Functionalizable, Side Chain-Immolative Poly(benzyl ether)s

Abstract

Herein, we report a poly­(benzyl ether)-based self-immolative polymer (SIP) with pendant pyridine disulfide groups. Cleavage of the side-chain disulfides leads to the formation of phenolates, which initiate depolymerization from the side chain. Due to the higher density of the disulfide groups compared to that of the chain-end-capping group, which normally is responsible for initiating depolymerization of SIPs, the side chain-immolative polymer (ScIP) can be readily degraded in the solid state where the mobility of polymer chains is substantially limited. The ScIP was also further modified through the thiol–disulfide exchange reaction to prepare ScIP-g-poly­(ethylene glycol) graft polymers and organogels, which were also able to undergo complete reductive self-immolative degradation.

Thiol- and Disulfide-Based Stimulus-Responsive Soft Materials and Self-Assembling Systems

“…Xiao and coworkers [ 89 ] placed pyridyl disulfide-containing pendant groups on poly(benzyl ether) (PBE) backbones to form side chain-immolative polymers (ScIPs; Figure 23 ) which can be degraded upon exposure to reducing agents, such as DTT. These pendant groups were then reacted in a thiol-disulfide exchange reaction with either a mono-mercapto- terminated PEG (HS-PEG) or a bis-mercapto-terminated PEG (HS-PEG-HS), to produce a PEG-grafted ScIP (ScIP-g-PEG) or an extended network crosslinked by PEG groups via disulfide bonds ( Figure 24 ).…”

“… Synthesis of PBE-based ScIPs bearing pyridyl disulfide pendant groups, and their reaction with mono-or bis-mercapto-terminated PEG to form PEG-grafted ScIPs (ScIP- g -PEG) or organogel networks with PEG-disulfide crosslinks. Adapted with permission from [ 89 ]. Copyright (2019) American Chemical Society.…”

“…The graft polymer (ScIP-g-PEG), organogel, and ScIP can all be degraded by DTT. Reprinted with permission from [ 89 ]. Copyright (2019) American Chemical Society.…”

“… Proposed mechanism for the unidirectional self-immolative depolymerization of the ScIP after exposure to DTT and DBU. Data from electrospray ionization-mass spectrometry were able to identify the two molecules on the far right as the predominant products Reprinted with permission from [ 89 ]. Copyright (2019) American Chemical Society.…”

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

“…For example, Shabat and co-workers have shown that protecting groups can mask nucleophilic functionalities en route to water soluble poly(benzyl urethanes). 30 Zhang and co-workers have used post-synthetic disulfide metathesis 31 and 'click'-type reactions 32 to prepare SIP bottlebrushes and organogels. Gillies and co-workers have developed PPM strategies for preparing a range of functionalized polyglyoxylate and polyglyoxylamide SIPs via transesterification 33 and amidation reactions, 34 which significantly expand the functional scope of these polymers.…”