Molecular imprinting in ultrathin titania gel films via surface sol-gel process

Recent progresses of molecular imprinting in metal oxide matrices were summarized. Application of the surface sol-gel process to mixtures of organic carboxylic acids and titanium alkoxide provides ultrathin layers of titania gel (10-20 nm thick), in which molecule-sized cavities are kept intact upon removal of the organic templates. The imprinted cavity reflects the structural and functional features of the template molecule, and the enantioselective imprinting of dipeptide isomers is observed. Robustness and flexibility of the ultrathin titania layer is demonstrated by the formation of interconnected titania hollow structures. Possible practical applications and unsolved problems of this technique are discussed.     

Molecularly imprinted polymer grafted on polysaccharide microsphere surface by the sol-gel process for protein recognition

An interfacial organic–inorganic hybridization concept was applied to the preparation of a new spherical imprinted material for protein recognition. The functional biopolymer chitosan (CS), shaped as microsphere and high-density cross-linked, constituted of the polysaccharide core for surface imprinting. After the model template protein, bovine serum albumin, was covalently immobilized by forming imine bonds with the functional amine groups of CS, two kinds of organic siloxane (3-aminopropyltrimethoxysiloxane: APTMS, and tetraethoxysiloxane: TEOS) assembled and polymerized on the polysaccharide–protein surface via sol–gel process in aqueous solution at room temperature. After template removal, the protein-imprinted sol–gel surface exhibited a prevalent preference for the template protein in adsorption experiments, as compared with four contrastive proteins. Bioinformatics methods were also employed to investigate the imprinting process and the recognition effect. The influence of siloxane type, pH, siloxane/water ratio on template removal and recognition selectivity was assessed. Under optimized imprinting conditions, a large quantity of well-distributed pores was observed on the immobilized-template imprinted surface. The surface-imprinted adsorbent offered a fast kinetics for template re-adsorption and could be reused. Compared with the imprinted material prepared with free-template, material prepared with immobilized-template possessed higher adsorption capacity towards template protein. Easy preparation of the described imprinted material, high affinity and good reusability make this approach attractive and broadly applicable in biotechnology for down-stream processing and biosensor.     

Theoretical Investigation of Imprinted Crosslinked Silicates

Sol-gel technology excels in tailoring catalysts, electrocatalysts, sensors and biosensors, as well as membrane and other separation technologies, which require accurate control of the structure and chemical affinity of gels and xerogels. One of the most successful techniques for achieving controlled porosity is by introduction of inorganic, organic, or even biological agents during the polymerization step. Subsequent removal of the agents leaves stable vacant imprints of the template agent. However, still today template design and molecular imprinting are largely guided by experimental achievements and qualitative perceptions rather than by comprehensive theories.In this paper we review our recent theoretical efforts based on statistical mechanics models aimed at understanding and generalizing the conditions that are likely to result in successful template formation. However, the current models are still coarse-grained and consider the average size of cavities while disregarding their shape, structure, and chemical functionality.We studied three generic ways for the introduction of pore forming agents: (1) Cross-linking of functional monomers in the presence of non-covalently bonded rigid templates. (2) Polymerization of silicon species and organic monomers which are removed after gel formation using chemical treatment. (3) Polycondensation of a monomer containing a pendant group that is released during or after polymerization and cross-linking.     

Evaluation of the Polymerization and Recognition Mechanism for Phenol Imprinting SPE

In order to develop more efficient preparation technologies for imprinted polymers (MIPs), the nature of pre-polymerization and molecular recognition in MIP was investigated by molecular dynamics modeling (MD), ¹H NMR, FTIR and some indirect techniques. Phenol was used as the template for the study of mechanism through the analysis of hydrogen bonding, hydrophobic and π–π bonding interaction. The 4-vinylpyridine-based MIP had the highest selectivity to its phenol template. Hydrogen bonding was proved to be present by characterizing the pre-polymerization complex and evaluating the recognition process and the effects of rebinding solvents were also studied. It was found that a good rebinding solvent should have less affinity with both template and polymer, but good solubility. MD modeling and some indirect techniques demonstrated that 4-vinylpyridine-based MIP recognized phenol mainly through hydrophobic interactions when the rebinding medium was water, while hydrogen bonding was present in the recognition process when the rebinding solvent was n-hexane.     

Effect of the sol–gel route on the textural characteristics of silica imprinted with Rhodamine B

A series of silica xerogels that support Rhodamine B as a template were synthesized using distinct sol–gel routes, namely, acid‐catalyzed routes, a base‐catalyzed route, acid‐catalyzed with base‐catalyzed (two steps) hydrolytic routes, and a FeCl₃‐catalyzed nonhydrolytic route. The extraction methods (thermal, Soxhlet, water washing, and ultrasound) were also evaluated. The resulting xerogels were characterized through porosimetry using nitrogen adsorption/desorption. The samples were further analyzed through small‐angle X‐ray scattering, Fourier transform infrared spectroscopy, and SEM. The preparation route affected the materials’ textural properties. Extraction was optimized using acid and two‐step routes. The acid route from Rhodamine B to Rhodamine 6G generated the highest selectivity factor (2.5). The nonhydrolytic route produced the best imprinting factor. Competitive adsorption was also used, from which the approximate imprinting factor was 2. The cavity shape generated during the production of the imprinted silica dictates the adsorption behavior, not the magnitude of the surface area.     

Binding properties of 2,4,5-trichlorophenoxyacetic acid-imprinted polymers prepared with different molar ratios between template and functional monomer

Several molecularly-imprinted polymers binding the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) were prepared with a molar ratio between the functional monomer and the template molecule in the pre-polymerisation mixture set between 1+2 and 20+1. The functional monomer used was 4-vinylpyridine (4-VP), the cross-linker was ethylene dimethacrylate, and the porogenic solvent was a mixture of methanol–water 3+1 (v/v). The polymers obtained were grinded, sieved and packed in 100 mm×3.9 mm HPLC columns. The effects of the mobile phase composition were evaluated by eluting the columns with acetonitrile–water mixtures. The results obtained indicate that column capacity, selectivity factor and the imprinting effect are controlled by ion-pair and hydrophobic interactions between the analyte and the stationary phase. In the full range of ratios considered, column capacity, selectivity factor and imprinting effect are inversely proportional to the molar ratio between the template molecule and the functional monomer.     

Computational Modelling and Sustainable Synthesis of a Highly Selective Electrochemical MIP-Based Sensor for Citalopram Detection

A novel molecularly imprinted polymer (MIP) has been developed based on a simple and sustainable strategy for the selective determination of citalopram (CTL) using screen-printed carbon electrodes (SPCEs). The MIP layer was prepared by electrochemical in situ polymerization of the 3-amino-4 hydroxybenzoic acid (AHBA) functional monomer and CTL as a template molecule. To simulate the polymerization mixture and predict the most suitable ratio between the template and functional monomer, computational studies, namely molecular dynamics (MD) simulations, were carried out. During the experimental preparation process, essential parameters controlling the performance of the MIP sensor, including CTL:AHBA concentration, number of polymerization cycles, and square wave voltammetry (SWV) frequency were investigated and optimized. The electrochemical characteristics of the prepared MIP sensor were evaluated by both cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) techniques. Based on the optimal conditions, a linear electrochemical response of the sensor was obtained by SWV measurements from 0.1 to 1.25 µmol L⁻¹ with a limit of detection (LOD) of 0.162 µmol L⁻¹ (S/N = 3). Moreover, the MIP sensor revealed excellent CTL selectivity against very close analogues, as well as high imprinting factor of 22. Its applicability in spiked river water samples demonstrated its potential for adequate monitoring of CTL. This sensor offers a facile strategy to achieve portability while expressing a willingness to care for the environment.     

Evaluation of a novel silica-supported sol–gel sorbent prepared by a surface molecular imprinting technique for the selective separation of estazolam from human plasma

A molecular imprinting polymer (MIP) based on surface modification of silica gel was prepared via the sol–gel process with 3-aminopropyltriethoxysilane and phenyltrimethoxysilane as functional monomers, and estazolam as the template. The imprinted silica sorbent was characterized by Fourier Transform Infrared Spectroscopy, surface elemental analysis, and scanning electron microscopy (SEM). An MIP of agglomerated nano-particles with multi-pores was grafted onto the surface of the silica gel after hydrolytic condensation of the siloxane. The imprinted silica sorbent was used for solid phase extraction (SPE). Using water as loading solvent, the extraction efficiency for estazolam was higher compared to the use of an organic solvent. The imprinted silica sorbent was selective not only for the template, but also for the analogue. Compared to C₁₈-SPE and liquid–liquid extraction, the MIP-SPE was the most feasible technique for extraction of estazolam from human plasma; up to 98.7?±?1.2% recovery was achieved.     

胆酸印迹聚合物的制备及在含水介质中的结合性能

为了在含水介质中进行有效印迹,本研究中以双甲基丙烯酰-β-环糊精（BMA-β-CD）和2-(二乙基胺基)乙基甲基丙烯酸酯(DEAEM)为功能单体制备了胆酸印迹聚合物MIP1,并用平衡结合实验研究了MIP1在含水介质中对模板分子的识别能力。结果表明,MIP1比单独以BMA-β-CD或DEAEM为功能单体制备的印迹聚合物MIP2和MIP3,显示出对模板分子更好的选择性结合能力。MIP1的特异性吸附量ΔCP为38.81μmol/g,印迹因子IF为2.46。研究表明,在含水介质中,利用模板分子与功能单体之间的疏水作用和离子作用是提高印迹聚合物分子识别能力的关键。研究还表明,在识别过程中,疏水作用在驱动分子进入印迹孔穴时起重要作用。     

Molecular dynamics simulations of triflic acid and triflate ion/water mixtures: a proton conducting electrolytic component in fuel cells

Triflic acid is a functional group of perflourosulfonated polymer electrolyte membranes where the sulfonate group is responsible for proton conduction. However, even at extremely low hydration, triflic acid exists as a triflate ion. In this work, we have developed a force-field for triflic acid and triflate ion by deriving force-field parameters using ab initio calculations and incorporated these parameters with the Optimized Potentials for Liquid Simulations - All Atom (OPLS-AA) force-field. We have employed classical molecular dynamics (MD) simulations with the developed force field to characterize structural and dynamical properties of triflic acid (270-450 K) and triflate ion/water mixtures (300 K). The radial distribution functions (RDFs) show the hydrophobic nature of CF(3) group and presence of strong hydrogen bonding in triflic acid and temperature has an insignificant effect. Results from our MD simulations show that the diffusion of triflic acid increases with temperature. The RDFs from triflate ion/water mixtures shows that increasing hydration causes water molecules to orient around the SO(3)(-) group of triflate ions, solvate the hydronium ions, and other water molecules. The diffusion of triflate ions, hydronium ion, and water molecules shows an increase with hydration. At λ = 1, the diffusion of triflate ion is 30 times lower than the diffusion of triflic acid due to the formation of stable triflate ion-hydronium ion complex. With increasing hydration, water molecules break the stability of triflate ion-hydronium ion complex leading to enhanced diffusion. The RDFs and diffusion coefficients of triflate ions, hydronium ions and water molecules resemble qualitatively the previous findings using per-fluorosulfonated membranes.     

萘普生分子印迹拆分及亲和吸附平衡常数的测定

分子印迹 (Molecular imprinting)是一种新的、很有发展潜力的分离技术 [1～ 3 ] .该技术已成功地用于氨基酸、糖类及其衍生物和药物的手性分离 .萘普生是一种重要的非甾体消炎、解热和镇痛药 ,为了减少给药量和对人体产生的毒副作用 ,必须对其进行手性拆分 . Mosbach等 [4 ] 曾以 4-乙烯基吡啶为功能单体 ,利用分子印迹对外消旋萘普生进行了手性拆分 ,但 4-乙烯基吡啶使用前需经过减压蒸馏 ,使用不便 . Haginaka等 [5～ 7] 也采用 4-乙烯基吡啶为功能单体 ,以 (S) -萘普生为模板制得了均一粒径的分子印迹介质 .尽管分子印迹分离技术发展…     

Development of a model for the rational design of molecular imprinted polymer: Computational approach for combined molecular dynamics/quantum mechanics calculations

A new rational approach for the preparation of molecularly imprinted polymer (MIP) based on the combination of molecular dynamics (MD) simulations and quantum mechanics (QM) calculations is described in this work. Before performing molecular modeling, a virtual library of functional monomers was created containing forty frequently used monomers. The MD simulations were first conducted to screen the top three monomers from virtual library in each porogen-acetonitrile, chloroform and carbon tetrachloride. QM simulations were then performed with an aim to select the optimum monomer and progen solvent in which the QM simulations were carried out; the monomers giving the highest binding energies were chosen as the candidate to prepare MIP in its corresponding solvent. The acetochlor, a widely used herbicide, was chosen as the target analyte. According to the theoretical calculation results, the MIP with acetochlor as template was prepared by emulsion polymerization method using N,N-methylene bisacrylamide (MBAAM) as functional monomer and divinylbenzene (DVB) as cross-linker in chloroform. The synthesized MIP was then tested by equilibrium-adsorption method, and the MIP demonstrated high removal efficiency to the acetochlor. Mulliken charge distribution and ¹H NMR spectroscopy of the synthesized MIP provided insight on the nature of recognition during the imprinting process probing the governing interactions for selective binding site formation at a molecular level. We think the computer simulation method first proposed in this paper is a novel and reliable method for the design and synthesis of MIP.     

N,N-dimethylformamide-induced phase separation of hexafluoroisopropanol-water mixtures

We found that addition of N,N-dimethylformamide (DMF) induces phase separation of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP)-water mixtures. The phase diagram of a DMF-HFIP-water ternary system at 298 K showed that phase separation occurs in a closed-loop area in the water-rich mole fraction range of x(H(2)O) > ～0.4. To clarify the mechanism of DMF-induced phase separation of DMF-HFIP-water mixtures at the molecular level, small-angle neutron scattering (SANS) and (1)H and (13)C NMR measurements were conducted on the mixtures with varying DMF concentrations along a volume ratio of HFIP to water of 1?:?1 (x(S)(HFIP) = 0.147). Additionally, the solvation structure of DMF in water and HFIP-water mixtures was elucidated by molecular dynamics (MD) simulations. The SANS results revealed that the inherent heterogeneity of HFIP-water mixtures is increased with increasing DMF concentration toward the lower phase separation concentration, but decreased when the DMF concentration further increased beyond the upper phase separation one. (1)H and (13)C NMR measurements and MD simulations suggested that preferential solvation of the hydrophobic moiety of DMF by HFIP is the main driver of the phase behaviour of the DMF-HFIP-water system.     

Hydroxamate类抑制剂与MMP-2的分子对接研究

通过分子动力学模拟研究了MMP-2和hydroxamate抑制剂之间的作用模式。在分子动力学模拟中,对于催化区的锌离子和其共价结合的配体(包括抑制剂和组氨酸)采用了键合的模型。从模拟的结果可以看到,R^1取代基和MMP-2的S1疏水口袋中的部分残基能形成很好的几何匹配,从而可以产生很强的范德华和疏水相互作用。模拟结果也表明,两个抑制剂和MMP-2之间分别能形成5个和8个氢键,抑制剂B比A活性更高的原因就是能够形成更加有利氢键作用模式。在整个模拟过程中,催化锌都能保持好的五配位形式,配位键的长度也处于稳定的状态,预测得到的MMP-2和其抑制剂的相互作用模式对于全新抑制剂的设计提供了非常重要的结构信息。     

An Artificial Estrogen Receptor through Combinatorial Imprinting

Polymeric sorbents targeting endocrine‐disrupting estrogen active compounds (EAC) were prepared by terpolymer imprinting using 17β‐estradiol (E2) as template. From a group of eight functional monomers representing Brønsted acids, bases, hydrogen‐bond donors and acceptors, as well as π‐interacting monomers, a terpolymer library that comprises all possible binary combinations of the functional monomers was prepared. Binding tests revealed that imprinted polymers exhibit a markedly higher affinity for E2 compared to nonimprinted polymers (NIPs) or polymers prepared by using single functional monomers. A combination of methacrylic acid (MAA) and p‐vinylbenzoic acid offered a particularly promising lead polymer, displaying an imprinting factor of 17 versus 2.4 for a benchmark polymer prepared by using only MAA as functional monomer. The saturation capacities ascribed to imprinted sites were four to five times higher for this polymer compared to previously reported imprinted polymers. NMR titrations and molecular dynamics simulations corroborated these results, indicating an orthogonal preference of the two functional monomers with respect to the E2 3‐OH and 17‐OH groups. The optimized polymer exhibited a retentivity for EACs that correlates with their inhibitory effect on the natural receptor. By using the optimized molecularly imprinted polymers (MIPs) in a model water‐purification system, they were capable of completely removing ppb levels of a small group of EACs from water. This is in contrast to the performance of nonimprinted polymers and well‐established sorbents for water purification (e.g., active carbon), which still contained detectable amounts of the compounds after treatment.     

计算机分子模拟在分子印迹技术中的应用

传统的分子印迹技术对模板分子、功能单体、交联剂、致孔剂等的筛选往往依靠经验,常通过反复实验对合成条件进行优化,存在实验周期长、耗材量大等问题。计算机分子模拟技术的应用在实验过程中起到可预见性指导作用,可以实现精准识别位点的裁制、识别驱动力的设计,通过结合能等物化特征参数计算优化识别体系的稳定性,从而合理选择模板分子、功能单体、交联剂、致孔剂,优化聚合条件,以提高聚合物识别特异性和亲和力,缩短实验周期,更符合绿色化学的理念。本文简单介绍了计算机分子模拟技术,重点对其在分子印迹技术中的指导作用进行了综述,并对其在分子印迹技术中的应用进行了展望。     

Molecular recognition properties of salicylic acid-imprinted polymers

Summary Two molecularly imprinted polymers (MIP) have been prepared using the acidic drug salicylic acid, which can form intramolecular hydrogen bond, as the template and acrylamide or 4-vinylpyridine as the functional monomer. HPLC was used to evaluate the binding performance of the MIP for the template and for several analogues. The results showed that the MIP (P₂) prepared using acrylamide as the functional monomer had no molecular imprinting effect whereas that (P₁) prepared using 4-vinylpyridine as the functional monomer had a significant molecular imprinting effect. The reason the molecular imprinting effect was different for the two MIP was elucidated and the molecular recognition properties of P₁ were studied in detail. It was confirmed that electrostatic interaction played an important role in the molecular recognition of P₁. Scatchard analysis showed that two types of binding site with distinctly different affinity were formed in P₁. Their dissociation constants were estimated to be 7.6×10⁻⁵ mol L⁻¹ and 3.2×10⁻³ mol L⁻¹, respectively. Because P₁ has high affinity and selectivity for salicylic acid not only in organic systems but also in water-containing systems, it gives P₁ the potential for use in the enrichment, separation, and detection of salicylic acid in biological fluids.     

On-column concentration of bisphenol A with one-step removal of humic acids in water

An efficient extraction method for bisphenol A from environmental water including contaminants was developed using surface selective localization of functional group, on a polymeric separation device. The polymer utilized in this study was prepared through a kind of molecular imprinting technique, namely fragment imprinting effect utilizing a pseudo-template molecule (p-tert.-butylphenol) instead of bisphenol A. The concentration of bisphenol A onto the polymer device prepared, up to 1000 times concentration from environmental water including contaminants (humic acids), was achieved very easily with interesting exclusion effect for humic acids. The results obtained in this study suggest that molecular imprinting with the pseudo-template molecule is quite an effective way for selective concentration of the diluted target molecule from other contaminants including similar functional group with the target molecule.     

Molecular dynamics simulation study of the structural characteristics of water molecules confined in functionalized carbon nanotubes

Molecular dynamics (MD) simulations were performed to study the structural properties of water molecules confined in functionalized carbon nanotubes (CNTs). Four CNTs, two armchair-type (6, 6), (7, 7) and two zigzag-type (10, 0), (12, 0) CNTs, representing different helicities and different diameters, were chosen and functionalized at their open ends by the hydrophilic -COOH and the hydrophobic -CH3 groups. The structural properties of water molecules inside the functionalized CNTs, including the orientation distributions of dipole moment and O-H bonds, the length of the single-file water chain, and the average number of hydrogen bonds, were analyzed during a process of simulations. MD simulation results in this work showed that the -CH3 functional groups exert little special effects on the structural properties of water molecules. It is mainly due to the relatively small size of the -CH3 group and its hydrophobic nature, which is consistent with hydrophobic CNTs. For CNTs functionalized by -COOH groups, the configurations of -COOH groups, incurvature or excurvature, determine whether water molecules can enter the CNTs. The incurvature or excurvature configurations of -COOH groups are the results of synergy effects of the CNTs' helicity and diameter and control the flow direction of water molecules in CNTs.     

Preparation of molecularly imprinted polymer microspheres via atom transfer radical precipitation polymerization

The first combined use of atom transfer radical polymerization (ATRP) and precipitation polymerization in the molecular imprinting field is described. The utilized polymerization technique, namely atom transfer radical precipitation polymerization (ATRPP), provides MIP microspheres with obvious molecular imprinting effects towards the template, fast template binding kinetics and an appreciable selectivity over structurally related compounds. The living chain propagation mechanism in ATRPP results in MIP spherical particles with diameters (number‐average diameter D_n ≈ 3 μm) much larger than those prepared via traditional radical precipitation polymerization (TRPP). In addition, the MIP microspheres prepared via ATRPP have also proven to show significantly higher high‐affinity binding site densities on their surfaces than the MIP generated via TRPP, while the binding association constants K_a and apparent maximum numbers N_max of the high‐affinity sites as well as the specific template bindings are almost the same in the two cases. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 3257–3270, 2009