Polymers that depolymerize end-to-end upon cleavage of their backbones or end-caps, often termed “self-immolative” polymers (SIPs), have garnered significant interest in recent years. They can be distinguished from other degradable and stimuli-responsive polymers by their ability to provide amplified responses to stimuli, as a single bond cleavage event is translated into the release of many small molecules through a cascade of reactions. Here, the synthesis and properties of the major classes of SIPs including poly­(benzyl carbamate)­s, poly­(benzyl carbonate)­s, poly­(benzyl ether)­s polyphthalaldehydes, polyglyoxylates, polyglyoxylamides, and poly­(olefin sulfone)­s are presented. In addition, their advantages and limitations as well as their recent applications in areas including sensors, drug delivery, micro- and nanopatterning, transient devices and composites, coatings, antibacterial, and recyclable plastics are described. Finally, the challenges associated with the development of new SIP backbones and their translation into commercial products are discussed.

The depolymerization of coatings prepared from a 6-nitroveratryl carbonate end-capped poly(ethyl glyoxylate) (PEtG) self-immolative polymer was studied. This polymer undergoes end-to-end depolymerization following cleavage of the end-cap by UV light. Several important fundamental differences between this class of polymers and conventional degradable polymers were revealed. For example, polymer backbone cleavage and depolymerization exhibited different dependencies on pH, emphasizing the decoupling of these processes. Probing of the coating erosion mechanism illustrated an interesting combination of features from surface erosion and bulk degradation mechanisms that arise from the end-to-end depolymerization mechanism and further differentiate these polymers from convention degradable polymers. It was also demonstrated that unlike backbone cleavage, PEtG depolymerization did not exhibit a dependence on water, and that PEtG could depolymerize back to the volatile monomer ethyl glyoxylate at ambient temperature and pressure. This unusual feature was utilized to perform facile polymer reprogramming/recycling via an irradiation-trapping-repolymerization sequence as well as polymer patterning by a simple irradiation-evaporation sequence.

Amphiphilic block copolymers containing different self-immolative polyglyoxylates were synthesized and self-assembled to provide drug carriers with variable celecoxib loading capacities and release rates, as well as different in vitro toxicities.

Polyglyoxylates are a class of self-immolative polymers that depolymerize in solution and the solid state. The glyoxylic acid degradation product is a metabolite in the glyoxylate cycle and can also be processed in the liver in humans, making polyglyoxylates attractive for applications in the environment and in medicine. Although expanding the scope of available polyglyoxylates would enable new properties and applications, highly pure glyoxylate monomers are required for polymerization, and this level of purity is difficult to achieve for many potential monomers. To address this challenge, we report here the 1,5,7-triazabicyclo[4.4.0]­dec-5-ene (TBD)-catalyzed post-polymerization transesterification of poly­(ethyl glyoxylate) (PEtG) as a general method for the synthesis of directly inaccessible polyglyoxylates. Using a new end-capping strategy, PEtG compatible with the transesterification reaction was developed. n-Propanol, i-propanol, n-butanol, t-butanol, n-pentanol, n-hexanol, n-octanol, and benzyl alcohol were employed and the reactivities of these different alcohols were investigated. The resulting polyglyoxylates were characterized chemically and their thermal properties were compared. In all cases, the transesterified polyglyoxylates retained the stimuli-responsive depolymerization properties of the parent PEtG. In addition, functional polyglyoxylates based on allyl, propargyl, and furfuryl esters, which are suitable for subsequent click reactions, were prepared. The propargyl-functionalized polyglyoxylate was used to conjugate pyrene, and the resulting molecules underwent a change in fluorescence properties upon depolymerization.

Self‐immolative polymers (SIPs) undergo depolymerization in response to the cleavage of stimuli‐responsive end‐caps from their termini. Some classes of SIPs, including polycarbamates, have depolymerization rates that depend on environmental factors such as solvent and pH. In previous work, hydrophobic SIPs have been incorporated into amphiphilic block copolymers and used to prepare nanoassemblies. However, stimuli‐responsive hydrophilic blocks have not previously been incorporated. In this work, we synthesized amphiphilic copolymers composed of a hydrophobic polycarbamate SIP block and a hydrophilic poly(2‐(dimethylamino)ethyl methacrylate) (PDMAEMA) block connected by a UV light‐responsive linker end‐cap. It was hypothesized that after assembly of the block copolymers into nanoparticles, chain collapse of the PDMAEMA above its lower critical solution temperature (LCST) might change the environment of the SIP block, thereby altering its depolymerization rate. Self‐assembly of the block copolymers was performed, and the depolymerization of the resulting assemblies was studied by fluorescence spectroscopy, dynamic light scattering, and NMR spectroscopy. At 20 °C, the system exhibited a selective response to the UV light. At 65 °C, above the LCST of PDMAEMA, the systems underwent more rapid depolymerization, suggesting that the increase in rate arising from the higher temperature dominated over environmental effects arising from chain collapse. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 1868–1877