Fundamental studies of molecularly imprinted polymer¹ (MIP) systems are necessary in order to facilitate the development of the field in general, in particular through the development of rational MIP design strategies.² Recent efforts using molecular dynamics studies of all-component molecular imprinting systems have demonstrated the unique insights that can be obtained regarding the massive diversity of interactions present in a given system.³

One of the most widely used templates in molecular imprinting is the beta-blocker propranolol.^4-8 Its use in fundamental studies and for providing proof-of-principle cases has been motivated by a number of factors including its clinical relevance, its inherent chirality, and availability in enantiomerically pure and radio-labelled forms. Significant efforts have been made to map the molecular basis for propranolol-MIP ligand recognition, though never through the simultaneous study of all components present during polymerization.

Here we present the first all component MD study of this system which has provided unique insights concerning, in particular the role of cross-linking agent on template complexation. Through correlations with recognition data, consequences for MIP design are proposed.

(1)      Alexander, C.; Andersson, H.S.; Andersson, L.I.; Ansell, R.J.; Kirsch, N.; Nicholls, I.A.; O'Mahony, J.; Whitcombe, M.J. J. Mol. Recognit. 2006, 19, 106-180.

(2)      Nicholls, I. A.; Andersson, H. S.; Charlton, C.; Henschel, H.; Karlsson, B. C. G.; Karlsson, J. G.; O´Mahony, J.; Rosengren, A. M.; Rosengren, K. J.; Wikman, S. Biosens. Bioelectron. 2009, 25, 543-552.

(3)      Karlsson, B. C. G.; O´Mahony, J.; Karlsson, J. G.; Bengtsson, H.; Eriksson, L. A.; Nicholls, I. A. J. Am. Chem. Soc., 2009, 131, 13297-13304.

(4)      Andersson, L.I. Anal. Chem. 1996, 68, 111-117.

(5)      Schweitz, L.; Andersson, L.I.; Nilsson, S. Anal. Chem. 1997, 69, 1179-1183.

(6)      Haupt, K.; Noworyta, K.; Kutner, W. Anal. Commun. 1999, 36, 391-393.

(7)      Philip, J.Y.N.; Buchweishaija, J.; Mkayula, L.L.; Ye, L. J. Agric Food Sci. 2007, 55, 8870-8876.

(8)      Nguyen, T.H.; Ansell, R.J. Org. Biomol. Chem. 2009, 7, 1211-1220.