Molecularly imprinted polymers with halogen bonding-based molecular recognition sites Toshifumi Takeuchi, a,b, * Yuji Minato, a Masayoshi Takase b and Hideyuki Shinmori a a Graduate School of Science and Technology, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan b PRESTO, Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan Received 24 September 2005; revised 18 October 2005; accepted 20 October 2005 Abstract—Molecular recognition materials bearing halogen bonding-based binding sites were synthesized by a non-covalent imprinting technique using a 2,3,5,6-tetrafluoro-4-iodostyrene (TFIS) as the functional monomer. The binding sites were generated by co-polymerizing TFIS, styrene and divinylbenzene in the presence of the template molecule (4-dimethylaminopyridine—DMAP). The imprinted polymer preferentially adsorbed aminopyridine derivatives, suggesting that halogen bonding may play a role in the selective recognition of analytes by the synthesized synthetic receptor. Ó 2005 Elsevier Ltd. All rights reserved. Halogen atoms can act as electron acceptors and inter- act with chemical species that have an ability to act as electron donors. 1 This non-covalent interaction can be strong enough to modulate the aggregation of organic molecules in solid, 2 liquid, 3 liquid crystal 4 and gas phases, 5 and the term Ôhalogen bondingÕ has been sug- gested in order to emphasize the similarity with hydro- gen bonding, which is frequently the key non-covalent interaction in chemistry, biology, and materials science. 6 It is well known that halogen molecules or alkyl and aryl halides tend to form complexes with atoms containing lone pairs. 1,6 Interactions occurring between various amino (or pyridine) derivatives and iodoperfluoro com- pounds give rise to crystalline complexes, which have been confirmed by X-ray analyses. 7 So far halogen bonding has not well-tried for use in solution, but it seems to attract wide interest as a non-covalent interac- tion. Recent articles 6,7 have shown that halogen bonding is a strong, specific and directional interaction which gives well-defined supramolecular systems. Molecular imprinting has been known as a preparation technique to yield selective molecular recognition mate- rials. 8 Molecularly imprinted polymers are synthesized by copolymerization of a functional monomer(s) and a cross-linker(s) in the presence of a template molecule to be recognized. The resulting polymers have selective binding sites complementary to the template. In non- covalent imprinting, 9 functional monomers are chosen to complement to template moleculeÕs functional groups. After the polymerization with cross-linker(s), templates are removed by washing with solvents that should weaken the interaction. The advantage of using non-covalent interaction is the ease of pre-organization of complexes between a functional monomer(s) and a template. Previously, we have reported the selective syn- thetic polymer receptors prepared by molecular imprint- ing, in which the hydrogen bonds were mainly utilized in the binding sites. 10 On the other hand, Whitcombe et al. 11 have demonstrated that the covalently imprinted polymers showed significantly uptake of 2,3,7,8-tetra- chlorodibenzodioxin (TCDD). TCDD bound to the polymer possibly by halogen bonding with aromatic chlorine atoms and p–p interactions in the binding sites, however, they did not clearly show the contribution of halogen bonding. In this letter, we attempt to construct a molecular recog- nition material by molecular imprinting using halogen bonding for DMAP (template molecule) and its relative compounds, in which halogen bonding could be a main interaction in the binding sites. Figure 1 shows an illus- tration of halogen-bonded molecular recognition site generation in this work. The used functional monomer, 2,3,5,6-tetrafluoro-4-iodostyrene (TFIS), was synthesized 0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2005.10.098 Keywords: Halogen bonding; Molecularly imprinted polymer; Mole- cular recognition. * Corresponding author. Tel./fax: +81 78 803 6158; e-mail: takeuchi@ scitec.kobe-u.ac.jp Tetrahedron Letters 46 (2005) 9025–9027 Tetrahedron Letters