Dr Nathaniel Bingham

The radical copolymerization of the thionolactone dibenzo[c,e]oxepane-5-thione with acrylates, acrylonitrile, and N,N-dimethylacrylamide afforded copolymers containing a controllable amount of backbone thioesters which could be selectively cleaved. The process is compatible with RAFT polymerization and promising for the development of advanced degradable polymers.

The radical ring-opening polymerization (RROP) of thionolactones provides access to thioester backbone-functional copolymers but has, to date, only been demonstrated on acrylic copolymers. Herein, the thionolactone dibenzo[c,e]oxepane-5-thione (DOT) was subjected to azobisisobutyronitrile (AIBN)-initiated free-radical homopolymerization, which produced a thioester-functional homopolymer with a glass-transition temperature of 95 °C and the ability to degrade exclusively into predetermined small molecules. However, the homopolymerization was impractically slow and precluded the introduction of functionality. Conversely, the reversible addition–fragmentation chain-transfer (RAFT)-mediated copolymerization of DOT with N-methylmaleimide (MeMI), N-phenylmaleimide (PhMI), and N-2,3,4,5,6-pentafluorophenylmaleimide (PFPMI) rapidly produced well-defined copolymers with the tendency to form alternating sequences increasing in the order MeMI ≪ PhMI < PFPMI, with estimated reactivity ratios of rDOT = 0.198 and rPFPMI = 0.0078 for the latter system. Interestingly, defects in the alternating structure were more likely caused by (degradable) DOT–DOT sequences rather than (nondegradable) MI–MI sequences, which was confirmed through the paper spray mass spectrometric analysis of the products from aminolytic degradation. Upon the aminolysis of backbone thioesters, maleimide repeating units were ring-opened, forming bisamide structures. Conversely, copolymer degradation through a thiolate did not result in imide substitution but nucleophilic para-fluoro substitution on PFPMI comonomer units, indicating the ability of DOT–MI copolymers to degrade under different conditions and to form differently functional products. The RROP of thionolactones has distinct advantages over the RROP of cyclic ketene acetals and is anticipated to find use in the development of well-defined degradable polymer materials.

Radical ring-opening polymerization is a clever strategy to incorporate cleavable linkages into otherwise nondegradable vinyl polymers. However, conventional systems suffer from slow copolymerization, harsh nonselective degradation conditions, and limited application potential because the degradation products (often oligomers or polymers themselves) have properties like those of the intact species. This work presents fast selective degradation accompanied by a drastic change in a key property, aqueous solubility. Thionolactone dibenzo[c,e]oxepane-5-thione was found to copolymerize radically with a range of primary, secondary, and tertiary neutral and zwitterionic acrylamides with rapid incorporation of degradable biphenyl thiocarboxylate repeat units. Intact copolymers displayed temperature-responsive (lower critical solution temperature or upper critical solution temperature-type) aqueous solubility behavior, tunable through the molar composition and (exploiting the non-azeotropic copolymerization behavior) comonomer sequence. Various conditions led to selective and complete degradation of the backbone thioesters through hydrolysis, aminolysis, transthioesterification (including under physiological conditions), and oxidative hydrolysis, which drastically increased aqueous solubility. Polymers containing as little as 8 mol % thioester repeat units underwent a temperature-independent insoluble–soluble transition upon degradation with cysteine or potassium persulfate. Insoluble polymers were used to block syringe filters, which allowed flow of degradant solutions only, relevant to lab-on-a-chip, sensing, and embolic biomedical applications.

Being nondegradable, vinyl polymers have limited biomedical applicability. Unfortunately, backbone esters incorporated through conventional radical ring-opening methods do not undergo appreciable abiotic hydrolysis under physiologically relevant conditions. Here, PEG acrylate and di(ethylene glycol) acrylamide-based copolymers containing backbone thioesters were prepared through the radical ring-opening copolymerization of the thionolactone dibenzo[c,e]oxepin-5(7H)-thione. The thioesters degraded fully in the presence of 10 mM cysteine at pH 7.4, with the mechanism presumed to involve an irreversible S–N switch. Degradations with N-acetylcysteine and glutathione were reversible through the thiol–thioester exchange polycondensation of R–SC(═O)–polymer–SH fragments with full degradation relying on an increased thiolate/thioester ratio. Treatment with 10 mM glutathione at pH 7.2 (mimicking intracellular conditions) triggered an insoluble–soluble switch of a temperature-responsive copolymer at 37 °C and the release of encapsulated Nile Red (as a drug model) from core-degradable diblock copolymer micelles. Copolymers and their cysteinolytic degradation products were found to be noncytotoxic, making thioester backbone-functional polymers promising for drug delivery applications.

Organised by reaction type, this review highlights the unique reactivity of thiocarbonyl (C=S) groups with radicals, anions, nucleophiles, electrophiles, in pericyclic reactions, and in the presence of light. In the polymer chemistry arena, thiocarbonyl compounds have been used as monomers, polymerization catalysts, reversible and irreversible chain transfer agents, and in post-polymerization modification reactions. Past and ongoing applications are reviewed including iniferters, radical and cationic RAFT, switchable RAFT agents, cyclic RAFT agents, chain transfer, thiocarbonyl addition–ring-opening, C=S radical and anionic polymerization, acyl substitution, cationic, anionic/organo-catalytic ring-opening, Diels-Alder additions, thermolysis, and photo reactions. The review discusses the mechanisms of these reactions and highlights how the reactivity differs from oxocarbonyl analogues. Emphasis is put on the development of novel thiocarbonyl monomers which, uniquely, undergo polymerization through different mechanisms.

We report the preparation of degradable polymer networks by conventional free radical copolymerization of n-butyl acrylate with a crosslinker (1 mol %) and dibenzo[c,e]oxepane-5-thione (DOT) as a strand-cleaving comonomer. Addition of only 4 mol % of DOT imparts the synthesized networks with full degradability by aminolysis, whereas gels with less DOT (2–3 mol %) cannot be degraded. This data confirms the recently proposed reverse gel-point model for networks prepared by free radical polymerization and demonstrates the importance of considering copolymerization kinetics when designing fully degradable gels. Notably, even though DOT significantly slows down the polymerization and delays gelation, it has a minimal effect on physical properties of the networks such as shear storage modulus, equilibrium swelling ratio, glass transition temperature, or thermal stability.

Polymers with tailored architectures and degradability were prepared through thiocarbonyl addition ring-opening (TARO) atom-transfer radical polymerization (ATRP) using dibenzo[c,e]oxepin-5(7H)-thione (DOT), Cu(I)Br, and tris[2-(dimethylamino)ethyl]amine (Me6TREN) as the thionolactone, catalyst, and ligand, respectively, in combination with a selection of acrylic comonomers. Although copolymers with selectively degradable backbone thioesters and low dispersities (1.10 ≤ D̵ ≤ 1.26) were achieved using DMSO, acetonitrile, or toluene as the solvent, the Cu(I)-catalyzed dethionation of DOT to its (oxo)lactone analogue limited the achievable copolymer DOT content. Using anhydrous polymerization conditions minimized the side reaction and provided degradable copolymers with a higher (≤32 mol %) thioester content. Water-soluble molecular brushes were prepared by grafting poly(ethylene glycol) methyl ether acrylate–DOT copolymers from a pre-made multi-ATRP initiator. Due to copolymerization kinetics, the thioesters were installed close to the junctions and enabled the fast (<1 min) cleavage of the arms from the core to give water-soluble products using 10 mM oxone.

This article explores the academic and personal development outcomes from a two-week, University-wide sustainability hackathon conducted online. Data was gathered from 18 out of 23 participants through a post-hackathon questionnaire featuring 24 structured questions. These questions covered various aspects, including participants' prior work experience, motivations for participating in the hackathon, shifts in their attitudes toward sustainability, perspectives on interdisciplinary collaboration, and acquired skills. Quantitative data underwent analysis using, as appropriate, Spearman's correlation and Mann-Whitney tests, while qualitative responses were examined via thematic analysis. The results showed an improved awareness and appreciation of several personal and professional skills, encompassing ideation, product development, leadership, resilience, and teamwork. Additionally, they highlighted an increased appreciation for interdisciplinary collaboration, fostered through interaction with students from diverse academic backgrounds.

The thionolactone 3,3-dimethyl-2,3-dihydro-5H-benzo[e][1,4]dioxepine-5-thione (DBT) is shown to radically homopolymerize, copolymerize rapidly with acrylates and styrene, and, for the first time, copolymerize with methacrylates, introducing a degradable thioester backbone functionality. Surprisingly, the aminolysis of DBT homopolymers was accompanied by the intramolecular ether cleavage, leading to the formation of 2,2-dimethylthiirane and salicylamides. The rapid copolymerization with styrene was exploited to produce degradable copolymers through free-radical polymerization in a starve-fed semibatch setup. The higher reactivity of DBT compared to the current benchmark thionolactone dibenzo[c,e]oxepine-5(7H)-thione (DOT) was inconsistent with the expected electron-donating effect of the alkoxy substituent in DBT. Using single-crystal XRD structure analysis and DFT modeling, this study rationalized the higher reactivity of DBT by (i) better stabilization of the intermediate radical in DBT by means of a better overlap with the adjacent aromatic, which shifts the addition equilibrium to the right; (ii) an increased ring strain in DBT compared to DOT, which drives the ring-opening; and (iii) better reinitiating efficiency of the tertiary alkyl open-ring radical of DBT compared to the benzylic radical of DOT. These insights are expected to facilitate the development of further thionolactone monomers with tailored copolymerization behavior.