Theoretical and computational strategies for rational molecularly imprinted polymer design

Abstract

The further evolution of molecularly imprinted polymer science and technology necessitates the development of robust predictive tools capable of handling the complexity of molecular imprinting systems. A combination of the rapid growth in computer power over the past decade and significant software developments have 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.

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.