Post‐synthetic ‘Click’ Synthesis of RAFT Polymers with Pendant Self‐immolative Triazoles

Abstract

Self-immolative linkers offer efficient mechanisms for deprotecting 'caged' functional groups in response to specific stimuli. Herein we describe a convenient 'click' chemistry method for introducing pendant self-immolative linkers to a polymer backbone through post-polymerization modification. The intro duced triazole rings serve both to anchor the stimuli-cleavable trigger groups to the polymer backbone, while also forming a functional part of the selfimmolation cascade. We investigate the polymerization kinetics, postsynthetic modification, and self-immolation mechanism of a model polymer system, and discuss avenues for future studies on polypendant self-immolative triazoles as a modular, stimuli-responsive macromolecule platform.

Recent advances in self-immolative linkers and their applications in polymeric reporting systems

“…Subsequently, the authors have applied this methodology to 'click' their self-immolative unit to a polymer with pendant alkyne groups in order to develop a material with tuneable properties. 167 Further work, with Gillies, has seen the method used to effect post-polymerisation modification of self-immo-Scheme 31 Base mediated disassembly of self-immolative triazole 137 via 1,4-elimination reported by Blencowe et al 165 Scheme 32 Dynamic pH responsive self-immolative triazole 142 with an ethylenediamine linker permitting the use of carbamate trigger groups as described by Roberts and Stevens. 48 lative polymers (SIPs), allowing depolymerisation 168 under selective conditions e.g.…”

“…Subsequently, the authors have applied this methodology to ‘click’ their self-immolative unit to a polymer with pendant alkyne groups in order to develop a material with tuneable properties. 167 Further work, with Gillies, has seen the method used to effect post-polymerisation modification of self-immolative polymers (SIPs), allowing depolymerisation 168 under selective conditions e.g. Pd(0) catalysts or UV light (365 nm) e.g.…”

RAFT-Based Polymers for Click Reactions

“…This choice is conditioned by the high versatility of RAFT-based polymers from the standpoint of modification opportunities for both chain-end groups and by low sensitivity of the RAFT process to the chemical nature of the functional groups. The interest to the combination of RAFT polymerization and click chemistry is still growing and new publications appear almost every week [ 229 , 230 , 231 , 232 , 233 ].…”

Post-polymerization ‘click’ end-capping of polyglyoxylate self-immolative polymers

“…48 Post-synthetic 'click' activation of PEtGs P1a-b and P2a-b was initially investigated using allyl-protected cap A1, which has served as a reliable and conveniently studied model cap in previous work. 44,45 Alkyne-terminated PEtGs were treated with azide A1 (1.5-2.0 equiv.) in DMF at 50 °C under CuAAC con-Scheme 2 Overview scheme summarizing our approach for the postsynthetic 'click' activation of PEtG SIPs with self-immolative triazole (SIT) linkers.…”

“…Recently, Roberts and co-workers developed a method for preparing self-immolative triazole (SIT) linkers using the copper(I) catalyzed azide-alkyne cycloaddition (CuAAC) 'click' reaction, 44 and have demonstrated its suitability for the postsynthetic modification of RAFT polymers. 45 A key feature of this linker design is that the triazole group plays an active role in the self-immolation cascade and allows rate-tuning of the degradation kinetics through substituent effects. These features led us to hypothesize that a SIT linker, if attached to the end of a SIP, could offer a convenient way to introduce different trigger end-caps through PPM.…”