2-Cyanopropan-2-yl versus 1-Cyanocyclohex-1-yl Leaving Group: Comparing Reactivities of Symmetrical Trithiocarbonates in RAFT Polymerization.

This study introduces bis(1-cyanocyclohex-1-yl)trithiocarbonate (TTC-bCCH) as a novel trithiocarbonate chain transfer agent and compares its reactivity with the previously described bis(2-cyanopropan-2-yl)trithiocarbonate (TTC-bCP) for the reversible addition-fragmentation chain transfer (RAFT) polymerization of styrene (St), n-butyl acrylate (nBA), and methyl methacrylate (MMA). Significant findings include the effective control of Mn and low dispersities from the onset of polymerization of St and nBA showing swift addition-fragmentation kinetics, leading to similar behaviors between the two RAFT agents. In contrast, a fourfold decrease of the chain transfer constant to MMA is established for TTC-bCCH over TTC-bCP. This trend is confirmed through density functional theory (DFT) calculations. Finally, the study compares thermoplastic elastomer properties of all-(meth)acrylic ABA block copolymers produced with both RAFT agents. The impact of dispersity of PMMA blocks on thermomechanical properties evaluated via rheological analysis reveals a more pronounced temperature dependence of the storage modulus (G') for the triblock copolymer synthesized with TTC-bCCH, indicating potential alteration of the phase separation.

α-Amido Trifluoromethyl Xanthates: A New Class of RAFT/MADIX Agents.

Xanthates have long been described as poor RAFT/MADIX agents for styrene polymerization. Through the determination of chain transfer constants to xanthates, this work demonstrated beneficial capto-dative substituent effects for the leaving group of a new series of α-amido trifluoromethyl xanthates, with the best effect observed with trifluoroacetyl group. The previously observed Z-group activation with a O-trifluoroethyl group compared to the O-ethyl counterpart was quantitatively established with Cex = 2.7 (3-4 fold increase) using the SEC peak resolution method. This study further confirmed the advantageous incorporation of trifluoromethyl substituents to activate xanthates in radical chain transfer processes and contributed to identify the most reactive xanthate reported to date for RAFT/MADIX polymerization of styrene.

Membrane-Active Thermoresponsive Block Copolymers Containing a Diacylglycerol-Based Segment: RAFT Synthesis, Doxorubicin Encapsulation, and Evaluation of Cytotoxicity against Breast Cancer Cells.

Herein, we report the formation of drug delivery systems from original thermoresponsive block copolymers containing lipid-based segments. Two acrylate monomers derived from palmitic- or oleic-acid-based diacylglycerols (DAGs) were synthesized and polymerized by the reversible addition-fragmentation chain transfer (RAFT) method. Well-defined DAG-based polymers with targeted molar masses and narrow molar mass distributions were next used as macro-chain transfer agents (macro-CTAs) for the polymerization of N-isopropylacrylamide (NIPAAm) or N-vinylcaprolactam (NVCL). The obtained amphiphilic block copolymers were formed into polymeric nanoparticles (PNPs) with and without encapsulated doxorubicin and characterized. Their biological assessment indicated appropriate cytocompatibility with the representatives of normal cells. Furthermore, compared to the free drug, increased cytotoxicity and apoptosis or necrosis induction in breast cancer cells was documented, including a highly aggressive and invasive triple-negative MDA-MB-231 cell line.

Tailor-Made Poly(vinylamine) via Purple LED-Activated RAFT Polymerization of N-vinylformamide.

Photo-iniferter reversible addition-fragmentation chain transfer (PI-RAFT) polymerization of N-vinylformamide (NVF) is demonstrated by using purple light. PNVFs with predetermined molar masses and narrow molar mass distributions are obtained. High RAFT chain-end fidelity is confirmed by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) and electrospray-ionization time-of-flight mass spectrometry (ESI-TOF-MS), and chain extension experiment. To demonstrate the potential of this approach, an original poly(N-vinylpyrrolidone)-b-poly(N-vinylformamide) (PVP-b-PNVF) diblock copolymer is synthesized and characterized by aqueous size-exclusion chromatography (SEC), asymmetric flow field-flow fractionation (A4F), and 1 H diffusion-ordered spectroscopy nuclear magnetic resonance (1 H DOSY NMR). Finally, selective hydrolysis of PNVF block to corresponding pH-responsive poly(N-vinylpyrrolidone)-b-poly(N-vinylformamide) (PVP-b-PVAm) is performed.

Azo-Derived Symmetrical Trithiocarbonate for Unprecedented RAFT Control.

Bis(2-cyanopropan-2-yl)trithiocarbonate (TTC-bCP) is a new symmetrical trithiocarbonate with the best leaving group ever reported for reversible addition-fragmentation chain transfer (RAFT) polymerization. We propose an elegant route to obtain TTC-bCP starting from 2,2'-azobis(2-methylpropionitrile) (AIBN) as a donor of the 2-cyanopropan-2-yl group. TTC-bCP allowed the preparation of a high-molar-mass (Mn ≈ 135 kg mol-1) methyl methacrylate-n-butyl acrylate-methyl methacrylate triblock copolymer with unprecedented control (D̵ = 1.04) in reversible-deactivation radical polymerization. Rheology measurements of this triblock copolymer showed a typical thermoplastic elastomer behavior with a steady rubbery plateau up to 120 °C.

Effect of Hydrophilic Monomer Distribution on Self-Assembly of a pH-Responsive Copolymer: Spheres, Worms and Vesicles from a Single Copolymer Composition.

A series of copolymers containing 50 mol % acrylic acid (AA) and 50 mol % butyl acrylate (BA) but with differing composition profiles ranging from an AA-BA diblock copolymer to a linear gradient poly(AA-grad-BA) copolymer were synthesized and their pH-responsive self-assembly behavior was investigated. While assemblies of the AA-BA diblock copolymer were kinetically frozen, the gradient-like compositions underwent reversible changes in size and morphology in response to changes in pH. In particular, a diblock copolymer consisting of two random copolymer segments of equal length (16 mol % and 84 mol % AA content, respectively) formed spherical micelles at pH >5, a mix of spherical and wormlike micelles at pH 5 and vesicles at pH 4. These assemblies were characterized by dynamic light scattering, cryo-transmission electron microscopy and small angle neutron scattering.

Synthesis of S-Alkyl Phosphinocarbodithioates with Switch between P(III) and P(V) Derivatives.

Simple and effective synthetic pathways are described to prepare compounds R2P(X)C(S)SCH(Me)Ph with the P atom either in the oxidation state V [R/X = t-Bu/O (6), Ph/S, (7), t-Bu/S (8), t-Bu/Se (9)] or III [R/X = Ph/BH3 (4), t-Bu/BH3 (5), t-Bu/lone pair (10)]. Compound 9 is the first example of carbodithioate ester with a P = Se group, and for the first time, a phosphinocarboditioate with a free phosphine function (compound 10) is described. Stabilization of the latter crucially depends on the steric protection by the t-Bu groups since an analogous derivative with R = Ph is observable but too unstable for isolation. Compound 10 can be reversibly protonated to yield the [t-Bu2PHC(S)SCH(Me)Ph]+ cation (10-H+), which was isolated as a BF4- salt. A few interconversion processes resulting in the facile addition/removal or exchange of the X group in this family of compounds are also described. The oxidation state of the phosphorus atom and the nature of an electron-withdrawing group have a significant impact on the spectral properties.

Structure-Property Relationships in CO2-philic (Co)polymers: Phase Behavior, Self-Assembly, and Stabilization of Water/CO2 Emulsions.

This Review provides comprehensive guidelines for the design of CO2-philic copolymers through an exhaustive and precise coverage of factors governing the solubility of different classes of polymers. Starting from computational calculations describing the interactions of CO2 with various functionalities, we describe the phase behavior in sc-CO2 of the main families of polymers reported in literature. The self-assembly of amphiphilic copolymers of controlled architecture in supercritical carbon dioxide and their use as stabilizers for water/carbon dioxide emulsions then are covered. The relationships between the structure of such materials and their behavior in solutions and at interfaces are systematically underlined throughout these sections.

Asymmetric Copolymers: Synthesis, Properties, and Applications of Gradient and Other Partially Segregated Copolymers.

Asymmetric copolymers are a class of materials with intriguing properties. They can be defined by a distribution of monomers within the polymer chain that is neither strictly segregated, as in the case of block copolymers, nor evenly distributed throughout each chain, as in the case of statistical copolymers. This definition includes gradient copolymers as well as block copolymers that contain segments of statistical copolymer. In this review, different methods to synthesize asymmetric copolymers are first discussed. The properties of asymmetric copolymers are investigated in comparison to those of block and random counterparts of similar composition. Finally, some examples of applications of asymmetric copolymers, both academic and industrial, are demonstrated. The aim of this review is to provide a perspective on the design and synthesis of asymmetric copolymers with useful applications.

Alkyl Triarylstannanecarbodithioates: Synthesis, Crystal Structures, and Efficiency in RAFT Polymerization.

Eight alkyl triarylstannanecarbodithioates were synthesized starting from the corresponding triarylstannyl chlorides. They were fully characterized by IR and 1 H, 13 C, and 119 Sn NMR spectroscopy and mass spectrometry. Their solid-state structures and geometric parameters were determined and compared to those of other classes of thiocarbonylthio compounds. These new organotin derivatives are efficient reversible chain-transfer agents for reversible addition-fragmentation chain transfer (RAFT) polymerization of styrene (St) and n-butyl acrylate (BA), with controlled number-average molecular weights and narrow dispersities (Ð<1.3). In some cases, loss of control of the polymerization was evidenced and supported by the observation of side products by 119 Sn NMR spectroscopy. This phenomenon was attributed to the thermal instability of the Sn-RAFT terminal group.

Phosphinoyl and thiophosphinoylcarbodithioates: synthesis, molecular structure, and application as new efficient mediators for RAFT polymerization.

New phosphinoyl and thiophosphinoylcarbodithioates were synthesized in a one-pot reaction from the corresponding phosphinochalcogenides. Compounds of this new generation of thiocarbonylthio derivatives have been fully characterized by IR as well as (1)H, (31)P, and (13)C NMR spectroscopy and by mass spectrometry. Their solid-state structures reveal that they are isostructural but crystallize in different space groups. These new compounds are highly efficient reversible chain-transfer agents for the reversible addition-fragmentation chain transfer (RAFT) polymerization of styrene (St) and n-butyl acrylate (nBA), with controlled number-average molecular weights (Mn) and narrow dispersity values (Ð<1.3). The controlled character of the polymerization was further exemplified by MALDI-TOF mass spectrometry and the synthesis of PSt-P(nBA) diblock copolymers.

Selective and Quantitative Oxidation of Xanthate End-Groups of RAFT Poly(n-butyl acrylate) Latexes by Ozonolysis.

Although various successful strategies have been reported in the past for the postpolymerization modification of the reversible addition-fragmentation chain transfer (RAFT) terminal group in homogeneous media, no solution is proposed for the tedious case of aqueous polymer dispersions where most of the thiocarbonylthio terminal group is buried into the core of the polymer particle. In this work, ozone is proposed to tackle this important academic and industrial challenge. After preliminary model ozonolysis reactions performed on a xanthate RAFT agent and a derived low molar mass poly(n-butyl acrylate) (PBA) in dichloromethane solution, it is shown that the hydrophobic nature and strong oxidant properties of ozone are responsible for its efficient diffusion in aqueous PBA latex particles obtained by RAFT and selective and complete transformation of the xanthate terminal group into a thiocarbonate end-group. In addition to the beneficial total discoloration of the final product, this chemical treatment does not generate any volatile organic compound and leaves the colloidal stability of the polymer particles unaffected, provided that a PBA latex with a sufficiently high Mn of 5000 g mol(-1) is selected.

Highly stable layered double hydroxide colloids: a direct aqueous synthesis route from hybrid polyion complex micelles.

Aqueous suspensions of highly stable Mg/Al layered double hydroxide (LDH) nanoparticles were obtained via a direct and fully colloidal route using asymmetric poly(acrylic acid)-b-poly(acrylamide) (PAA-b-PAM) double hydrophilic block copolymers (DHBCs) as growth and stabilizing agents. We showed that hybrid polyion complex (HPIC) micelles constituted of almost only Al(3+) were first formed when mixing solutions of Mg(2+) and Al(3+) cations and PAA3000-b-PAM10000 due to the preferential complexation of the trivalent cations. Then mineralization performed by progressive hydroxylation with NaOH transformed the simple DHBC/Al(3+) HPIC micelles into DHBC/aluminum hydroxide colloids, in which Mg(2+) ions were progressively introduced upon further hydroxylation leading to the Mg-Al LDH phase. The whole process of LDH formation occurred then within the confined environment of the aqueous complex colloids. The hydrodynamic diameter of the DHBC/LDH colloids could be controlled: it decreased from 530 nm down to 60 nm when the metal complexing ratio R (R = AA/(Mg + Al)) increased from 0.27 to 1. This was accompanied by a decrease of the average size of individual LDH particles as R increased (for example from 35 nm at R = 0.27 down to 17 nm at R = 0.33), together with a progressive favored intercalation of polyacrylate rather than chloride ions in the interlayer space of the LDH phase. The DHBC/LDH colloids have interesting properties for biomedical applications, that is, high colloidal stability as a function of time, stability in phosphate buffered saline solution, as well as the required size distribution for sterilization by filtration. Therefore, they could be used as colloidal drug delivery systems, especially for hydrosoluble negatively charged drugs.

1,1'- Thiocarbonyldiimidazole Radical Copolymerization for the Preparation of Degradable Vinyl Polymers.

1,1'-Thiocarbonyldiimidazole (TCDI) readily undergoes radical copolymerization with tert-butyl acrylate (tBA), N,N-dimethylacrylamide, and styrene. 1H NMR monitoring of the comonomer reactivity revealed a notable compatibility between TCDI and comonomers, resulting in similar consumption rates when TCDI was introduced at a 10% feed ratio. Furthermore, trithiocarbonate-mediated RAFT copolymerization of TCDI with tBA gave polymers that exhibited a linear increase of molar mass (Mnth = 2-10 kg mol-1) with conversion with relatively low dispersities (1.2-1.4). Importantly, this process enabled a successful chain extension of the produced P(TCDI-co-tBA) copolymer with styrene to form a diblock copolymer. The copolymers generated through this method contain TCDI-derived diimidazolyl thioether moieties, as established through 1H NMR spectroscopy. Additionally, degradation experiments using isopropylamine, benzoyl peroxide, sodium methoxide, and bleach have provided further confirmation of the presence of degradable TCDI moieties in the vinyl copolymer backbone.

Morphology and thermal transitions of self-assembled NIPAM-DMA copolymers in aqueous media depend on copolymer composition profile.

HYPOTHESIS: There is a lack of understanding of the interplay between the copolymer composition profile and thermal transition observed in aqueous solutions of N-isopropyl acrylamide (NIPAM) copolymers, as well as the correlation between this transition and the formation and structure of copolymer self-assemblies. EXPERIMENTS: For this purpose, we investigated the response of five copolymers with the same molar mass and chemical composition, but with different composition profile in aqueous solution against temperature. Using complementary analytical techniques, we probed structural properties at different length scales, from the molecular scale with Nuclear Magnetic Resonance (NMR) to the colloidal scale with Dynamic Light Scattering (DLS) and Small Angle Neutron Scattering (SANS). FINDINGS: NMR and SANS investigations strengthen each other and allow a clear picture of the change of copolymer solubility and related copolymer self-assembly as a function of temperature. At the molecular scale, dehydrating NIPAM units drag N,N-dimethyl acrylamide (DMA) moieties with them in a gradual collapse of the copolymer chain; this induces a morphological transition of the self-assemblies from star-like nanostructures to crew-cut micelles. Interestingly, the transition spans a temperature range which depends on the monomer distribution profile in the copolymer chain, with the asymmetric triblock copolymer specimen revealing the broadest one. We show that the broad morphological transitions associated with gradient copolymers can be mimicked and even surpassed by the use of stepwise gradient (asymmetric) copolymers, which can be more easily and reproducibly synthesized than linear gradient copolymers.

Vanillin-Based Epoxy Vitrimers: Looking at the Cystamine Hardener from a Different Perspective.

Epoxy vitrimers encompass many advantages compared to traditional epoxy materials such as recyclability, repairability, and reprocessability. These properties are induced by the incorporation of dynamic reversible covalent bonds. Recently, the incorporation of aromatic disulfide bridges that are dynamic has expanded the development of new eco-friendly epoxy materials. Herein, we studied a bio-based aliphatic disulfide based on cystamine as a hardener with a vanillin-derived bio-sourced epoxy to prepare fully bio-based epoxy vitrimers. This article provides a comparative study between cystamine and an aromatic disulfide benchmark hardener issued from petrol resources. This work demonstrated that the presence of this aliphatic hardener has a significant influence not only on the reactivity, but most importantly on the resulting dynamic properties. An interesting yet counterintuitive accelerating effect of the dynamic exchanges was clearly demonstrated with only 2 to 20% of molar fraction of cystamine added to the aromatic disulfide formulation. A similar glass transition was obtained compared to the purely aromatic analogue, but relaxation times were decreased by an order of magnitude.

Diblock versus block-random copolymer architecture effect on physical properties of Gd3+-based hybrid polyionic complexes.

HYPOTHESIS: Random insertion of vinylphosphonic acid (VPA) units into a of PEG-PAA block copolymer improves the chemical stability and properties of hybrid nanoobjects obtained from the complexation of the copolymer with metal ions. EXPERIMENTS: Block polymers based on poly(acrylic acid) (PAA) and poly(ethylene glycol) (PEG) are modified by random insertion of 0 to 100 % of phosphonic acid functions in PAA block by a RAFT polymerization process. These polymers are then used to form hybrid polyionic complexes (HPICs) by complexation with gadolinium or europium ions. The properties of the obtained assemblies are evaluated by magnetic relaxivity, fluorescence and light scattering measurements. FINDINGS: The insertion of VPA units within the PAA block increases the chemical stability of the hybrid micelles by maintaining their integrity even at low pH. This insertion also minimizes the exchange of ions between HPICs and the surrounding medium thanks to a strengthening of interactions toward lanthanide ions. When such systems are used as MRI contrast agents or luminescent probe, 50/50 AA/VPA composition appears to be a good compromise to achieve optimal relaxivity or luminescent properties while ensuring a good chemical stability.

Exploring the Limits of High-Tg Epoxy Vitrimers Produced through Resin-Transfer Molding.

Over the past few years, scientists have developed new ways to overcome the recycling issues of conventional thermosets with the introduction of associative covalent adaptable networks (i.e., vitrimers) in polymer materials. Even though various end-use vitrimers have already been reported, just a few of them have targeted high-performance industrial applications. Herein, we develop a promising high-performance epoxy vitrimer based on a commercially available resin widely used in aeronautics with the highest glass transition temperature (Tg) of 233 °C ever reported for a vitrimer. A complete study of its physicochemical properties and cure kinetics was conducted, enabling the construction of the first time-temperature-transformation (TTT) diagram reported in the literature. This diagram allows a full determination of the processing and curing parameters leading to the manufacturing of vitrimer samples by the resin-transfer molding (RTM) process. The reshapability and limits therefrom of this high-Tg vitrimer were evaluated by three successful thermoforming cycles without degradation.

Assemblies of poly(N-vinyl-2-pyrrolidone)-based double hydrophilic block copolymers triggered by lanthanide ions: characterization and evaluation of their properties as MRI contrast agents.

Because of the formation of specific antibodies to poly(ethylene glycol) (PEG) leading to life-threatening side effects, there is an increasing need to develop alternatives to treatments and diagnostic methods based on PEGylated copolymers. Block copolymers comprising a poly(N-vinyl-2-pyrrolidone) (PVP) segment can be used for the design of such vectors without any PEG block. As an example, a poly(acrylic acid)-block-poly(N-vinyl-2-pyrrolidone) (PAA-b-PVP) copolymer with controlled composition and molar mass is synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. Mixing this copolymer with lanthanide cations (Gd3+, Eu3+, Y3+) leads to the formation of hybrid polyion complexes with increased stability, preventing the lanthanide cytotoxicity and in vitro cell penetration. These new nanocarriers exhibit enhanced T1 MRI contrast, when intravenously administered into mice. No leaching of gadolinium ions is detected from such hybrid complexes.

Enhancement of poly(vinyl ester) solubility in supercritical CO2 by partial fluorination: the key role of polymer-polymer interactions.

An enhancement of poly(vinyl ester) solubility in supercritical carbon dioxide (sc-CO(2)) can be achieved by decreasing the strength of the polymer-polymer interactions. To demonstrate this, a library of statistical copolymers of vinyl acetate and vinyl trifluoroacetate was synthesized by RAFT/MADIX polymerization with varying compositions at a given number-average molecular weight. These copolymers exhibited unprecedentedly low cloud-point pressures in sc-CO(2) at 40 °C compared with previously reported poly(vinyl esters). Surface tension measurements combined with a computational approach evidenced the prominent role played by polymer-polymer interactions.