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Bacterial biofilm formation on medical devices is a threat to healthcare systems worldwide as bacteria within a biofilm are more resistant to standard antimicrobial therapies. Herein, we introduce a nitroxide-based antibiofilm coating strategy, which is specifically designed to prevent biofilm formation of Gram-negative pathogens such as Pseudomonas aeruginosa. Nitroxide-decorated hydroxyapatite surfaces were readily prepared in an aqueous dip-coating procedure using a nitroxide-functionalized catecholamine as a polymerizable coating agent. Additional spatial control over the polymer surface deposition on titanium was gained by applying a photolithographic coating setup. All nitroxide-coated surfaces exhibited excellent antibiofilm properties toward PA14 surface colonization as biofilm formation was completely suppressed. Importantly, the surrounding adhesive polymer matrix did not interfere with the nitroxide-characteristic antibiofilm properties. The herein introduced platform technology represents a bioinspired and versatile coating approach, offering a safe and prophylactic avenue to combat biofilm contamination on a variety of surfaces.

We pioneer an approach for the visualization of pH-controlled molecular release of a fluorescent drug from a nitroxide polymer which combined yields a profluorescent system. A methacrylate-based terpolymer, bearing water-solubilizing triethylene-glycol chains, unpaired spins in the form of nitroxide and hydrazone-bound doxorubicin was synthesized to explore the possibilities of release quantification from profluorescent assemblies. Critically, we establish the fluorescence-silencing effect of polymer-bound nitroxides on covalently attached fluorophores and the overall accessibility of such constructs. The facile approach towards a functional assembly shown here provides an easy-to-assemble construct for complex delivery architectures towards applications in theranostics.

We introduce the preparation and ring-opening polymerization of a nitroxide containing carbonate monomer. Using 1,8-diazabicyclo undec-7-ene (DBU) and a thiourea as the catalyst system, we demonstrate that the free radical moiety of the monomer has no influence on the ring-opening copolymerization with D/L-lactide in a wide range of compositions between 10% and 80% of the nitroxide monomer, which can be readily controlled by the comonomer composition in the polymerization mixture. The copolymers exhibit narrow and monomodal mass distributions with number average molar masses between 6000 g·mol −1 to 7000 g·mol −1 and low dispersities below 1.1. The free radical functionality is retained during the polymerization as demonstrated by electron spin resonance (EPR) spectroscopy. High-resolution mass spectrometry coupled to size exclusion chromatography allowed an in-depth analysis of the copolymers showing well-defined linear polymer chains with excellent endgroup fidelity. Furthermore, the molar mass of the polymers was controlled by the monomer to initiator ratio which led to copolymers of up to 19 500 g·mol −1 .

Biofilms are highly organised colonies of microorganisms, at a surface or an interface, which are extremely resistant to treatment with biocides or antimicrobials. Consequently, biofilms are the primary cause of fouling and persistent infections in both industrial and clinical settings. Thus, there is a clear need to develop coatings that are able to prevent the growth of biofilms on surfaces. Herein, we report the development of polynitroxides for use as anti-biofilm coatings. We demonstrate that we can tune the composition of the nitroxide 2,2,6,6-tetramethyl-4-piperidyl methacrylate in a copolymer with methyl methacrylate in order to control the surface concentration of nitroxides in the resulting thin films. The prepared films are able to reduce biofilm fouling by Pseudomonas aeruginosa (PAO1) at nitroxide monomer concentrations as low as 30 wt%. The nitroxide containing materials show no difference in toxicity to mammalian cells, compared to poly(methyl methacrylate), in a proliferation assay with 3T3 fibroblast cells. This is the first demonstration of surface tethered nitroxides with activity against biofilms and provides new opportunities for developing antifouling surface coatings.

We introduce the high-resolution electrospray ionization mass spectrometric (ESI MS) structural elucidation of polymerized 3,4-dihydroxy-L-phenylalanine (L-DOPA) carrying 1-methoxy-2,2,6,6-tetramethylpiperidin-4-amide groups in the side chain. Critically, our powerful ESI MS platform unambiguously revealed the structurally diverse character of this multifunctional bio-adhesive polymer system.

We pioneer a self-reporting profluorescent release system driven by the thermo-reversible dynamic covalent ligation of chromophores to a lateral polymer chain, whose fluorescence is silenced by unpaired spins of nitroxide moieties prior to release. The introduced technology platform holds significant potential for imaging substrate release events.

We introduce a mass spectrometric access route to nitroxide containing polymers via high resolution electrospray ionization mass spectrometry (HR ESI MS), a polymer class that is – due to the presence of unpaired spins – highly challenging to analyze via NMR techniques. The nitroxide content within the polymer chain structure was varied between 11.3 and 29.1 mol% in a statistical copolymer consisting of styrene-stat-4-(chloromethyl)styrene (p(S-stat-CMS), 4800 ≥ Mn/g mol−1 ≥ 11 100), where 4-carboxy-2,2,6,6-tetramethylpiperidine 1-oxyl (4-carboxy-TEMPO) units were attached by post-polymerization modification. By carefully evaluating the isotopic pattern of the nitroxide containing polymers, we demonstrate that the persistent nitroxyl radical retains its structural integrity during the soft ionization process employing spray currents up to 4.3 keV and in-source collision induced dissociation energies up to 30 eV using chloride attachment technology in negative ion mode. Interestingly, high-molecular weight gas-phase aggregates are identified with increasing amounts of nitroxide side-chain functionalization. To further exemplify the power of the introduced mass spectrometric protocol, a well-defined styrene based polymer was synthesized via atom transfer radical polymerization (ATRP, Mn = 5600 g mol−1, Đ = 1.05) containing functional groups, i.e. a terminal cyanuric acid unit and Hamilton Wedge moiety as well as a free nitroxide in the penultimate position to the Hamilton wedge. The intact persistent nitroxide radical at the chain end was unambiguously identified by its isotopic pattern in a highly defined polymer structure.

A simple modular strategy for the synthesis of profluorescent nitroxide containing polymers is described. The incorporation of an epoxide as a pendant functionality on a polymer backbone synthesized using ATRP and subsequent nucleophilic ring-opening with sodium azide gave hydroxyl and azide functionality within a 3-bond radius. Orthogonal coupling chemistry then allowed the independent attachment of fluorophore and nitroxide groups in close proximity, giving rise to a profluorescent polymer. Validation of the viability of these materials as fluorescent sensors is demonstrated through efficient fluorescence switch-on observed when the materials are exposed to a model reductant or carbon-centred radical source.

Exchange reactions between the isoindoline profluorescent nitroxide 1,1,3,3-tetramethyldibenzo[e,g]isoindolin-2-yloxyl (TMDBIO) and a TEMPO capped polystyrene were carried out. High conversions to the desired products were achieved using only stoichiometric ratios of nitroxide relative to polymer. The scope of this study was expanded by exploiting a di-nitroxide 9,10-bis(5-[1,1,3,3-tetramethylisoindolin-2-yloxy])anthracene (BTMIOA) as a connector between two polymer chains forming PS–nitroxide–PS systems.