Stimuli-Responsive Cationic Terpolymers by RAFT Polymerization: Synthesis, Characterization, and Protein Interaction Studies NICHOLAS A. A. ROSSI, 1 VAIBHAV JADHAV, 2 BENJAMIN F. L. LAI, 1 SOUVIK MAITI, 2 JAYACHANDRAN N. KIZHAKKEDATHU 1 1 Department of Pathology and Laboratory Medicine, Centre for Blood Research, Life Science Centre, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3 2 Institute of Genomics and Integrative Biology, CSIR, Delhi 110 007, India Received 20 December 2007; accepted 12 March 2008 DOI: 10.1002/pola.22743 Published online in Wiley InterScience (www.interscience.wiley.com). ABSTRACT: The controlled synthesis and characterization of a range of stimuli re- sponsive cationic terpolymers containing varying amounts of N-isopropylacrylamide (NIPAM), 3-(methylacryloylamino)propyl trimethylammonium chloride (MAPTAC), and poly(ethylene glycol)monomethyl methacrylate (PEGMA) is presented. The ter- polymers were synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization. Compositions of the terpolymers determined using 1 H NMR were in close agreement to the theoretical values determined from the monomer feed ratios. GPC-MALLS was used to analyze the molecular weight characteristics of the polymers, which were found to have low polydispersities (M w /M n 1.1–1.4). The phase transitions were studied as a function of PEGMA and NIPAM content using tempera- ture controlled 1 H NMR and turbidity measurements (UV-Vis). The relationship between thermal stability and the comonomer ratio of the polymers was measured using thermogravimetric analysis (TGA). Protein interaction studies were performed to determine the suitability of the polymers for biological applications. V V C 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4021–4029, 2008 Keywords: biocompatible; copolymerization; drug delivery systems; reversible addi- tion-fragmentation chain transfer (RAFT); stimuli-sensitive polymers INTRODUCTION The design of novel smart conjugates, drug/gene delivery vehicles, actuators, and surfaces which perform well under physiological conditions has been the subject of great interest to scientists at the interface of chemistry, biomedicine, and materials science research over recent years. 1–8 In particular, interest in the use of polymers to facilitate the delivery of drugs has stemmed from their ability to improve properties such as bioa- vailability, biocompatibility, solubility, and stabil- ity. 9 In addition, the development of synthetic materials that exhibit a responsive nature or a behavior that changes with the environmental conditions are essential to the design of smart materials for biomedical applications. 1–15 Respon- sive materials change properties such as their conformation, physical state, or binding affinity through interactions with external stimuli. This article contains Supplementary Material available via the Internet at http://www.interscience.wiley.com/jpages/ 0887-624X/suppmat. Correspondence to: J. N. Kizhakkedathu (E-mail: jay@ pathology.ubc.ca) or S. Maiti (E-mail: souvik@igib.res.in) Journal of Polymer Science: Part A: Polymer Chemistry, Vol. 46, 4021–4029 (2008) V V C 2008 Wiley Periodicals, Inc. 4021