogeneity of the lipid A component of the LPS. METHODS: The heterogeneous mixture of lipid As was isolated by the aqueous phenol method from the LPS of the rough wild strain of Gram-negative bacteria Aeromonas liquefaciens (SJ-19a). Hydrolysis of the LPS was with 1% acetic acid, and purification was by chromatography using Sephadex G-50 and Sephadex G-15. ESI-MS and low-energy CID-MS/MS analyses were performed with a triple-quadrupole (QqQ) and a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. RESULTS: Preliminary analysis of the lipid As mixture was conducted by ESI-MS in the negative ion mode and the spectrum obtained suggested that the lipid A SJ-19a was composed of a heterogeneous mixture of different lipid A molecules. CID-MS/MS experiments confirmed the identities of the various mono-phosphorylated ß-D-GlcpN-(1→6)-α-D-GlcpN disaccharide entities. This lipid As mixture was asymmetrically substituted with fatty acids such as ((R)-14:0(3-OH)), (14:0(3-(R)-(O-12:0)) and (14:0(3-(R)-O-(14:0)) located on the O-3, O-3', N-2 and N-2' positions, respectively. CONCLUSIONS: Low-energy collision-induced dissociation tandem mass spectrometry in-space (QqQ-MS/MS) and in-time (FTICR-MS/MS) allowed the exact determination of the fatty acid acylation positions on the H2 PO3 →4-O'-ß-D-GlcpN-(1→6)-α-D-GlcpN disaccharide backbones of this heterogeneous mixture of lipid As , composed inter alia of seven different substituted lipid As , formed from the incomplete biosynthesis of their respective LPS.

A MALDI-TOF MS analysis study of the binding of 4-(N,N-dimethylamino)pyridine to amine-bis(phenolate) chromium(III) chloride complexes: mechanistic insight into differences in catalytic activity for CO2/epoxide copolymerization.

Amine-bis(phenolato)chromium(III) chloride complexes, [LCrCl], are capable of catalyzing the copolymerization of cyclohexene oxide with carbon dioxide to give poly(cyclohexane) carbonate. When combined with 4-(N,N-dimethylamino)pyridine (DMAP) these catalyst systems yield low molecular weight polymers with moderately narrow polydispersities. The coordination chemistry of DMAP with five amine-bis(phenolato)chromium(III) chloride complexes was studied by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The amine-bis(phenolato) ligands were varied in the nature of their neutral pendant donor-group and include oxygen-containing tetrahydrofurfuryl and methoxyethyl moieties, or nitrogen-containing N,N-dimethylaminoethyl or 2-pyridyl moieties. The relative abundance of mono and bis(DMAP) adducts, as well as DMAP-free ions is compared under various DMAP : Cr complex ratios. The [LCr](+) cations show the ability to bind two DMAP molecules to form six-coordinate complex ions in all cases, except when the pendant group is N,N-dimethylaminoethyl (compound ). Even in the presence of a 4 : 1 ratio of DMAP to Cr, no ions corresponding to [L3Cr(DMAP)2](+) were observed for the complex containing the tertiary sp(3)-hybridized amino donor in the pendant arm. The difference in DMAP-binding ability of these compounds results in differences in catalytic activity for alternating copolymerization of CO2 and cyclohexene oxide. Kinetic investigations by infrared spectroscopy of compounds 2 and 3 show that polycarbonate formation by 3 is twice as fast as that of compound 2 and that no initiation time is observed.

New pressure-assisted sweeping on-line preconcentration for highly polar environmentally relevant nitrosamines: Part 2. Cationic and anionic surfactants with zero-flow capillaries.

We recently introduced a pressure-assisted sweeping-reversed migration-EKC (RM-EKC) method for preconcentration of neutral polar N-nitrosamines with low affinity for the micellar phase. The type of surfactant and phase ratio are dominant factors in dictating the magnitude of interactions between analyte and micellar phase, thus four surfactants (anionic and cationic) with a range of functionalities (SDS, ammonium perfluorooctanoate (APFO), bile salts, and cetyltrimethylammonium chloride (CTAC)) were evaluated for sweeping-RM-EKC of highly polar N-nitrosamines. All gave acceptable results for sweeping-RM-EKC when used in high concentrations (≥200 mM) with low EOF. While no single surfactant was superior by all measures, all but the bile salts had useful performance characteristics. APFO showed the narrowest peak widths and highest number of theoretical plates, though two species co-migrated at all concentrations (25-300 mM); SDS and the cationic surfactant CTAC also showed good separation characteristics and could resolve all peaks, but CTAC had wider separation window. Various types of capillaries coated for EOF control were compared for use with anionic and cationic surfactants. A commercial zero-EOF capillary coated with a polymer bearing sulfonic acid functional groups showed superior EOF suppression and reproducibility of migration time with all surfactants.

Development of molecularly imprinted polymer in porous film format for binding of phenol and alkylphenols from water.

Molecularly imprinted polymers (MIPs) were fabricated on glass slides with a "sandwich" technique giving ~20 µm thick films. Methanol/water as a solvent, and polyethyleneglycol and polyvinylacetate as solvent modifiers, were used to give a porous morphology, which was studied with scanning electron microscopy and gravimetric analysis. Various MIPs were synthesized through non-covalent imprinting with phenol as the template; itaconic acid, 4-vinylpyridine, and styrene as monomers; ethylene glycol dimethacrylate, triethylene glycol dimethacrylate, and pentaerythritol triacrylate (PETA) as cross-linkers. Binding and imprinting properties of the MIPs were evaluated based on phenol adsorption isotherms. Since phenol has only one weakly acidic hydroxyl group and lacks unique structural characteristics necessary for binding specificity, the preparation of selective MIPs was challenging. The recognition of phenol via hydrogen bonding is suppressed in water, while hydrophobic interactions, though promoted, are not specific enough for highly-selective phenol recognition. Nevertheless, the styrene-PETA MIP gave modest imprinting effects, which were higher at lower concentrations (Imprinting Factor (IF) = 1.16 at 0.5 mg·L(-1)). The isotherm was of a Freundlich type over 0.1-40 mg·L(-1) and there was broad cross-reactivity towards other structurally similar phenols. This shows that phenol MIPs or simple adsorbents can be developed based on styrene for hydrophobic binding, and PETA to form a tighter, hydrophilic network.

New pressure-assisted sweeping on-line preconcentration for polar environmentally relevant nitrosamines: Part 1. sweeping for polar compounds and application of auxiliary pressure.

Typically sweeping reversed migration EKC (RM-EKC) is used for online enrichment and separation of neutral compounds in CE, however sweeping is not usually suitable for highly polar neutral compounds due to the lack of strong interaction with micellar phase. Since acidic BGE or coated capillaries (BGE pH 2-8) are used to virtually eliminate the EOF, migration of neutral analytes is only through association with the micelles with relatively slow electrophoretic mobility. To decrease the long analysis times that result, an auxiliary pressure can be applied, which also serves to avoid the associated band broadening. In this study, we have modified a commercially available CE instrument to perform pressure-assisted sweeping. The apparatus described can be used to precisely control the application of pressure, and therefore direction and magnitude of bulk flow in the capillary. This modification allows us to employ longer capillaries and capillaries with larger internal diameter to increase the sensitivity. An optimized method was used for the analysis of a group of seven N-nitrosamines that have been widely reported in environmental samples and good concentration factors of up to 34 were achieved. When a coated capillary is employed, this method is effective even at neutral pH, making it broadly applicable.