Short communication Post-polymerization functionalization of epoxide-containing copolymers in trifluoroethanol for synthesis of polymer-drug conjugates Shaohua Li a , Devora Cohen-Karni a , Ethan Kallick b , Howard Edington b , Saadyah Averick a, * a Laboratory of Biomolecular Medicine, Allegheny Health Network Research Institute, Allegheny General Hospital, Pittsburgh, PA 15212, USA b Department of Surgery, Allegheny Health Network, Allegheny General Hospital, Pittsburgh, PA 15212, USA article info Article history: Received 22 March 2016 Received in revised form 7 June 2016 Accepted 8 June 2016 Available online 11 June 2016 Keywords: Poly(glycidyl methacrylate) AGET ATRP Post-polymerization functionalization abstract Post-polymerization functionalization is a critical tool in preparing functional materials. The critical aspects of post-polymerization reactions are high yields, short reaction times, simple purification, near stoichiometric amounts of reactants, and facile reaction conditions. Polymeric epoxides (i.e. poly(glycidyl methacrylate)) represent an underutilized class of functionalized polymers due to long reaction times, high temperatures, and large excess of reactants to drive the reaction to high conversion in a reasonable time frame. In this manuscript we describe the use of a novel solvent trifluoroethanol (TFE) for the ring opening of amines with poly(glycidyl methacrylate). We demonstrate that TFE gives faster reaction times and higher yields than traditional solvents used for the ring opening reaction. We utilized TFE to prepare dual functionalized polymers that could be “clicked” using strain promoted azide alkyne cycloaddition and an amine-bearing drug ring opening of the polymeric backbone. © 2016 Published by Elsevier Ltd. 1. Introduction Functionalization of reactive polymers presents a powerful tool to prepare tailor made materials. Post-polymerization modification reactions have been used to prepare a wide range of materials including drug delivery agents [1e5], imaging agents [3,6,7], bio- hybrids including DNA [8,9], RNA [10,11], and protein polymer hy- brids [12,13]. While direct polymerization of functional monomers simplifies purification strategies, the functionalization of polymers with functional moieties post-polymerization present advances in the ability to prepare libraries of functional polymers with the same backbone. Post-polymerization modification strategies also allow avoidance of monomers which are either unstable to polymeriza- tion conditions or are challenging to produce in sufficient quanti- ties as monomers (i.e. DNA/RNA). The foundation of post-polymerization strategies rests upon the use of robust chemical reactions that ideally afford high yields, short reaction times, low stoichiometric excess of reagents, and utilize facile reaction conditions with simple purification. A number of such reactive partners have been utilized including Cu-catalyzed azide alkyne cycloaddition (CuAAC) [14e19], Thiol-ene Micheal additions [20e24], Oxime-aldehyde Schiff base formation [25], and epoxide ring opening reactions [26,27]. Each method has distinct advantages and although the epoxide ring opening reactions utilize a widely available monomer (glycidyl methacrylate, GMA) readily amendable to Reversible Deactivation Radial Polymerization methods such as atom transfer radical polymerization (ATRP) and reversible addition-fragmentation chain transfer (RAFT) polymer- ization, poly(glycidyl methacrylate) had not widely been explored in the literature as a major tool for post-polymerization function- alization strategies. Recent work by Tsarevsky and coworkers [28] has discovered many new powerful methods for alcohol-epoxide ring opening reactions of poly(epoxides) prepared by RAFT exploring different catalysis to promote the ring opening reaction. In our hands we have found that typical reaction conditions for amine-promoted ring opening of polyGMA require high tempera- tures, long reaction times, and a large excess of amine to drive the reaction to satisfactory yields of functionalized polymers [27,29,30]. In this communication we describe the use of a novel solvent, tri- fluoroethanol, to promote the reaction of amines with poly(GMA). * Corresponding author. E-mail address: saverick@wpahs.org (S. Averick). Contents lists available at ScienceDirect Polymer journal homepage: www.elsevier.com/locate/polymer http://dx.doi.org/10.1016/j.polymer.2016.06.025 0032-3861/© 2016 Published by Elsevier Ltd. Polymer 99 (2016) 59e62