COMPUTATIONAL PREDICTION OF TEMPLATE DISCRIMINATION PROPERTIES IN MOLECULARLY IMPRINTED POLYMERS
The rapid development of molecular imprinting science and technology has driven the establishment of strategies for better understanding the mechanisms underlying imprinted polymer function and for more efficient polymer development.1 Computational strategies are finding increasing popularity in this regard, in particular the use of all-atom full-system MD modelling of pre-polymerization mixtures.2–4 In this study, we have addressed the possibility of correlating the events in the pre-polymerization mixture with polymer performance. This we have performed using a novel approach whereby a series of "cameo pictures” of template complexation are extracted from full system simulations employing multiple template molecules. These ensembles of binding sites are then used to explore the binding of the template and other ligands.
The system selected for use in this study was the imprinting of a previously reported chiral transition state analogue (TSA) for the conversion of pyridoxylamine and a-keto phenylpyruvic acid to pyridoxal and phenylalanine.5 The study included comparison of TSA binding to that of its enantiomer, and that of the substrates and products of the reaction. These studies show that this approach can provide insight into recognition site heterogeneity and, importantly, correlation to experimental data. Implications for catalysis in this polymer system shall also be discussed.
[1] Whitcombe MJ, Kirsch N, Nicholls IA (2014) Molecular imprinting science and technology: a survey of the literature for the years 2004–2011. Journal of Molecular Recognition 27: 297–401.
[2] Karlsson BCG, O’Mahony J, Karlsson JG, Bengtsson H, Eriksson LA, Nicholls IA (2009) Structure and Dynamics of Monomer−Template Complexation: An Explanation for Molecularly Imprinted Polymer Recognition Site Heterogeneity. Journal of the American Chemical Society 131: 13297–13304.
[3] Nicholls IA, Karlsson BCG, Olsson GD, Rosengren AM (2013) Computational Strategies for the Design and Study of Molecularly Imprinted Materials. Industrial and Engineering Chemistry Research 52: 13900–13909.
[4] Karim K, Breton F, Rouillon R, Piletska EV, Guerreiro A, Chianella I, Piletsky SA (2005) How to find effective functional monomers for effective molecularly imprinted polymers?. Advanced Drug Delivery Reviews 57: 1795–1808.
[5] Svenson J, Zheng N, Nicholls IA (2004) A Molecularly Imprinted Polymer-Based Synthetic Transaminase. Journal of the American Chemical Society 126: 8554–8560.
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