In silico screening of molecular imprinting prepolymerization systems: oseltamivir selective polymers through full-system molecular dynamics-based studies

Abstract

All-component molecular dynamics studies were used to probe a library of oseltamivir molecularly imprinted polymer prepolymerization mixtures. Polymers included one of five functional monomers (acrylamide, hydroxyethylmethacrylate, methacrylic acid, 2-(triflouromethyl)acrylic acid, 4-vinylpyridine) and one of three porogens (acetonitrile, chloroform, methanol) combined with the crosslinking agent ethylene glycol dimethacrylate and initiator 2,2'-azobis(2-methylpropionitrile). Polymers were characterized by nitrogen gas sorption measurements and SEM, and affinity studies performed using radioligand binding in various media. In agreement with the predictions made from the simulations, polymers prepared in acetonitrile using either methacrylic or trifluoromethacrylic acid demonstrated the highest affinities for oseltamivir. Further, the ensemble of interactions observed in the methanol system provided an explanation for the morphology of polymers prepared in this solvent. The materials developed here offer potential for use in solid-phase extraction or for catalysis. The results illustrate the strength of this in silico strategy as a potential prognostic tool in molecularly imprinted polymer design.

Preparation and Evaluation of Oseltamivir Molecularly Imprinted Polymer Silica Gel as Liquid Chromatography Stationary Phase

“…The kinetic adsorption is one of the most important factors in evaluating the adsorption efficiency. The effects of the adsorption time of the OSMIP@silica gel and NIP@silica gel for the OS solution were investigated by varying the time at a range from 10 to 300 min [ 10 , 22 ]. The kinetics adsorption curves are shown in Figure 3 a.…”

“…Shoravi S et al also reported a preparation method of OSMIP [ 10 ]. The full-system molecular dynamics-based studies were used to screen the molecular imprinting prepolymerization systems of OSMIP.…”

New Methods to Study the Behavior of Molecularly Imprinted Polymers in Aprotic Solvents

“…Most MIPs are solids or soft gels, and analytical techniques to directly study the structure of individual binding sites and of individual binding events in such matrices are rare [11]. Thus, information about the binding sites is obtained using mainly indirect methods, like adsorption isotherm measurements, analysis of the pre-polymerization mixture or using computer modelling [11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37].…”

“…The binding between the template and the monomer(s), which already exists in the pre-polymerization mixture, is expected to constitute an important part of the binding interactions with the solidified polymer. This has been one of the motivations for spectroscopic and computational studies of the pre-polymerization mixtures [22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37]. NMR investigation of the pre-polymerization mixture has been particularly informative concerning the stoichiometries and stabilities of pre-polymerization complexes [22,23,24,25,26].…”

“…Pre-polymerization mixtures of protein templates may be studied also by differential scanning fluorimetry (DSF) [28]. Computer modelling of the pre-polymerization mixture [25,29,30,31,32,33,34,35,36] and of the imprinting process [37] has also revealed interesting relationships regarding the interactions between all components in the pre-polymerization mixture and has contributed to the rational development of MIPs.…”