Synthesis of Cleavable Amphiphilic Block Copolymers Deepak Vishnu Dharmangadan, Liying Wang, Qiuying Zhang, Mario Gauthier * Institute for Polymer Research, Department of Chemistry, University of Waterloo Conclusions References 1. Li, X.; Chen, G. Polym. Chem. 2015, 6, 1417– Chen, H.; He, S. Mol. Pharm. 2015,12, 1885– Bensaid, F. et al. Biomacromolecules 2013, 14, 1189– Ge, Z.; Liu, S. Chem. Soc. Rev. 2013, 42, 7289– Tong, R. et al. J. Chem. Soc. Rev. 2014, 43, 6982– Coady, D. J. et al. Chem. Commun. 2011, 47, 3105–3107. Amphiphilic block copolymers in solution can self-assemble into different nanostructures such as micelles, wormlike structures, and polymeric vesicles (polymersomes). 1 One important potential application of amphiphilic block copolymers is as drug carriers, 2,3 to help prevent the deactivation of therapeutic drugs such as proteins, antibodies and nucleic acids during their travel in the blood stream. 4 Depending on the types of functional groups used and the external stimuli present, different response mechanisms may come into play including pH-sensitive, thermosensitive, redox-sensitive, enzyme-sensitive, photosensitive, and so on. 5 Herewith we describe the synthesis of a novel redox-sensitive initiator for the metal-free ring opening polymerization (ROP) of lactide. A series of redox-sensitive amphiphilic block copolymers of polylactide (PLA) with polylysine (PLys) or poly(ethylene glycol) (PEG) segments were also obtained using the PLA macroinitiator. Why Lactide, Lysine and Poly(ethylene glycol)?  Lactide: Serves as monomer for the hydrophobic block. Polylactide (PLA)- based materials are highly biocompatible, biodegradable by enzymes, can hydrolyze under physiological conditions.  Lysine: Serves as monomer for the hydrophilic block. Lysine is an amino acid that the human body does not produce on its own, but it plays a key role in the makeup of body proteins.  Poly(ethylene glycol): Is highly soluble in organic solvents and, therefore, end-group modifications are relatively easy. PEG is also soluble in water and has a low intrinsic toxicity making it ideally suited for biological applications. Synthesis of Novel Redox-Sensitive Initiator Introduction  Successfully synthesized a novel redox-sensitive initiator  Synthesized polylactide with low polydispersity index by metal-free ring-opening polymerization using the novel redox-sensitive initiator  M n determined from 1 H NMR and GPC are close to the target M n  Prepared redox sensitive PLA-b-PLyz and PLA-b-PEO block copolymers with low polydispersity indices Why Metal-Free Ring Opening Polymerization?  Conventional ROP uses metal complexes with organic ligands  Drawbacks: High PDI, metal ions cannot be removed completely, high price Synthesis of Redox Sensitive Block Copolymers (PLA-b-PEG) Synthesis of Redox-Sensitive Block Copolymers (PLA-b-PLys)  Allows the synthesis of PLA with low PDI and targeted molecular weights The DBU/BA System 6 Polymer Target M n [g/mol] M n [g/mol] PDI PLA-Boc PLA-Boc PLA(2.5K)-b-PLys (1:2) PolymerTarget M n [g/mol] Measured M n [g/mol] PLA-Boc PLA-Boc PLA(2.5K)-b-PLys (1:2) MW Data from GPC MW Data from NMR