A computational and experimental investigation of the interaction between the template molecule and the functional monomer used in the molecularly imprinted polymer

A computational approach to screening monomer for preparing molecularly imprinted polymer (MIP) was proposed, using the binding energy, ΔE, of a template molecule and a monomer as a measure of their interaction. For a specified template molecule, a monomer of higher ΔE is suitable for preparing the MIP. To examine the validity of this approach, theophylline (THO) was chosen as the template molecule and methacrylic acid (MAA), acrylamide (AA) and 2-(trifluoromethyl)acrylic acid (TFMAA) were as the functional monomers, respectively. Density functional theory (DFT) at B3LYP/6-31+G**//B3LYP/3-21G level was used to calculate ΔE. It was shown that TFMAA gave the largest ΔE while AA gave the smallest. The details of the interaction between the THO with these monomers were also given by this computing approach. The adsorption of THO on the MIP synthesized using different monomers was studied. The MIP synthesized using TFMAA as monomer showed the highest selectivity to THO while the MIP from AA gave the lowest, as predicted from the ΔE calculation. ¹H NMR spectroscopy showed that, compared to MAA and AA, a stronger H-bond interaction is formed between TFMAA and THO. FT-IR analysis of the MIPs prepared using these three monomers confirmed the existence of CO and OH groups, which forms H-bond with THO. The results described above have given an insight into the interaction between THO and the monomers, and shown the use of ΔE to facilitate the selection of monomers for the synthesis of MIP.     

Solvent effects in the preparation of molecularly imprinted polymers for melatonin using N-propionyl-5-methoxytryptamine as the pseudo template

To clarify the role of diluents in the preparation of molecularly imprinted polymers utilizing only hydrogen bonding, we investigated the effects of diluents by using different solvents. Melatonin (N-acetyl-5-methoxytryptamine), an amide bond and indole ring-containing hormone was chosen as the target molecule. N-Propionyl-5-methoxytryptamine was used as the pseudo template, methacrylic acid as the functional monomer, and solvents were used as diluents. Interactions between the template, the functional monomer, melatonin, and the solvents, were observed by ¹H NMR spectroscopy. The polymers were evaluated by high-performance liquid chromatography. The results suggest the hydrogen bonding-acceptor capacity of the solvent is the most important factor in the preparation of molecularly imprinted polymers for hydrogen bonding-donating molecules. Hydrogen bonding between the template, the functional monomer, and solvent can be estimated from the chemical shifts in ¹H NMR spectra of those molecules in the solvent.     

Synthesis and characterization of molecularly imprinted polymers for selective solid-phase extraction of pseudoephedrine

Molecular imprinted solid-phase extraction (MISPE) is a well known technique for the selective extraction and pre-concentration of analytes, are present at low levels in chemically complex materials. Herein, water-soluble, molecularly imprinted polymers (MIP) were prepared for solid-phase extraction of pseudoephedrine hydrochloride (PSE), which was monitored at 256 nm by the UV spectroscopy. MISPE conditions were optimized to allow the selective and determination of PSE in aqueous samples and composite materials, such as biological fluids and human urine. MIP was prepared by precipitation polymerization method, using methacrylic acid as a functional monomer and ethylene glycol dimethacrylate as a cross-linking agent in either acetonitrile or chloroform. The results suggest that the obtained MISPE exhibits high affinity for PSE, and the imprinted polymer demonstrates much higher efficiency than a non-imprinted polymer (NIP). The imprinting-induced extraction was confirmed by the determination of recovery values for NIP (4%) and MIP (80%) polymers, respectively. The binding capacity of the MIP for PSE was found of 47.6 mg g⁻¹.     

三唑酮分子印迹预组装体系的分子模拟与吸附性能

以三唑酮为模板分子, 以丙烯酰胺(AM)、 丙烯酸(AA)、 甲基丙烯酸(MAA)和三氟甲基丙烯酸(TFMAA)为功能单体预组装了分子印迹聚合物体系, 采用半经验法和从头算法, 利用Hyperchem软件模拟了三唑酮与4种功能单体所组成的分子印迹预组装体系的构型、 能量、 反应配比及复合反应的结合能, 选择复合物结合能最高的功能单体用于分子印迹聚合物的合成. 采用密度泛函方法计算了模板与单体在不同致孔剂中的溶剂化能. 结果表明, 三唑酮与三氟甲基丙烯酸所形成复合物的作用力最强, 在非极性溶剂中溶剂化能最弱. 由预组装体系的差示紫外光谱法研究发现, 一分子三唑酮可与两分子三氟甲基丙烯酸在氯仿中形成氢键复合物, 与分子模拟的结果一致. 在最佳模拟条件下, 合成了三唑酮的印迹聚合物, 利用吸附等温线Langmuir和Freundlich模型研究了印迹聚合物的吸附行为及识别机理. 上述方法对于分子印迹体系的筛选及分子印迹聚合物性能的预测有重要的意义.     

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

A 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.

Preparation and characterization of molecularly imprinted organic–inorganic hybrid materials by sol–gel processing for selective recognition of ibuprofen

This work adopted semi-covalent imprinting to prepare molecularly imprinted polymers (MIP) with ibuprofen, a non-steroidal anti-inflammatory drug, as template by sol–gel processing, which is characterized by both the high affinity of covalent binding and the mild operation conditions of non-covalent rebinding. A functional monomer, which was used to synthesize the monomer-imprinted molecule complex, was prepared by multi-step synthesis for the first time. MIP was characterized by Fourier transform IR spectrum and nitrogen adsorption. Thin-layer chromatography separation was used to evaluate the specific molecular recognition ability of MIP. In addition, dynamic and thermodynamic studies on MIP imprinting ibuprofen were undertaken. The results of equilibrium rebinding experiments showed that MIP exhibited good adsorption capacity for ibuprofen. Scatchard analysis illustrated that the template-polymer system shows only one-site binding behavior with a dissociation constant of 1.84 mmol L^?1. Dynamic adsorption exhibited pseudo-second-order kinetics. The positive value of ΔH^θ and the negative values of ΔG^θ demonstrated that the binding system for MIP is endothermic and spontaneous.     

齐墩果酸分子印迹聚合物预组装体系的分子模拟及聚合物制备

以齐墩果酸(OA)为模板分子,三氟甲基丙烯酸(TFMAA)、α-甲基丙烯酸(MAA)、丙烯酰胺(AM)、4-乙烯基吡啶(4-VP)为功能单体,三氯甲烷、四氢呋喃、乙醇、甲醇和丙酮为溶剂,基于量子化学密度泛函理论(DFT)和ONIOM方法,采用Gaussian09软件模拟计算了模板分子与不同功能单体的印迹聚合物预组装体系的构型,探讨了模板分子与功能单体在不同印迹比例时所形成复合物的成键情况以及反应过程中的结合能,并采用自洽反应场极化连续模型(CPCM)计算了功能单体与模板分子在不同溶剂中的溶剂化能。结果表明,TFMAA与模板分子OA以1:1摩尔比形成复合物的结合能ΔE最高(-70.99kJ·mol~(-1)),结构最稳定,模板分子和功能单体在三氯甲烷中的溶剂化能最小。同时,采用实验方法验证模拟结果,并利用扫描电镜、傅里叶红外光谱仪和静态吸附实验对印迹聚合物的形貌、化学基团和吸附性能等进行表征。结果表明,模拟结果与实验结果完全一致,计算机模拟对分子印迹体系的筛选和机理研究提供了理论依据。     

Molecularly imprinted polymer for metsulfuron-methyl and its binding characteristics for sulfonylurea herbicides

A molecularly imprinted polymer (MIP) was prepared using metsulfuron-methyl (MSM) as the template molecule. A combinatorial protocol has been employed to optimize the polymer in terms of the kind and relative amounts of functional and cross-linking monomers. A copolymer of 2-(trifluoromethyl)acrylic acid (TFMAA) and divinylbenzene (DVB) showed the highest binding capacity for MSM. The binding characteristics of the imprinted polymers and MSM were evaluated in various solvents using equilibrium binding experiments. The results showed that the MIP binds MSM only in dichloromethane, which was used as the porogen during polymerization. Scatchard plot analysis revealed that two classes of binding sites were formed in the imprinted polymer with dissociation constants of 32.3 μmol l⁻¹ and 1.7 mmol l⁻¹, respectively. The specificity of the imprinted polymer was investigated by binding assays using MSM and other structurally related sulfonylurea herbicides. The results indicated that the imprinted polymer showed a marked selectivity for MSM.     

加速溶剂萃取快速洗脱印迹聚合物中的模板分子

通过优化实验条件,选择洗脱温度80℃、加热时间5min、萃取压力10.4MPa、洗脱溶剂为300mL的甲醇/乙酸(90∶10,V/V),静态萃取时间8min、吹扫时间100s,对1.000g尼古丁印迹聚合物中的模板分子进行连续6次的萃取洗脱,洗脱效率达94.2%,模板渗漏量仅为9.8μg/L,萃取时间<70min。将2000mg洗脱后的印迹聚合物颗粒装填于3mL的聚丙烯固相萃取小柱中,用10mL甲醇/乙酸(90∶1,V/V)淋洗小柱,用高效液相色谱检测淋洗液中的尼古丁,获得模板的渗漏量为9.8μg/L。     

Application of umbelliferone molecularly imprinted polymer in analysis of plant samples

The molecularly imprinted polymers (MIPs) were synthesised and the influence of the type of porogen, the nature of sample solvent, and the binding capacity of material were tested by high-performance liquid chromatography (HPLC). Umbelliferone was used as the template for imprint formation. Methacrylic acid was used as the monomer and acetonitrile, ethanol, and chloroform as porogen. Non-imprinted polymers (NIPs) were prepared by the same procedure. The highest value of the specific binding capacity (269 μg of umbelliferone per 100 mg of polymer) was obtained for polymers prepared in chloroform as porogen and methanol/water (φ _r = 1: 1) as the sample solvent. The group-selective MIP was used as sorbent for the SPE pre-treatment of umbelliferone from plant extracts prior to HPLC analysis. Analysis of the spiked samples showed good recoveries (> 77 %). The limit of detection, limit of determination, and repeatability of the method were also calculated.     

Study of the properties of molecularly imprinted polymers by computational and conformational analysis

In this paper, a simplified model was set up to give an insight into the properties of molecularly imprinted polymer (MIP) at molecular level using MMFF94 force field. Based on our model, the interaction energies (ΔEs) between monomers and template or its analogues were calculated, and the most possible conformations of template or its analogues interacting with monomers in the molar ratio 1/4 were found. The obtained results using the computational and conformational analysis showed that large ΔE meant more activity sites in the cavities in the resultant polymer giving high affinity and good selectivity, leading to a large imprinting factor and when the ΔE differences were small, the imprinting factors were mainly determined by the activity sites. These were well consistent with the experimental results, which confirmed the validity of the model and method proposed that were believed to benefit screening molecularly imprinted systems rapidly in an experiment-free way instead of trial-and-error approach. Considering the affinity and selectivity, 2,6-bisacrylamide pyridine was predicted to be the optimal monomer used to prepare paracetamol MIP for application in quantification of drugs from the ΔE and possible activity sites.     

反乌头酸分子印迹聚合物微球的制备及其分子识别功能

以乙腈为分散剂,采用沉淀聚合法合成了反乌头酸分子印迹聚合物微球。研究了合成反应条件对聚合物形貌的影响,发现聚合前主客体氢键络合物和功能单体氢键低聚体是控制微球形成及其粒径大小的关键因素。通过振荡吸附法对聚合物的结合特性进行了评价,发现印迹聚合物微球对模板分子的识别选择性优于块状印迹聚合物和非印迹聚合物。     

Preparation and Characterization of Trans‐Resveratrol Imprinted Polymers

Abstract

In order to selectively extract trans‐resveratrol from Chinese herbs, molecularly imprinted polymers (MIPs) were prepared with trans‐resveratrol as the template molecule. The influences of porogenic solvents and functional monomers on the recognition properties of the polymer were studied. The MIP, which was prepared in acetone using 4‐vinylpyridine as functional monomer, displayed good affinity and recognition property for the template molecule. This indicates that the 4‐vinylpyridine can form hydrogen‐bonding or ionic interaction with trans‐resveratrol. Experimental result also indicated that the MIP column can separate trans‐resveratrol from matrix components in the Polygonum cuspidatum extract.     

Sulfamethazine and Sulfadimethoxine Separation Strategies Based on Molecularly Imprinted Adsorbents

Abstract

The synthesis of molecularly imprinted polymer (MIP) as a stationary phase of high‐performance liquid chromatography (HPLC), for the efficient determination of sulfamethazine and sulfadimethoxine in tablets is reported. The polymers were prepared by a noncovalent method with sulfamethazine as the template, methacrylic acid as the functional monomer and ethylene glycoldimethacrylate as the cross‐linker in the presence of chloroform as the solvent. The retention time of sulfamethazine and sulfadimethoxine were approximately 5.2±0.2 and 10.3±0.5 min, respectively. In order to compare the chromatographic data from the stationary phase, retention factor (k) and separation factors (α) were given. The values of α were 2.05～2.17 showed that the MIP was able to recognize structurally subtle differences from the template molecule.

The MIP was successfully applied to commercial tablet analysis and the result showed a good recovery with 99 and 98% for sulfamethazine and sulfadimethoxine.     

Synthesis and Evaluation of Molecularly Imprinted Polymers as Sorbents for Selective Extraction of Coumarins

Coumarin, 7-hydroxycoumarin and dicoumarol molecularly imprinted polymers (MIP) were synthesized by bulk polymerization. Methacrylic acid and 4-vinylpyridine were tested as functional monomers and methanol, ethanol, acetonitrile, toluene and chloroform were tested as porogens. The binding capabilities of the imprinted polymers were assessed by equilibrium binding analysis. Highest binding capacity was obtained for MIP prepared for the template 7-hydroxycoumarin synthesized in methacrylic acid as functional monomer, chloroform as porogen and methanol/water as analyte solvent. Scanning electron microscopy analysis documented its appropriate morphology. ATR-FTIR spectra confirmed successful polymerization of MIP. Coumarin structural analogues were employed to evaluate the polymer selectivity and it was found that polymer prepared for 7-hydroxycoumarin was selective for its template molecule. Kinetic studies showed relatively fast adsorption of analytes to MIPs (1 h). Rebinding properties of MIPs were evaluated by adsorption isotherms. The calculated data fitted well with experimental data showing that Freundlich isotherm is suitable for modelling the adsorption of tested coumarins on prepared MIPs. Applicability of polymer prepared for 7-hydroxycoumarin was tested for the selective extraction of coumarins from the sample of chicory.     

Chromatographic Separation of the Enantiomers of a Series of C2-Asymmetric Bi-Naphthyl Compounds by Molecularly Imprinted Polymers

The aim of this study was to observe the chiral separation of a series of C₂-asymmetric bi-naphthyl compounds on molecularly imprinted polymers (MIPs) using 1,1′-bi-2-naphthol (BINOL) as template. MIP prepared using 4-vinylpyridine as the functional monomer showed better chiral recognition for the template than the MIPs prepared using acrylamide, 2-(diethylamino)ethylmethacrylate and 2-vinylpyridine, respectively. ¹H-NMR was used for comparison of the interactions between template and functional monomers. For chromatographic analysis the effects of mobile phase and temperature on the chiral separation were investigated. When 4-vinylpyridine was employed as the functional monomer, chiral separation of 1,1′-bi-2-naphthol and its analogues were studied. The MIP also demonstrated an ability to discriminate between enantiomers of structurally related compounds that had not been imprinted. The thermodynamic parameters of interactions between substrates and MIP in acetonitrile based mobile phase were investigated by the Van’t Hoff equation. In this study, the specific hydrogen-bonding interactions seemed to be the key factor to achieve chiral separation.     

Computer aided-molecular design and synthesis of a high selective molecularly imprinted polymer for solid-phase extraction of furosemide from human plasma

Highly selective molecularly imprinted polymers (MIPs) for solid-phase extraction and determination of furosemide in human plasma have been designed and prepared. In order to study the intermolecular interactions in the pre-polymerization mixture and to find a suitable functional monomer in MIP preparation, a computational approach was developed. It was based on the comparison of the binding energy of the complexes between the template and functional monomers. Having confirmed the results of computational method, three MIPs were synthesized with different functional monomers, i.e. acrylamide (AAM), 4-vinylpiridine (4-VP) and acrylonitrile (ACN), and then evaluated using Langmuir-Freundlich (LF) isotherm. Using the MIP prepared by AAM as functional monomer, a molecularly imprinted solid-phase extraction procedure followed by high performance liquid chromatography with ultraviolet detector (MISPE-HPLC-UV) was developed for selective extraction and determination of furosemide in human plasma. For the proposed MISPE-HPLC-UV method, the linearity between responses (peak area) and concentration was found over the range of 75-3500 ng mL⁻¹ with a linear regression coefficient (R²) of 0.997. The limit of detection (LOD) and quantification (LOQ) in plasma were 12.9 and 43.3 ng mL⁻¹, respectively.     

A comparative study of the potential of acrylic and sol-gel polymers for molecular imprinting

The successful molecular imprinting of 2-aminopyridine (2-apy) in bulk polymerisations of acrylic and sol-gel based polymers has been achieved. Both polymeric systems reveal varying degrees of affinity in rebinding the original template as well as a number of structural analogues. Rebinding was conducted in chloroform, acetonitrile and methanol in order to assess the role of hydrogen bonding in imprinting. The acrylic imprinted polymer retained approximately 50% of the template in rebinding studies in chloroform compared to 100% for the sol-gel. However, this higher affinity for the sol-gel was accompanied by a higher degree of non-specific binding. While the acrylic polymer performed poorly in acetonitrile, the sol-gel maintained a high degree of discrimination.The acrylic polymer exhibited little discrimination between imprinted and reference polymers for 3-aminopyridine (3-apy) indicating the high selectivity of the MIP polymer for 2-apy relative to 3-apy. This selectivity was reduced in acetonitrile. Selectivity of the sol-gel for 2-apy in chloroform was poor as 3-apy was retained to a similar degree. Comparable results were obtained in acetonitrile. 4-Aminopyridine (4-apy) bound strongly to all polymers in all solvents and proved very difficult to remove due to the high degree of non-specific binding for both polymeric matrices.     

Synthesis and characterization of a novel molecularly imprinted polymer for simultaneous extraction and determination of water-soluble and fat-soluble synthetic colorants in chilli products by solid phase extraction and high performance liquid chromatography

A sorbent was synthesized and investigated for molecularly imprinted solid phase extraction (MISPE). Molecularly imprinted polymers (MIP) were synthesized via precipitation polymerization procedure, where 4-vinyl pyridine (4-VP) was used as functional monomer and ethylene glycol dimethacrylate (EDMA) as cross-linking agent. The imprinting effect of the MISPE was evaluated by elution experiments. The resulting MISPE showed high extraction selectivity to water-soluble and fat-soluble synthetic colorants. The determination of multi-residue for three kinds of water-soluble and six kinds of fat-soluble synthetic colorants in chilli products was also investigated by HPLC coupled with MISPE. The mean recoveries calculated by solvent calibration curve for water-soluble and fat-soluble synthetic colorants were from 72.1% to 95.6% for chilli spice and 72.1% to 92.3% for chilli powder. The decision limit (CCα) and the detection capability (CCβ) obtained for water-soluble and fat-soluble synthetic colorants were in the range of 1.2–1.6 and 1.9–2.4 μg kg⁻¹ in chilli spice and chilli powder. The resulting MISPE was successfully used off-line for the determination of nine kinds of synthetic colorants in chilli products.     

Selective enrichment and separation of phosphotyrosine peptides by thermosensitive molecularly imprinted polymers

Novel thermosensitive molecularly imprinted polymers were successfully prepared using the epitope imprinting approach in the presence of the mimic template phenylphosphonic acid, the functional monomer vinylphosphonic acid‐Ti⁴⁺, the temperature‐sensitive monomer N‐isopropylacrylamide and the crosslinker N,N′‐methylenebisacrylamide. The ratio of the template/thermosensitive monomers/crosslinker was optimized, and when the ratio was 2:2:1, the prepared thermosensitive molecularly imprinted polymers had the highest imprinting factor. The synthetic thermosensitive molecularly imprinted polymers were characterized by Fourier transform infrared spectroscopy to reveal the combination and elution processes of the template. Then, the adsorption capacity and thermosensitivity was measured. When the temperature was 28°C, the imprinting factor was the highest. The selectivity and adsorption capacity of the thermosensitive molecularly imprinted polymers for phosphotyrosine peptides from a mixture of three tailor‐made peptides were measured by high‐performance liquid chromatography. The results showed that the thermosensitive molecularly imprinted polymers have good selectivity for phosphotyrosine peptides. Finally, the imprinted hydrogels were applied to specifically adsorb phosphotyrosine peptides from a sample mixture containing phosphotyrosine and a tryptic digest of β‐casein, which demonstrated high selectivity. After four rebinding cycles, 78.9% adsorption efficiency was still retained.