Computational Design of Molecularly Imprinted Polymers

Microchemical Journal, 2020

A novel protocol for use of molecularly imprinted polymer (MIP) in analysis of melamine is presented. Design of polymer for melamine has been achieved using a combination of computational techniques and laboratory trials, the former greatly reducing the duration of the latter. The compatibility and concerted effect of monomers and solvents were also investigated and discussed. Two novel open source tools were presented which are: the online polymer calculator from mipdatabase.com and the application of the Gromacs modelling suite to determine the ideal stoichiometric ratio between template and functional monomer. The MIP binding was characterised for several structural analogues at 1-100 μM concentrations. The use of DVB as cross-linking polymer and itaconic acid as functional monomer allowed synthesis of MIP with imprint factor for melamine IF=2.25. This polymer was used in HPLC for the rapid detection of melamine in spiked milk samples with an experimental run taking 7-8 minutes. This approach demonstrated the power of virtual tools in accelerated design of MIPs for practical applications.

Journal of Agricultural and Food Chemistry, 2010

A molecularly imprinted polymer able to recognize melamine in partially aqueous medium was synthesized using methacrylic acid as functional monomer and ethylene glycol dimethacrylate as cross-linking agent. The bound specificity and selectivity of the obtained material were verified by performing binding experiments with melamine and its structural analogue, 2,4,6-trimethoxy-1,3,5-triazine, respectively, using different aqueous binding media. Finally, the ability of MIP to selectively extract melamine from two real samples, a food supplement and a freeze-dried meat sample, was demonstrated.

JOURNAL OF ADVANCES IN CHEMISTRY, 2014

An easy and selective molecularly imprinted dispersive extraction method (MIDE) coupled with HPLC-DAD was developed for melamine´s analysis in commercial milk samples. The molecularly imprinted polymer (MIP) was synthetized by suspension polymerisation with melamine as template, while methacrylic acid, ethylene glycol dimethacrylate and chloroform were used as monomer, cross-linker and porogenic solvent, respectively. The analytical methodology was validated presenting a limit of detection of 0.6 mg/kg. The recovery percentage in spiked milk samples ranged from 92.9% to 102.0% with an intermediate precision of 5.0%. The analysis of real samples with MIDE revealed melamine´s presence in 20% of the cases with a maximum concentration of 9.3 ± 0.3 mg/kg, which exceeds the maximum recommended level of 2.5 mg/kg.

Talanta, 2009

In this paper, a highly selective sample cleanup procedure combining molecular imprinting and solidphase extraction (MI-SPE) was developed for the isolation of melamine in dairy products. The molecularly imprinted polymer (MIP) was prepared using melamine as the template molecule, methacrylic acid as the functional monomer and ethylene glycol dimethacrylate as the cross-linking monomer. The melamine imprinted polymer was used as selective sorbent for the solid-phase extraction of melamine from dairy products. An off-line MI-SPE method followed by high-performance liquid chromatography with diodearray detection for the detection of melamine was also established. The mean recoveries of melamine from ultra-heat treatment (UHT) milk and milk powders were 92.9-98.0% and 91.6-102.8%, respectively. Good linearity was obtained from 0.5 M to 10 M (r > 0.999) with a quantitation limit of 0.5 mol/L (0.06 ppm) which was sufficient to analyse melamine at the maximum level permitted by U.S. Food and Drug Administration (1 ppm) in dairy products. It was demonstrated that the proposed MI-SPE-HPLC method could be applied to direct determination of melamine in dairy products.

Analytica Chimica Acta, 2011

A computational model was proposed to evaluate the affinity and selectivity of 2-(3,4dimethoxyphenyl)ethylamine (homoveratrylamine) imprinted polymers. Four functional monomers: methacrylic acid, 1-vinylimidazole, 4-vinylpyridine, and allylamine were taken into account. Two dielectric constants were used for solvent simulations: a value of ε = 2.38r ij for toluene was used in the analysis of prepolymerization complexes, and a value of ε = 36r ij for methanol-water was used in the investigations of adsorption. Theoretical analysis predicted the highest affinity for the polymer synthesized from methacrylic acid. Experimental results confirmed the finding. The prepolymerization complex formed by homoveratrylamine and four methacrylic acid molecules was used to design the polymer cavity. The selectivity of the polymer was analyzed as a simulation of adsorption of six compounds in the cavity by docking procedure. Selected compounds are structurally related to the template or can be present in biological samples. The designed polymer has high selectivity towards homoveratrylamine. The proposed computational procedure could be used for successful evaluation of the imprinted polymers.

Analytica Chimica Acta, 2001

A previously described scaled-down version of the established monolith procedure, where molecularly imprinted polymers (MIPs) are prepared on the bottom surface of chromatographic vials [Anal. Chem. 71 (1999) 2092] has been here further optimised with respect to its full automation. The protocol results in savings of time and reagents compared to the monolith procedure, allowing ca. 60 polymers (∼50 mg each) to be synthesised in parallel. Both blank and imprinted polymers are then evaluated in situ by equilibrium batch rebinding tests. Each step in the synthesis and evaluation was considered with the aim of achieving an automated method with wide applicability with regards to template targets and monomer compositions. A system based on thermal initiation was considered easier to implement and applicable to a larger number of templates than one based on photo-initiation. For the purpose of choosing a suitable initiator, azo-initiators with different dissociation energies were compared. 2,2 -Azobis(2,4-dimethylvaleronitrile) (V-65) was selected as the initiator of choice based on the observed rebinding selectivity and the low temperature of use (45 • C). The time of degassing and polymerisation were also considered. With respect to the reproducibility of the automated procedure, confidence values of the mean rebinding percentage of 12 and 8 were found, respectively, for the blank and imprinted polymers when five parallel batches of ametryn blanks and imprints were submitted to rebinding tests. The small-scale protocol was then applied to the search for functional monomers for two further templates of interest: phenytoin and nifedipine. The results of the rebinding experiments on the small scale were found to be in agreement with the equilibrium rebinding evaluation of the regular scale batches. However, the equilibrium rebinding results cannot be used as a general predictor for the chromatographic selectivity of the MIPs. (F. Lanza). design. In view of the many synthetic parameters that need to be optimised in order to obtain the desired recognition properties, practical techniques for the rapid synthesis and screening of large groups of molecularly imprinted polymers (MIPs) are desirable.

ACS Omega

Simple, fast, and sensitive molecularly imprinted composite thin-filmbased electrochemical sensor developed by using in situ co-electropolymerization of aniline and acrylic acid in the presence of melamine as a template is described here. The prepolymerization complex formation was studied by using Fourier transform infrared (FTIR) spectrophotometry, while the film formation was performed and characterized by cyclic voltammetry, Fourier transform infrared (FTIR), and scanning electron microscopy (SEM). The optimization of important parameters and removal of melamine generated the binding sites in the polymer matrix, which can recognize melamine specifically. Electrochemical measurements were performed to achieve the linear range, the limit of quantification, and limit of detection of 0.1−180, 0.0573, and 0.0172 nM, respectively. The sensitivity of the sensor was attributed to the synergistic effects of amine from aniline and the carboxylic group from acrylic acid to form multiple noncovalent interactions with the template. Melamine-spiked infant formula and raw milk were analyzed by the developed sensor, and the recovery range of 95.87−105.63% with a relative standard deviation of 1.11−2.23% was obtained. The results showed that the developed sensor using the new composite polymer receptor is promising for the online monitoring of melamine in the food industries in the future.

Journal of Applied Pharmaceutical Science, 2018

The selection of functional monomers for synthesis of Molecular Imprinting Polymers (MIPs) dimethylamylamine (DMAA) compound had been conducted by non-covalent interaction identification, i.e., hydrogen bonding with DMAA, as the template. The analysis of the template complex was performed by quantum mechanical calculation using B3LYP Density Functional Theory method. The emergence of spontaneous reactions and optimum bond energy indicated the stability of formed MIPs. The results showed the functional monomers, i.e., 2-acrylamide-1-ethanosulfonic acid, itaconic acid, methacrylic acid, acrylic acid, N-(2-hydroxyethyl) acrylamide, methyl 6-O-metacryloil-α-d-glucoside, and acrylamide could be an option of MIPs synthesis consideration for DMAA with good selectivity.

Jurnal Kefarmasian Indonesia

A selective separation techniques with Molecularly Imprinted Polymer (MIP) for High-Performance Liquid Chromatography (HPLC) has been developed for the assay of Dimethylamylamine (DMAA) doping compounds. Molecular imprinted polymer (MIP) is a technique to produce a polymer having the cavity due to the disposal of the templates, in which the cavity serves to recognize the molecules of the same size, structure, chemical and physical properties. The selectivity and affinity of the templates itself will increase, while the concentration value is increasing. MIP is made by DMAA as template, acrylamide as functional monomer, ethylene glycol dimethacrylate (EGDMA) as cross linking, azobisisobutyronitrile (AIBN) as the initiator and chloroform as a porogen solvent; using bulk method. The aim of research are conduct the MIP for the DMAA compound analysis, then the formed MIP is characterized by using Fourier Transform Infra Red (FTIR) and Scanning Electron Microscopy (SEM) to find out the po...

Analytica Chimica Acta, 2009

The use of custom-made polymeric materials with high selectivities as target molecules in solid-phase extraction (SPE), known as molecularly imprinted solid-phase extraction (MISPE), is becoming an increasingly important sample preparation technique. However, the potential risk of leakage of the imprinting molecules during the desorption phase has limited application. The use of a mimicking template, called a dummy molecular imprinting polymer (DMIP), that bears the structure of a related molecule and acts as a putative imprinting molecule may provide a useful solution to this problem.