Rational design of biomimetic molecularly imprinted materials: theoretical and computational strategies for guiding nanoscale structured polymer development

In principle, molecularly imprinted polymer science and technology provides a means for ready access to nano-structured polymeric materials of predetermined selectivity. The versatility of the technique has brought it to the attention of many working with the development of nanomaterials with biological or biomimetic properties for use as therapeutics or in medical devices. Nonetheless, the further evolution of the field necessitates the development of robust predictive tools capable of handling the complexity of molecular imprinting systems. The rapid growth in computer power and software over the past decade has opened new possibilities for simulating aspects of the complex molecular imprinting process. We present here a survey of the current status of the use of in silico-based approaches to aspects of molecular imprinting. Finally, we highlight areas where ongoing and future efforts should yield information critical to our understanding of the underlying mechanisms sufficient to permit the rational design of molecularly imprinted polymers.     

Rational design and application of molecularly imprinted sol-gel polymer for the electrochemically selective and sensitive determination of Sudan I

An electrochemical strategy on the basis of rationally designed molecularly imprinted sol-gel polymer embedded with gold nanoparticles (AuNPs) is developed for the specific and sensitive determination of Sudan I. The rationally designed sensing Sudan I imprinted sol-gel was prepared by mixing Sudan I with 3-aminopropyltriethoxysilane, tetraethoxysilane, chitosan, and AuNPs, followed by copolymerization and extraction of the template molecules. The hybrid forming membrane was characterized by SEM and FTIR-ATR, and used for the linear sweep voltammetric (LSV) determination of Sudan I in water/ethanol solutions. The LSV responses exhibited high sensitivity and selectivity, as discriminated from Sudan I analogues. Under optimal experimental conditions, LSV peak currents were linearly proportional to the concentrations of Sudan I in the range from 0.1 × 10⁻⁷ to 1.0 × 10⁻⁵ M, with a detection limit of 2.0 × 10⁻⁹ M. The strategy is generally applicable in developing sensitive, selective, and moreover, reusable electrochemical sensors for quantitative determination of electroactive species.     

Preparation of melamine molecularly imprinted polymer by computer‐aided design

Melamine was chosen as template, methacrylic acid was chosen as functional monomer, and divinylbenzene, ethylene glycol dimethacrylate, trimethylolpropane trimethylacrylate were chosen as cross‐linking agents, respectively. The WB97XD/6‐31G(d, p) method was used to calculate the geometry optimization of the different imprinting ratios, the action sites, the bonding situation, and the optimization of the cross‐linking agents. The nature of the imprinting effect was also studied by the atoms in molecules theory. The theoretical results showed that melamine interacts with methacrylic acid by hydrogen bonding, and the melamine molecularly imprinted polymers with a molar ratio of 1:6 have the most hydrogen bonds and the most stable structure. Divinylbenzene is the best cross‐linking agent for the melamine molecularly imprinted polymers. The melamine molecularly imprinted polymers were synthesized by precipitation polymerization. The results showed that the maximum adsorption capacity for molecularly imprinted polymers towards melamine is 19.84 mg/g, and the adsorption quantity of the polymers to melamine is obviously higher than that of cyromazine, cyanuric acid, and trithiocyanuric in milk. This study could provide theoretical and experimental references for the screening of the imprinting ratio and the cross‐linking agent for the given template and monomer system.     

A molecularly imprinted polymer for the determination of neopterin

A molecularly imprinted polymer (MIP) for the specific retention of neopterin has been developed. A set of 6 polymers was prepared by radical polymerization under different experimental condition using methacrylic acid as functional monomer and ethylene glycol dimethacrylate as crosslinker, with the aim to understand their influence on the efficiency of the MIP. The performance of each MIP was tested in batch experiments via their binding capacity. The MIP prepared in the presence of nickel ions in dimethylsulfoxide-acetonitrile mixture (P4) exhibited the highest binding capacity for neopterin (260 μmol per gram of polymer). A selectivity study with two other pteridines demonstrated the polymer P4 also to possess the best selectivity.

A molecularly imprinted polymer for the determination of neopterin

A molecularly imprinted polymer (MIP) for the specific retention of neopterin has been developed. A set of 6 polymers was prepared by radical polymerization under different experimental condition using methacrylic acid as functional monomer and ethylene glycol dimethacrylate as crosslinker, with the aim to understand their influence on the efficiency of the MIP. The performance of each MIP was tested in batch experiments via their binding capacity. The MIP prepared in the presence of nickel ions in dimethylsulfoxide-acetonitrile mixture (P4) exhibited the highest binding capacity for neopterin (260 μmol per gram of polymer). A selectivity study with two other pteridines demonstrated the polymer P4 also to possess the best selectivity.

A molecularly imprinted polymer for the specific retention of neopterin was developed. A set of 6 polymers was prepared under different experimental condition. The performance of each MIP was tested through their binding capacity. The MIP P4 prepared in the presence of nickel ions exhibited the highest binding capacity

     

分子印迹聚合物拆分消旋体酮洛芬

以(S) 酮洛芬为印迹分子利用分子印迹技术合成能识别(S) 酮洛芬的聚合物。聚合物作为高效液相色谱的固定相,消旋体酮洛芬在固定相能分开,同时聚合物还能将酮洛芬和布洛芬的混合物分开。     

槲皮素表面分子印迹聚合物的制备及其应用研究

以接枝双键的凹凸棒土(TM)为载体,槲皮素为模板分子,采用表面印迹技术制备对槲皮素具有特异吸附性能的分子印迹聚合物(MIP)。利用光谱法选择实验条件及对化合物表征。采用静态法研究聚合物对槲皮素的结合性能与识别性能。结果表明,该分子印迹材料对槲皮素具有特异的识别特性和优良的亲和性,提高了传统聚合物的结合率。以该印迹聚合物为固相萃取材料,结合高效液相色谱法,对白菜中的槲皮素进行分离富集,方法回收率为84.0%~90.6%,相对标准偏差低于5.6%。     

Potentiometric propranolol-selective sensor based on molecularly imprinted polymer

A novel potentiometric sensor based on molecularly imprinted polymer (MIP) for propranolol, an adrenergic-blocking drug, was designed. The influence of molecularly imprinted polymer particle content and sodium tetraphenylborate additives in polyvinylchloride membrane was shown. The electrodes show near-Nernstian responses down to 10^?4–10^?5?M propranolol concentration. The potentiometric response of MIP-based sensor for propranolol in mixed nonaqueous medium was shown at first. Sensor selectivity relative to various inorganic cations, atenolol and metoprolol, was reported. Direct potentiometry was used to determine propranolol in aqueous modeling solutions and pharmaceutical preparations with good results.     

Porous molecularly imprinted polymer membranes and polymeric particles

Porous free-standing molecularly imprinted polymer membranes were synthesised by the method of in situ polymerisation using the principle of synthesis of interpenetrating polymer networks and tested in solid-phase extraction of triazine herbicides from aqueous solutions. Atrazine-specific MIP membranes were obtained by the UV-initiated co-polymerisation of methacrylic acid, tri(ethylene glycol) dimethacrylate, and oligourethane acrylate in the presence of a template (atrazine). Addition of oligourethane acrylate provided formation of the highly cross-linked MIP in a form of a free-standing 60 μm thick flexible membrane. High water fluxes through the MIP membranes were achieved due to addition of linear polymers (polyethylene glycol M_w 20,000 and polyurethane M_w 40,000) to the initial mixture of monomers before the polymerization. As a result, typical semi-interpenetrating polymer networks (semi-IPNs) have been formed, where the cross-linked polymer was represented by the atrazine-specific molecularly imprinted polymer, while the linear one was represented by polyethylene glycol/polyurethane. Extraction of the linear polymers from the fully formed semi-IPNs resulted in formation of large pores in the membrane structure. At the same time, extraction of the template molecules lead to formation of the sites in the polymeric network, which in shape and arrangement of functional groups are complementary to atrazine. Reference polymeric membranes were prepared from the same mixture of monomers but in the absence of the template. Recognition properties of the MIP membranes were estimated in solid-phase extraction by their ability to selective re-adsorbtion of atrazine from 10⁻⁸ to 10⁻⁴ M aqueous solutions. The imprinting effect was demonstrated for both types of the MIP membranes and the influence of the type of the linear compound on their recognition properties was estimated. The recognition properties of the MIP membranes were compared to those of the MIP particles of the same composition. Morphology of the MIP membranes was investigated using the SEM microscopy. High fluxes of the developed membranes together with high affinity and adsorption capability make them an attractive alternative to MIP particles in separation processes.     

Selective recognition of ovalbumin using a molecularly imprinted polymer

Micro-contact imprinting has been used to form thin-film molecular imprints of ovalbumin (OVA) in polymers supported on glass slides. Thermocalorimetric data was used to optimise the choice of functional monomer and cross-linker to maximise selectivity and minimise non-specific recognition.A polymer comprising polyethyleneglycol 400 dimethacrylate (95 vol.%) and methacrylic acid (5 vol.%) showed both maximum recognition for OVA when made as a molecularly imprinted polymer (MIP), and minimal recognition when made as a non-imprinted, i.e. control polymer. OVA rebinding to the molecularly imprinted polymer, from a buffered 2 µM OVA solution, was 1.55 × 10^{− 11} mol cm^{− 2}, while the control polymer showed 10-fold less re-binding, i.e. 0.154 × 10^{− 11} mol cm^{− 2}.Experiments in which human serum albumin (HSA), conalbumin, ovomucoid or lysozyme, were re-bound to the polymers, either as single proteins or in competition with OVA, showed them to have low affinity for the polymer formulation used. Of the competing proteins examined, in non-competitive binding experiments, HSA showed the greatest affinity 0.45 × 10^{− 11} mol cm^{− 2} for the OVA imprinted polymer. In two protein competition experiments, i.e. with OVA and a competing protein present at equal concentrations (2 µM), OVA binding to the OVA imprinted polymer was in all cases significantly greater than that of the competitor.     

Chemosensory performance of molecularly imprinted fluorescent conjugated polymer materials

Fluorescent conjugated polymers are an attractive basis for the design of low detection limit sensing devices owing to their intrinsic signal amplification capability. A simple and universal method to rationally control or fine-tune the chemodetection selectivity of conjugated polymer materials toward a desired analytical target would further benefit their applications. In a quest of such a method we investigated a general approach to cross-linked molecularly imprinted fluorescent conjugated polymer (MICP) materials that possess an intrinsic capability for signal transduction and have potential to enhance selectivity and sensitivity of sensor devices based on conjugated polymers. To study these capabilities, we prepared an MICP material for the detection of 2,4,6-trinitrotoluene and related nitroaromatic compounds. We found the imprinting effect in this material to be based on analyte shape/size recognition being substantial and generally overcoming other competing thermodynamically determined trends. The described molecularly imprinted fluorescent conjugated polymers show remarkable air stability and photostability, high fluorescence quantum yield, and reversible analyte binding and therefore are advantageous for sensing applications due to the ability to "preprogram" their detection selectivity through a choice of an imprinted template.     

Synthesis and photoresponsive properties of a molecularly imprinted polymer

A photoresponsive molecularly imprinted polymer was prepared from a di(ureidoethylenemethacrylate)azobenzene monomer, using a methotrexate analogue as template. Photoisomerization of the 3D crosslinked polymer matrix allowed switching the substrate affinity by altering the geometry and spatial arrangement of the receptor binding sites. As a result, controlled release and uptake of the template (or analogous ligands) were obtained.     

Rational design and synthesis of water-compatible molecularly imprinted polymers for selective solid phase extraction of amiodarone

Novel water-compatible molecularly imprinted polymers (MIPs) selective for amiodarone (AD) were designed via a new methodology which relies on screening library of non-imprinted polymers (NIPs). The NIP library consisted of eighteen cross-linked co-polymers synthesized from monomers commonly used in molecular imprinting. The binding capacity of each polymer in the library was analyzed in two different solvents. Binding in water was used to assess non-specific (hydrophobic) interactions and binding in an appropriate organic solvent was used to assess specific interactions. A good correlation was found between the screening tests and modeling of monomer–template interactions performed using computational approach. Additionally, analysis of template–monomer interactions was performed using UV–vis spectroscopy. As the result, 4-vinylpyridine (4-VP) was selected as the best monomer for developing MIP for AD. The 4-VP-based polymers demonstrated imprinting factor equal 3.9. The polymers performance in SPE was evaluated using AD and its structural analogues. The recovery of AD was as high as 96% when extracted from spiked phosphate buffer (pH 4.5) solution and 82.1% from spiked serum samples. The developed MIP shown as a material with specific binding to AD, comparing to its structural analogues, 1-(2-diethylaminoethoxy)-2,6-diiodo-4-nitrobenzene and lidocaine, which shown 9.9% and 25.4% of recovery from the buffer solution, correspondingly. We believe that the screening of NIP library could be proposed as an alternative to commonly used computational and combinatorial approaches.     

Development of andrographolide molecularly imprinted polymer for solid-phase extraction

A method employing molecularly imprinted polymer (MIP) as selective sorbent for solid-phase extraction (SPE) to pretreat samples was developed. The polymers were prepared by precipitation polymerization with andrographolide as template molecule. The structure of MIP was characterized and its static adsorption capacity was measured by the Scatchard equation. In comparison with C(18)-SPE and non-imprinted polymer (NIP) SPE column, MIP-SPE column displays high selectivity and good affinity for andrographolide and dehydroandrographolide for extract of herb Andrographis paniculata (Burm.f.) Nees (APN). MIP-SPE column capacity was 11.9±0.6 μmol/g and 12.1±0.5 μmol/g for andrographolide and dehydroandrographolide, respectively and was 2-3 times higher than that of other two columns. The precision and accuracy of the method developed were satisfactory with recoveries between 96.4% and 103.8% (RSD 3.1-4.3%, n=5) and 96.0% and 104.2% (RSD 2.9-3.7%, n=5) for andrographolide and dehydroandrographolide, respectively. Various real samples were employed to confirm the feasibility of method. This developed method demonstrates the potential of molecularly imprinted solid phase extraction for rapid, selective, and effective sample pretreatment.     

分子印迹聚合物颗粒在毛细管电色谱中的应用

依据分子印迹技术(MIT)制备的分子印迹聚合物(MIP)颗粒对模板分子及其结构类似物具有特异性识别和选择性吸附作用,同时具有较大的比表面积和快速的传质动力学特性,因而被广泛用作液相色谱固定相和固相萃取材料。将MIP颗粒作为固定相应用于毛细管电色谱(CEC),结合了CEC的快速、高效和MIP的高亲和性、高选择性的特点,成为分析科学领域最具有发展前景的分离技术之一。MIP颗粒在CEC领域有几种不同的应用形式: 作为填充材料填充到毛细管柱中;作为嵌入材料嵌入到毛细管柱内部不同基质的骨架中;作为准固定相添加到CEC运行缓冲溶液中。本文综述了近几年MIP颗粒在CEC领域应用的发展,对该领域今后的发展前景进行了展望。     

硅胶表面替米考星分子印迹聚合物的制备

表面印迹接枝技术即在硅胶表面或有机聚合物载体表面[1]、毛细管表面[2]进行接枝聚合并引进分子印迹的技术[3-6]。替米考星(Tilm icosin)是一种由泰乐菌素半合成的大环内脂类畜禽专用抗生素。本文以替米考星为模板分子,以甲苯为溶剂,以甲基丙烯酸为功能单体,乙二醇二甲基丙烯酸     

Approaches to the rational design of molecularly imprinted polymers

In our experience the efficient design of molecularly imprinted polymer (MIPs) for novel templates has proved difficult. Following commonly used imprinting protocols, MIPs designed against one template show both a lack of capacity and poor specificity for rebinding either the template or structurally similar analytes. Optimisation methods that involve changing one factor at a time can be laborious.A novel approach for the optimisation of MIPs using chemometrics is described. Sulfonamides, common drug residues in foodstuffs, were used as the model analytes with a methacrylic acid/ethylene glycol dimethacrylate MIP. To avoid the inaccuracies in measurement caused by template bleed a multi-analyte competition rebind assay was developed to select suitable sulfonamides to be used as the template for the MIP, and for the rebind analyte in the chemometric optimisation study. The rebinding efficiencies were monitored by HPLC. The template sulfonamide was selected as sulfamethazine (SMZ), and the rebind analyte as sulfadimethoxine (SDIM). The template:monomer:cross-linker (T:M:X) ratio of the SMZ block MIP was then optimised using a three-level full factorial design to predict a MIP with the highest rebind capacity. On synthesis this was 38.8% for SDIM in a solid phase extraction (SPE) application agreeing with the predication. The factorial design was further utilised to predict an optimum T:M:X ratio for the production of a class specific MIP, capable of binding a range of sulfonamides simultaneously. The predicted optimum T:M:X ratios of (1:10:55) and (1:10:10) were found to be different to commonly used ratios from the MIP literature.     

Rapid preparation of molecularly imprinted polymer by frontal polymerization

Frontal polymerization was successfully applied, for the first time, to obtain molecularly imprinted polymers (MIPs). The method provides a solvent-free polymerization mode, and the reaction can be completed in 30 min. By this approach, MIPs were synthesized using a mixture of levofloxacin (template), methacrylic acid, and divinylbenzene. The effect of template concentration and the amount of comonomer on the imprinting effect of the resulting MIPs was investigated. The textural and morphological parameters of the MIP particles were also characterized by mercury intrusion porosimetry, nitrogen adsorption isotherms, and scanning electron microscopy, providing evidence concerning median pore diameter, pore volumes, and pore size distributions. The levofloxacin-imprinted polymer formed in frontal polymerization mode showed high selectivity, with an imprinting factor of 5.78. The results suggest that frontal polymerization provides an alternative means to prepare MIPs that are difficult to synthesize and may open up new perspectives in the field of MIPs.

Selectivity and recovery performance of phosphate-selective molecularly imprinted polymer

A phosphate-selective molecularly imprinted polymer was prepared using 1-allyl-2-thiourea as a functional monomer, and the binding ability and selectivity of the polymer were evaluated. The imprinted polymer showed high binding ability to and selectivity for phosphate in aqueous media. The recoverability of phosphate from the imprinted polymer was also examined, and nearly 70% of highly concentrated phosphate could be recovered.     

Tetracycline selective electrode based on molecularly imprinted polymer particles

<正>Tetracycline selective electrode using molecularly imprinted polymer particles as quasi-ionophore was constructed the first time, and its performance was carefully characterized.Due to the specific recognition of tetracycline by the particles,the selectivity coefficients for routine interferences were less than 10~(-4).Benefited from the absence of tetracycline in the sensitive membrane and the optimized composition of the inner filling solution,the limit of detection of the electrode was reduced to about 2.5×10~(-8) mol/ L.It exhibited a good electrode slope 57.6 mV/decade near the theoretical Nernstian one,with a wide linear working range from 6.0×10~(-8) to 1.0×10~(-3) mol/L.The fabricated electrode should be used in pH 2-4,response time of which was less than 200 s when the concentration of tetracycline was higher than 1.0×10~(-6) mol/L and no more than 30 min at the concentration of 1.0×10~(-8) mol/L.