Dr Nathaniel Bingham

Teaching Fellow


Areas of specialism

Radical Polymerisation; Degradable Polymers; Radical Ring-Opening Polymerisation (RROP)

My teaching

My publications


Nathaniel M. Bingham, Zahra Abousalman-Rezvani, Kyle Collins and Peter J. Roth (2022). Thiocarbonyl Chemistry in Polymer Science
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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.
Nathaniel M. Bingham, Qamar un Nisa, Priyanka Gupta, Neil P. Young, Eirini Velliou, Peter J. Roth (2022). Biocompatibility and Physiological Thiolytic Degradability of Radically Made Thioester-Functional Copolymers: Opportunities for Drug Release
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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(7)-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 -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.
Nathaniel M. Bingham , Qamar un Nisa, Sophie H. L. Chua, Lea Fontugne, Matt P. Spick, Peter J. Roth (2020). Thioester-Functional Polyacrylamides: Rapid Selective Backbone Degradation Triggers Solubility Switch Based on Aqueous Lower Critical Solution Temperature/Upper Critical Solution Temperature
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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[,]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.
Matt P. Spick , Nathaniel M. Bingham, Yuman Li, Janella de Jesus, Catia Costa, Melanie J. Bailey, Peter J. Roth (2020). Fully Degradable Thioester-Functional Homo- and Alternating Copolymers Prepared through Thiocarbonyl Addition–Ring-Opening RAFT Radical Polymerization
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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[,]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 -methylmaleimide (MeMI), -phenylmaleimide (PhMI), and -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 DOT = 0.198 and PFPMI = 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 -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.
Nathaniel M. Bingham and Peter J. Roth (2018). Degradable vinyl copolymers through thiocarbonyl addition–ring-opening (TARO) polymerization
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The radical copolymerization of the thionolactone dibenzo[,]oxepane-5-thione with acrylates, acrylonitrile, and ,-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.