A Diels-Alder/Retro Diels-Alder Strategy to Synthesize Polymers Bearing Maleimide Side Chains TUGBA DISPINAR, RANA SANYAL, AMITAV SANYAL Department of Chemistry, Bogazici University, Bebek 34342, Istanbul, Turkey Received 13 March 2007; accepted 9 July 2007 DOI: 10.1002/pola.22299 Published online in Wiley InterScience (www.interscience.wiley.com). ABSTRACT: Polymers containing thiol-reactive maleimide groups on their side chains have been synthesized by utilization of a novel methacrylate monomer containing a masked maleimide. Diels-Alder reaction between furan and maleimide was adapted for the protection of the reactive maleimide double bond prior to polymerization. AIBN initiated free radical polymerization was utilized for synthesis of copolymers containing masked maleimide groups. No unmasking of the maleimide group was evi- dent under the polymerization conditions. The maleimide groups in the side chain of the polymers were unmasked into their reactive form by utilization of retro Diels- Alder reaction. This cycloreversion was monitored by thermo gravimetric analysis (TGA), differential scanning calorimetry (DSC), and 1 H and 13 C NMR spectroscopy. V V C 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4545–4551, 2007 Keywords: bioconjugation; biomaterials; Diels-Alder polymers; radical polymeriza- tion; functionalization of polymers; maleimide polymer INTRODUCTION Polymers with reactive side chains are macro- molecular scaffolds that have attracted wide spread attention from areas in both biology and material sciences. 1 These polymers allow devel- opment of materials that benefit from multiva- lent interactions. Such interactions between sev- eral receptor sites on the host and the ligands on the guests are abundant in biological sys- tems. Macromolecular scaffolds like polymers with strategically placed side chains can be uti- lized to mimic multivalent interactions found in biological systems. Availability of polymers with reactive side chain functionalities also provide a modular route to synthesize of a family of poly- mers with the same backbone without the neces- sity to optimize the polymerization conditions for individual monomers. The concentration of the appended side chains can be easily con- trolled by the amount of reactive functional group. In recent years, several groups have developed polymers containing functional groups that can be utilized to attach desired molecules using very efficient and clean chemical transfor- mations. 2 Perhaps the most widely used ap- proach utilizes polymers containing N-hydroxy- succinimide based activated ester groups that can be easily functionalized with amine contain- ing molecules for attachment through amide bond formation. 3 Over the past years, such mod- ular synthetic approaches have been expanded by incorporation of new monomers such as alkynes and aldehydes that can be efficiently derivatized as desired. 4 For immobilization of biomolecules, a much sought after functionalization is via thiols as cysteine residues can be engineered at specific sites of biomolecules. Cysteines can react with Correspondence to: A. Sanyal (E-mail: amitav.sanyal@ boun.edu.tr) Journal of Polymer Science: Part A: Polymer Chemistry, Vol. 45, 4545–4551 (2007) V V C 2007 Wiley Periodicals, Inc. 4545