Increasing the Hydrophilicity of Cyclic Ketene Acetals Improves the Hydrolytic Degradation of Vinyl Copolymers and the Interaction of Glycopolymer Nanoparticles with Lectins

Radical ring-opening polymerization (rROP) of cyclic ketene acetals (CKAs) with traditional vinyl monomers allows the synthesis of degradable vinyl copolymers. However, since the most commonly used CKAs are hydrophobic, most degradable vinyl copolymers reported so far degrade very slowly by hydrolysis under physiological conditions (phosphate-buffered saline, pH 7.4, 37 °C), which can be detrimental for biomedical applications. Herein, to design advanced vinyl copolymers by rROP with high CKA content and enhanced degradation profiles, we reported the copolymerization of 2-methylene-1,3,6-trioxocane (MTC) as a CKA with vinyl ether (VE) or maleimide (MI) derivatives. By performing a point-by-point comparison between the MTC/VE and MTC/MI copolymerization systems, and their counterparts based on 2-methylene-1,3-dioxepane (MDO) and 5,6-benzo-2-methylene-1,3-dioxepane (BMDO), we showed negligible impact on the macromolecular characteristics and similar reactivity ratios, suggesting successful substitution of MDO and BMDO by MTC. Interestingly, owing to the hydrophilicity of MTC, the obtained copolymers exhibited a faster hydrolytic degradation under both accelerated and physiological conditions. We then prepared MTC-based glycopolymers, which were formulated into surfactant-free nanoparticles, exhibiting excellent colloidal stability up to 4 months and complete degradation under enzymatic conditions. Importantly, MTC-based glyconanoparticles also showed a similar cytocompatibility toward two healthy cell lines and a much stronger lectin affinity than MDO-based glyconanoparticles

Characterization of Functional Poly(ethylene oxide)s and Their Corresponding Polystyrene Block Copolymers by Liquid Chromatography under Critical Conditions in Organic Solvents

Separation of functional poly­(ethylene oxide) PEO and PEO block copolymers was investigated using liquid chromatography under critical conditions (LCCC) with a mixture of organic solvents as eluent. The optimum eluent is a mixture of 58.05% chloroform, 6.45% methanol, and 35.50% <i>n</i>-heptane (v/v/v) using a reverse phase (C₈) column. Unlike what was expected, the elution mechanism is governed by the interaction of a polar end-group with the column. In these conditions, poly­(ethylene oxide) (PEO) functionalized with either an acrylate or alkoxyamine moieties were separated. This allows us to investigate the efficiency of the synthesis of poly­(ethylene oxide)-<i>b</i>-polystyrene (PEO-<i>b</i>-PS) and polystyrene-<i>b</i>-poly­(ethylene oxide) <i>b</i>-polystyrene (PS-<i>b</i>-PEO-<i>b</i>-PS) block copolymers prepared via the combination of 1,2 radical intermolecular addition followed by the nitroxide-mediated polymerization NMP of styrene. Amphiphilic diblock PEO-<i>b</i>-PS and triblock PS-<i>b</i>-PEO-<i>b</i>-PS copolymers were also separated from PEO homopolymers using the same experimental conditions. We showed that the PEO block is then invisible, and the calibration curve obtained using PS homopolymer standards could be used to determine the whole molar mass of the PS block in block copolymers with PS and PEO segments, with a weak influence of the architecture

Degradable and Comb-Like PEG-Based Copolymers by Nitroxide-Mediated Radical Ring-Opening Polymerization

Three cyclic ketene acetals, 2-methylene-1,3-dioxepane (MDO), 5,6-benzo-2-methylene-1,3-dioxepane (BMDO), and 2-methylene-4-phenyl-1,3-dioxolane (MPDL), have been copolymerized with oligo­(ethylene glycol) methyl ether methacrylate and a small amount of acrylonitrile (or styrene) at 90 °C by nitroxidemediated radical ring-opening polymerization, as a convenient way to prepare degradable PEG-based copolymers for biomedical applications. MPDL was the best candidate, enabling high monomer conversions to be reached and well-defined PEG-based copolymers with adjustable amount of ester groups in the main chain to be synthesized, leading to nearly complete hydrolytic degradation (5% KOH aqueous solution, ambient temperature). The noncytotoxicity of the obtained copolymers was shown on three different cell lines (i.e., fibroblasts, endothelial cells and macrophages), representing a promising approach for the design of degradable precursors for PEGylation and bioconjugation via the NMP technique

One-Step Synthesis of Azlactone-Functionalized SG1-Based Alkoxyamine for Nitroxide-Mediated Polymerization and Bioconjugation

The one-step synthesis of azlactone-functionalized SG1-based alkoxyamine (AzSG1) for the design of functional polymers by nitroxide-mediated polymerization (NMP) is reported. At 347.7 K, its dissociation rate constant, <i>k</i>_d, was determined to be 2.72 × 10^–4 s^–1, leading to an activation energy, <i>E</i>_a, of 119.5 kJ mol^–1, which represents the lowest value ever reported for a secondary SG1-based alkoxyamine without any activation by an external stimulus. This was ascribed to enhanced stabilization of the released radical compared to other secondary alkyl radicals. The AzSG1 alkoxyamine was successfully used for the NMP for styrene, <i>n</i>-butyl acrylate, and methyl methacrylate with the addition of a small amount of acrylonitrile as a comonomer, without the need for free SG1. In all cases, first-order kinetics, good control with low dispersities (<i><i><i>Đ</i></i></i> = 1.2–1.4), and high living chain fractions (LF ∼90%) were obtained. As a proof of concept, the conjugation of azlactone-functionalized polymers to benzylamine and lysozyme was successfully demonstrated. This work may be of high interest for conjugation as the azlactone functionality is also known to react with other nucleophiles such as alcohols or thiols

Synthesis of Degradable Polyethylene and Poly(ethylene-<i>co</i>-vinyl acetate) by Radical Co- and Terpolymerization of Ethylene, ε‑Thionocaprolactone, and Vinyl Acetate

We report the synthesis of PE and poly(ethylene-co-vinyl acetate) (EVA) bearing a low content of in-chain thioester functions introduced via a co- or terpolymerization approach involving ethylene (E), vinyl acetate (VAc), and ε-thionocaprolactone (TCL). To achieve homogeneous incorporation of thioester functions along the chains resulting from the ring opening of TCL, a semibatch process with an adjusted feed of TCL was employed. Characterizations of the polymers were conducted by a combination of size exclusion chromatography (SEC) and nuclear magnetic resonance (NMR) analyses. The chemically induced degradability of the obtained polymers was assessed by SEC

Understanding the Controlled Polymerization of Methyl Methacrylate with Low Concentrations of 9‑(4-Vinylbenzyl)‑9<i>H</i>‑carbazole Comonomer by Nitroxide-Mediated Polymerization: The Pivotal Role of Reactivity Ratios

Previously, nitroxide-mediated controlled copolymerization (NMP) of methyl methacrylate (MMA) using BlocBuilder unimolecular initiator was found to require much less controlling comonomer when using 9-(4-vinylbenzyl)-9<i>H</i>-carbazole (VBK) compared to styrene (S) as a comonomer (minimum ∼1 mol % VBK versus 4.4 mol % S). Here, we explored why this was the case. Initially, the use of dimethylformamide (DMF) solvent in the copolymerization of MMA/S was studied as the MMA/VBK copolymerizations were done in DMF. The results confirmed that the increased effectiveness of VBK as a controlling comonomer was not due to the solvent or other experimental conditions. Second, the propagation rate constant <i>k</i>_P,VBK and various ⟨<i>k</i>_P⟩_MMA/VBK for MMA/VBK copolymerizations were determined using pulsed laser polymerization–size exclusion chromatography (PLP-SEC), and the dissociation rate constants <i>k</i>_d,VBK for the VBK-BlocBuilder adduct and PVBK chains were determined using electron paramagnetic resonance (EPR) spectroscopy, showing that <i>k</i>_d for VBK was very similar to S and ⟨<i>k</i>_P⟩_MMA/VBK was very similar to <i>k</i>_P,MMA. Finally, modeling of the system using PREDICI was done and illustrated that the difference in reactivity ratios between MMA/S and MMA/VBK was ultimately one of the major reasons for the increased control of VBK versus S. This study showed that propagation rate of the copolymerization and equilibrium constant for the dormant/active species are not the only parameters that govern controlled NMP, and the effect of reactivity ratios between the methacrylate and the controlling comonomer must also be considered for the controlled nitroxide-mediated copolymerization of methacrylate-rich mixtures

Enhanced Spin Capturing Polymerization of Ethylene

Enhanced spin capturing polymerization (ESCP)a recent and versatile technique in the field of controlled radical polymerizationachieves control over molecular weights and the synthesis of complex copolymer structures for a wide range of monomers. In the present work, the use of ESCP was extended to the radical polymerization of ethylene under mild conditions (low temperature and medium ethylene pressure) using a nitrone as spin trapping agent. It was demonstrated that the evolution of polyethylene (PE) molecular weight can be accurately described by classical ESCP kinetic equations. A PE bearing a midchain alkoxyamine function was thus obtained with high selectivity (90%). A more complex structure was produced from the radical polymerization of ethylene in the presence of a midchain alkoxyamine-functionalized polystyrene (PS) synthesized by ESCP in the form of ABA triblock copolymer (where A is polystyrene and B polyethylene)