ReviewTheoretical and computational strategies for rational molecularly imprinted polymer design
Introduction
The literature describing molecularly imprinted polymers (MIPs) (Alexander et al., 2006) has to a large extent been focused upon systems employing new template structures, monomers and polymerisation formats and, significantly, presenting new areas for the application of these materials. Despite the progress made in molecular imprinting science and technology (Wulff, 2002, Haupt and Mosbach, 2000, Batra and Shea, 2003, Sellergren, 2001, Komiyama et al., 2002, Yan and Ramström, 2005, Piletsky and Turner, 2006), considerably less effort has been directed towards characterising and understanding the physical mechanisms underlying MIP formation and MIP–ligand recognition (Fig. 1). For the continued development of new and improved MIPs, better insights must be obtained concerning the mechanisms underlying the molecular imprinting process in order to approach the ultimate goal of “rational MIP design”—from the molecular level events occurring in pre-polymerisation mixtures, through the polymerisation reactions, and to the factors influencing polymer–ligand recognition. For example, for the vast majority of application areas (e.g., sensor recognition elements, ligand-selective separation materials and polymers for directed synthesis), the polyclonality of MIPs and the low yields of high-fidelity sites are a challenge. In order to address this issue new strategies are required.
The earliest attempts to describe aspects of the molecular imprinting process using physical or mathematical formalism involved the use of thermodynamic models (Nicholls, 1995, Nicholls, 1998, Pande et al., 1997, Piletsky et al., 1999, Nicholls et al., 2001). The rapid increase in computing power that has taken place over the past decade, and the concurrent establishment of new and improved software, has made the use of simulations based upon mathematical descriptions realisable. Today computational techniques are being used to investigate both various aspects of the molecular imprinting process and of polymer performance. The range of computational and theoretical techniques currently in use is broad; spanning from quantum mechanical simulations to statistical treatments. Here we present both an historical perspective and the current state-of-the-art in the application of theoretical and computational methods to molecular imprinting. We provide a brief description of the principles underlying each technique to help.
Section snippets
Quantum chemical calculations
Over recent years a number of studies have been reported describing the application of ab initio and semi-empirical computational methods to the design of molecularly imprinted polymers. Briefly, such methods describe the properties of the analysed system based on an approximation of the electron distribution in the molecules studied. Numerous methods and basis sets have been developed with the aim of describing a system with high accuracy at minimal computational cost. As these methods, in
Molecular dynamics
Experimentally testing the many variables of any given imprinting protocol is an extremely labour-intensive and expensive process, if not in principle impossible. This alone provides a significant motivation for the development of computer-based solutions to assist in selecting experimental conditions. One of the most promising methods available to assist in MIP development is simulation via molecular dynamics (MD) (Leach, 2001). To briefly describe the classical method, the Newtonian laws of
Statistical treatments of MIP systems
Within the field of computational chemistry one finds an area based upon statistical methods most often entitled chemometrics (Carlsson, 1992, Eriksson et al., 2001, Esbensen, 2002). In chemometrics, mathematical and statistical methods are applied to chemical data for the selection of optimal experimental parameters and extraction of the significant information generated from multivariate data analysis. The synthesis of MIPs, as well as the rebinding of the template to the MIP, are good
Summary, conclusions and future perspectives
We have here presented the current state-of-the-art in the use of theoretical and computational techniques for describing, predicting and analysing molecular imprinting systems. Recent years have witnessed significant developments in molecularly imprinted polymer science and technology that have arisen from the use of computational techniques for the design or analysis of imprinting systems. Moreover it appears that the number of studies utilising computational approaches is increasing
Acknowledgments
The financial support provided by the Swedish Research Council (VR), the Swedish Knowledge Foundation (KKS) and the University of Kalmar is most gratefully acknowledged.
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Present address: Biomedical Diagnostics Institute, Dublin City University, Glasnevin, Dublin 9, Ireland.
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Present address: Teagasc, Ashtown Food Research Centre, Ashtown, Dublin 15, Ireland.