Reversible Addition-fragmentation Chain Transfer Research Articles

Jeffamine-based diblock copolymer nanoparticles via reverse sequence polymerization-induced self-assembly in aqueous media

Jeffamines® are commercially available amine-capped poly (alkylene oxides) that have been used for various applications. In this study, a weakly hydrophobic monoamine-capped propylene oxide-rich Jeffamine® (M2005) is derivatized to introduce a trithiocarbonate end-group via amidation. This precursor is then dissolved using N,N′-dimethylacrylamide (DMAC), 2-(N-acryloyloxy)ethyl pyrrolidone (NAEP) or N-acryloylmorpholine (NAM) as a co-solvent to produce a concentrated aqueous reaction mixture containing 20 % w/w water. Subsequently, reversible addition-fragmentation chain transfer (RAFT) polymerization is used to prepare Jeffamine®-core diblock copolymer nanoparticles by reverse sequence polymerization-induced self-assembly (PISA). At intermediate conversion, additional degassed water is added and each polymerization continues to almost full conversion (>99 %) within 4 h at 60 °C, resulting in a 10–20 % w/w aqueous dispersion of sterically-stabilized Jeffamine®-core nanoparticles. Efficient chain extension of the Jeffamine® precursor is achieved in most cases and relatively narrow molecular weight distributions are obtained (Mw/Mn < 1.30) as judged by GPC analysis. Transmission electron microscopy studies confirm a polydisperse spherical morphology and dynamic light scattering studies report hydrodynamic diameters ranging from 145 to 312 nm. Finally, aqueous electrophoresis studies indicate essentially neutral nanoparticles over a wide range of solution pH, as expected for the three types of non-ionic steric stabilizer chains selected for this study.

Antibacterial Nanoplatelets via Crystallization-Driven Self-Assembly of Poly(l-lactide)-Based Block Copolymers.

Membrane-active antimicrobial materials are promising substances to fight antimicrobial resistance. Herein, crystallization-driven self-assembly (CDSA) is employed for the preparation of nanoparticles with different morphologies, and their bioactivity is explored. Block copolymers (BCPs) featuring a crystallizable and antimicrobial block were synthesized using a combination of ring-opening and photoiniferter RAFT polymerizations. Subsequently formed nanostructures formed by CDSA could not be deprotected without degradation of the structures. CDSA of deprotected BCPs yielded 2D diamond-shaped nanoplatelets in MeOH, while spherical nanostructures were observed for assembly in water. Platelets exhibited improved antibacterial capabilities against two Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) compared to their spherical counterparts. The absence of hemolytic activity leads to the excellent selectivity of platelets. A mechanism based on membrane permeabilization was confirmed via dye-leakage assays. This study emphasized the impact of the shape of nanostructures on their interaction with bacterial cells and how a controlled assembly can improve bioactivity.

A Minimalist Method for Fully Oxygen-Tolerant RAFT Polymerization through Sulfur-Centered Trithiocarbonate Radical Initiation.

In recent years, the fully oxygen-tolerant reversible deactivation radical polymerization (RDRP) has become a highly researched area. In this contribution, a new and minimalist method is successfully employed to accomplish fully oxygen-tolerant reversible addition-fragmentation chain transfer (RAFT) polymerization using bis(trithiocarbonate) disulfides (BisTTC) as an iniferter agent, where the released sulfur-centered trithiocarbonate (TTC) radical can initiate monomer. Furthermore, polymerization kinetics revealed the typical "living" features of this polymerization system. More importantly, by high-throughput screening, it is found that dodecyl-substituted TTC is responsible for the fully oxygen-tolerant RAFT polymerization though trithiocarbonate radical initiation and R radical deoxygenation. It is believed that trithiocarbonate radical initiation strategy provides a powerful and minimalist tool for fully oxygen-tolerant RDRPs.

Esterified styrene-maleic acid copolymer modified silica as mixed-mode polymer-brush stationary phases for chromatographic separation

Styrene-maleic acid (SMA) copolymer has received much attention for its excellent solubilization characteristics. In this work, SMA copolymer brush-based chromatographic stationary phases were exploited and developed for the first time. First, SMA copolymer brush was in situ grown on the surface of spherical silica via living/controlled reversible addition-fragmentation chain transfer (RAFT) polymerization method. Subsequently, as a proof-of-concept demonstration, the copolymer was esterified by diethylene glycol mono-2-ethylhexyl ether (DGME) and 2-(2-ethylhexyloxy) ethanol (EHOE), respectively. The obtained Sil-SMA-DGME and Sil-SMA-EHOE copolymer-brush chromatographic stationary phases were characterized by transmission electron microscopy, Fourier transform infrared spectrometer, X-ray photoelectron spectroscopy, and thermogravimetric analysis, respectively. The chromatographic retention mechanism indicated that both the two packed columns exhibited hydrophilic/reverse mixed-mode retention modes. The maximum column efficiency was up to 71,000 N/m. The chromatographic separation performance evaluation indicated that the novel kind of stationary phases had excellent separation capabilities for hydrophilic, hydrophobic compounds and phospholipid standards. In addition, by combination with mass spectrometry identification, the Sil-SMA-DGME column was further exploited for separation and identification of phospholipids in human lung cancer cells. Totally, 9 classes including 186 phospholipid species were successfully identified. The results demonstrated the promising application prospects of the novel kind of SMA copolymer-brush chromatographic stationary phases.

One-Pot Preparation of Ratiometric Fluorescent Molecularly Imprinted Polymer Nanosensor for Sensitive and Selective Detection of 2,4-Dichlorophenoxyacetic Acid.

The development of fluorescent molecular imprinting sensors for direct, rapid, and sensitive detection of small organic molecules in aqueous systems has always presented a significant challenge in the field of detection. In this study, we successfully prepared a hydrophilic colloidal molecular imprinted polymer (MIP) with 2,4-dichlorophenoxyacetic acid (2,4-D) using a one-pot approach that incorporated polyglycerol methacrylate (PGMMA-TTC), a hydrophilic macromolecular chain transfer agent, to mediate reversible addition-fragmentation chain transfer precipitation polymerization (RAFTPP). To simplify the polymerization process while achieving ratiometric fluorescence detection, red fluorescent CdTe quantum dots (QDs) and green fluorescent nitrobenzodiazole (NBD) were introduced as fluorophores (with NBD serving as an enhancer to the template and QDs being inert). This strategy effectively eliminated background noise and significantly improved detection accuracy. Uniform-sized MIP microspheres with high surface hydrophilicity and incorporated ratiometric fluorescent labels were successfully synthesized. In aqueous systems, the hydrophilic ratio fluorescent MIP exhibited a linear response range from 0 to 25 μM for the template molecule 2,4-D with a detection limit of 0.13 μM. These results demonstrate that the ratiometric fluorescent MIP possesses excellent recognition characteristics and selectivity towards 2,4-D, thus, making it suitable for selective detection of trace amounts of pesticide 2,4-D in aqueous systems.

Photoresponsive Block Copolymer Nanostructures through Implementation of Arylazopyrazoles.

Responsive nanomaterials that can undergo reversible changes in morphology are interesting for the development of functional materials that interact with and respond to their environment. Amphiphilic block copolymers are well-known for their ability to create a wide range of supramolecular nanostructures in solution. Arylazopyrazoles (AAPs) are versatile molecular photoswitches, which change their configuration and hydrophobicity upon irradiation with UV light (365 nm, Z isomer, less hydrophobic) and green light (520 nm, E isomer, more hydrophobic). In this work, photoswitchable block copolymers containing arylazopyrazole tetraethylene glycol methacrylate (AAPMA) and oligo(ethylene glycol) methacrylate (OEGMA) forming amphiphilic POEGMA-b-PAAPMA with varying block lengths are prepared by RAFT polymerization. The photochemical properties of AAP persist in the polymers. Due to their amphiphilic structure, the polymers self-assemble into supramolecular morphologies in water. Remarkably, photoisomerization results in a reversible change in the self-assembly behavior. Specifically, spherical and cylindrical micelles are observed for POEGMA33-b-PAAPMA47 when illuminated with green or UV light during assembly. Furthermore, the morphology of assembled structures can be reversibly switched by subsequent irradiation with UV and green light.

A series of tetraphenylene-acetonitrile AIE compounds with D-A-D′ structure for drugs delivery systems of paclitaxel: Synthesis, structure-activity relationship and anti-tumors effect

Aggregation-induced emission (AIE) materials are attracting great attention in biomedical fields such as sensors, bioimaging, and cancer treatment, et al. due to their strong fluorescence emission in the aggregated state. In this contribution, a series of tetraphenylene-acetonitrile AIE compounds with D-A-D′ structures were synthesized by Suzuki coupling reaction and Knoevenagel condensation, and their relationship of chemical structure and fluorescence properties was investigated in detail, among which TPPA compound was selected as the monomer owing to the longest emission wavelength at about 530 nm with low energy band gap ΔE 3.09 eV of neutral TPPA and 1.43 eV of protonated TPPA. Novel amphiphilic AIE PEG-TA copolymers were prepared by RAFT polymerization of TPPA and PEGMA with about 1.44×104 Mw and narrow PDI, and the molar ratio of TPPA in the PEG-TA1 and PEG-TA2 copolymers was about 23.4 % and 29.6 %. The as-prepared PEG-TA copolymers would self-assembled in aqueous solution to form core-shell structures with a diameter of 150–200 nm, and their emission wavelength could reversibly convert from 545 nm to 650 nm with excellent pH sensitivity. The CLSM images showed that the PEG-TA FONs and PTX drugs-loaded PTX-TA FONs could be endocytosed by cells and mainly enriched in the cytoplasm, and CCK-8 results showed that the PEG-TA FONs had excellent biocompatibility but PTX-TA FONs had high inhibition ratio for A549 cells, moreover, the flow cytometry also showed that PTX-TA FONs could result in the apoptosis of A549 cells with some extent anti-tumor effect.

Preparation of Water-Soluble Polyion Complex (PIC) Micelles with pH-Responsive Carboxybetaine Block.

A dual zwitterionic diblock copolymer (M100C100) consisting of poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC, M) and poly(3-((2-(methacryloyloxy)ethyl) dimethylammonio) propionate) (PCBMA, C) is synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. A double hydrophilic diblock copolymer (M100S100) consist of PMPC and anionic poly(3-sulfopropyl methacrylate potassium salt) (PMPS, S) is synthesized via RAFT. The degrees of polymerization of each block are 100. The charges of PMPC are neutralized intramolecularly. At neutral pH, the charges in PCBMA are also neutralized intramolecularly due to its carboxybetaine structure. Under acidic conditions, PCBMA exhibits polycation behavior as the pendant carboxy groups become protonated, forming cationic tertiary amine groups. PMPS shows permanent anionic nature independent of pH. Charge neutralized mixture of cationic M100C100 and anionic M100S100 in acidic aqueous solution forms water-soluble polyion complex (PIC) micelle owing to electrostatic attractive interactions. The core is composed of the cationic PCBMA and anionic PMPS blocks, with the PMPC blocks serving as shells that covered the core surface, forming spherical core-shell PIC micelles. Above pH 4 the pendant carboxy groups in PCBMA undergo deprotonation, transitioning to a zwitterionic state, thereby eliminating the cationic charge in PCBMA. Therefore, above pH 4 the PIC micelles are dissociated due to the disappearance of the charge interactions.

Revealing into the formation mechanism of various nanostructures self-assembled from a bipyridine containing homopolymer

The control of the morphology and nanostructure of soft nanomaterials self-assembled from amphiphilic polymers has attracted significant attention. In this study, various nanostructures including bowl-shaped nanoparticles with controlled openings, round Yuanbao-shaped assemblies, nanowires and butterfly shaped twin nanosheets are formed by manipulating the self-assembly pathway of an amphiphilic homopolymer. The amphiphilic (poly(N-(2,2′-bipyridyl-4-acrylamide), PBPyAA) with bipyridine pendants is designed and synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization, which can self-assemble into bowl-shaped nanoparticles with controlled openings by solvent switch method at different initial concentrations. In addition, core–shell nanostructures are obtained taking advantage of the coordination between bipyridine and Fe2+. Upon annealing in ethanol, butterfly shaped twin nanosheets with thickness of about 10 nm are formed by controlling the cooling rate, while round Yuanbao-shaped assemblies are formed by naturally cooling. Revealing into the formation mechanism of the butterfly shaped twin nanosheets, a fusion induced assembly process of nanowires is observed. Overall, various nanostructures are obtained by manipulating the self-assembly pathways of a bipyridine containing amphiphilic homopolymer.

Synthesis and rheological analyzes of temperature and light sensitive gels comprising amphiphilic azobenzene polymers, chitosan and pluronic F127

AbstractThis study investigates the reinforcement of pluronic (PF127) based temperature responsive hydrogels with photosensitive functionalities to create smart and injectable materials. For this purpose, 4‐[4‐[(4‐phenyl)azo]phenoxy] methacrylate (PAzPMA) was synthesized and further polymerized via reversible addition‐fragmentation chain transfer (RAFT) polymerization. The structures of the copolymers were characterized by several techniques such as Fourier‐transform infrared (FT‐IR), nuclear magnetic resonance (NMR) spectroscopy and gel permeation chromatography (GPC). The azobenzene‐functionalized copolymer was combined with P127 solid polymer in micelle form and with P127 micelles in solid form to obtain PF127‐AzoMx and PF127‐AzoPx gels, respectively. When the temperature profiles of the PF127‐AzoMx and PF127‐AzoPx systems were compared with PF127, sol–gel phase transition were shifted to lower temperatures due to stronger hydrophobic interactions. Additionally, different concentrations of N,N,N‐trimethyl chitosan (f‐chitosan) were added to the gel systems and their rheological properties were investigated by exposing them to UV light. It has been observed that the presence and concentration of f‐chitosan are important for the variation of the interactions' strength between the micelles. The study highlights the potential of multifunctional hydrogels for specific biomedical applications that combine sensitivity to both thermal and optical stimuli for controlled drug delivery and tissue engineering purposes.

Synthesis and Performance of Polycarboxylate Ether Superplasticizers with Controlled Structure via RAFT Polymerization

Synthesis and Performance of Polycarboxylate Ether Superplasticizers with Controlled Structure via RAFT Polymerization

Microphase Separation and Gelation through Polymerization-Induced Self-Assembly Using Star Polyethylene Glycols.

Polymerization-induced self-assembly (PISA) during the synthesis of diblock copolymers has garnered considerable interest; however, architectures beyond diblock copolymers have scarcely been explored. Here, we studied PISA using 4- and 8-arm star polyethylene glycol (PEG), as well as 2-arm (linear) PEG, wherein each terminus of PEG was functionalized with a chain-transfer agent, holding a constant molar mass for each arm. Styrene was polymerized from each PEG terminus through reversible addition-fragmentation chain-transfer (RAFT) polymerization in an ionic liquid (1-butyl-3-methylimidazolium hexafluorophosphate, [BMIM][PF6]), with a total solute concentration of 40 wt %. While the styrene monomer is soluble in [BMIM][PF6], polystyrene is not; thus, self-assembly and cross-linking (gelation) occur. Structural analysis by small-angle X-ray scattering revealed that a relatively ordered microphase-separated structure for PISA was observed. Two-arm PEG-PS formed hexagonally packed cylinders, whereas 4- and 8-arm PEG-PS exhibited hexagonal close-packed spheres and disordered spheres. The dynamics, studied by oscillatory rheology, were also influenced by the number of arms; the 4-arm star block copolymers showed the highest plateau modulus. This study demonstrates that the topology is an important factor in controlling the microphase-separated structure and mechanical properties when preparing gels through PISA.

Self-Assembly of Hydrophobic Hyperbranched PLMA Homopolymer with -COOH End Groups as Effective Nanocarriers for Bioimaging Applications.

Nanomedicine is a discipline of medicine that applies all aspects of nanotechnology strategies and concepts for treatment and screening possibilities. Synthetic polymer nanostructures are among the many nanomedicine formulations frequently studied for their potential as vectors. Bioimaging is a valuable diagnostic tool, thus, there is always a demand for new excipients/nanocarriers. In this study, hydrophobic hyperbranched poly(lauryl methacrylate) (PLMA) homopolymers comprised of highly hydrophobic LMA moieties with -COOH polar end groups were synthesized by employing reversible addition-fragmentation chain transfer (RAFT) polymerization. Ethylene glycol dimethacrylate (EGDMA) was utilized as the branching agent. End groups are incorporated through the RAFT agent utilized. The resulting amphiphilic hyperbranched polymer was molecularly characterized by size exclusion chromatography (SEC), Fourier transformation infrared spectroscopy (FT-IR), and 1H-NMR spectroscopy. Pyrene, curcumin, and IR-1048 dye were hydrophobic payload molecules successfully encapsulated to show how adaptable these homopolymer nanoparticles (prepared by nanoprecipitation in water) are as dye nanocarriers. This study demonstrates a simple way of producing excipients by generating polymeric nanoparticles from an amphiphilic, hyperbranched, hydrophobic homopolymer, with a low fraction of polar end groups, for bioimaging purposes.

Aqueous RAFT Dispersion Polymerization Mediated by an ω,ω-Macromolecular Chain Transfer Monomer: An Efficient Approach for Amphiphilic Branched Block Copolymers and the Assemblies.

Herein, an ω,ω-macromolecular chain transfer monomer (macro-CTM) containing a RAFT (reversible addition-fragmentation chain transfer) group and a methacryloyl group was synthesized and used to mediate photoinitiated RAFT dispersion polymerization of hydroxypropyl methacrylate (HPMA) in water. The macro-CTM undergoes a self-condensing vinyl polymerization (SCVP) mechanism under RAFT dispersion polymerization conditions, leading to the formation of amphiphilic branched block copolymers and the assemblies. Compared with RAFT solution polymerization, it was found that the SCVP process was promoted under RAFT dispersion polymerization conditions. Morphologies of branched block copolymer assemblies could be controlled by varying the monomer concentration and the [HPMA]/[macro-CTM] ratio. The branched block copolymer vesicles could be used as seeds for seeded RAFT emulsion polymerization, and framboidal vesicles were successfully obtained. Finally, degrees of branching of branched block copolymers could be further controlled by using a binary mixture of the macro-CTM and a linear macro-RAFT agent or a small molecule CTM. We believe that this study not only provides a versatile strategy for the preparation of branched block copolymer assemblies but also offers important insights into polymer synthesis via heterogeneous RAFT polymerization.

Phage probe on RAFT polymer surface for rapid enumeration of E. coli K12

This study presents a simple, fast, and sensitive label-free sensing assay for the precise enumeration of modeled pathogenic Escherichia coli K12 (E. coli K12) bacteria for the first time. The method employs the covalent binding bacteriophage technique on the surface of a reversible addition-fragmentation chain transfer (RAFT) polymer film. The Nyquist plots obtained from electrochemical impedance spectroscopy (EIS) identified the charge transfer resistance Rct was calculated from a suitable electrochemical circuit model through an evaluation of the relevant parameter after the immobilization of the bacteriophage and the binding of specific E. coli K12. The impedimetric biosensor reveals specific and reproducible detection with sensitivity in the linear working range of 104.2-107.0 CFU/mL, a limit of detection (LOD) of 101.3 CFU/mL, and a short response time of 15 min. The SERS response validates the surface roughness and interaction of the SERS-tag with E. coli K12-modified electrodes. Furthermore, the covalently immobilized active phage selectivity was proved against various non-targeting bacterial strains in the presence of targeted E.coli K12 with a result of 94 % specificity and 98 % sensitivity. Therefore, the developed phage-based electrode surface can be used as a disposable, label-free impedimetric biosensor for rapid and real-time monitoring of serum samples.

Synthesis of phosphorus fluorine containing polymers for flame-retardant, low surface energy and good dielectric performance epoxy resin electronic packaging materials

In order to satisfy the application of epoxy resin (EP) in high-end electronic packaging, phosphorus fluorine containing polymers were synthesized to simultaneously enhance the flame retardant, dielectric, and hydrophobic properties of EP. Through the reaction of 2-hydroxyethyl methacrylate and 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO), a monomer named HEMA-P was synthesized. By copolymerizing (2,2,2-trifluoroethyl methacrylate and 1H, 1H, 7H-dodecafluoroheptyl methacrylate) with HEMA-P through the typical reversible addition-fragmentation chain transfer (RAFT) polymerization, two phosphorus fluorine containing polymer modifiers named 3FOP and 12FOP with different lengths of fluorine side chain were obtained. The flame-retardant level of FOP/EP composites reached V-1 level. The limited oxygen index (LOI) values of 3FOP/EP and 12FOP/EP composites (10 wt% additive amount) increased to 33.6 ± 0.5 % and 32.8 ± 0.3 %, respectively, with corresponding peak heat release rates (pHRR) decreased by 37.8 % and 33.2 % compared with neat EP, suggesting the FOP modified EP composites have good flame retardant and smoke suppression effects. The mechanical properties of the FOP/EP composites can also be improved. Notably, with the 10 wt% addition of 12FOPs, the water contact angle of 12FOP/EP composite reached 116.5°, which was 40.7 % higher than that of EP. Moreover, the dielectric constant decreased with the increasing fluorine content. The thermal stability and possible thermal degradation pathways of 3FOP and 12FOP were characterized by TG-IR, Py-GC/MS, and Raman spectroscopy. Based on experimental results, we innovatively revealed a phosphorus fluorine synergistic flame retardancy mechanism.

Boosting catalytic efficiency of lipase by regulating amphiphilic microenvironment through reversible addition-fragmentation chain transfer polymerized modifications on polyacrylonitrile fiber

Lipases are increasingly attracting attention in green and sustainable biodiesel production. Currently, the research emphasis lies in immobilizing unstable lipase onto carriers to enhance its performance. Polyacrylonitrile fiber (PANF) is considered to be a promising material for lipase immobilization due to its excellent properties. In this study, functional carriers with regulated surface hydrophobicity were obtained by loading functional groups on PANF via reversible addition-fragmentation chain transfer (RAFT) polymerized modification, and Candida rugosa lipase (CRL) was covalently immobilized on the carrier with glutaraldehyde as a linker. By employing this optimized biocatalyst PANF@BMA&2VImBr-NH2-CRL in the transesterification process, the yield of biodiesel derived from soybean oil reached an impressive 92.7 %. The outstanding performance can be attributed to the activation of lipase interface induced by hydrophobic microenvironment derived from alkyl ester on the carrier skeleton. Moreover, the stability and storage performance of immobilized lipase were significantly improved. The immobilized lipase exhibited facile recovery and maintained a consistent biodiesel yield of 80.9 % even after undergoing 5 cycles of reuse, thereby highlighting its potential for sustainable production. To sum up, our research demonstrates that the designed and prepared process of PANF-supported lipase offers a promising approach for enzyme immobilization, thereby presenting extensive potential applications in the field of biotechnology.

Terpyridine-Decorated Polymer Nanosphere Latex: Template Nanocarriers for the Synthesis of Cu-CeO2 Hollow Spheres.

Water-soluble polymers with the ability to complex metal ions through complexing ligands have attracted significant interest in diverse domains, such as optical or catalyst applications. In this paper, we successfully synthesized, through a one-pot process combining polymerization-induced self-assembly and reversible addition-fragmentation chain transfer polymerization, aqueous dispersions of terpyridine-decorated poly[poly(ethylene glycol)methyl ether methacrylate]-b-poly(methyl methacrylate) (tpy-PPEGMA-b-PMMA) amphiphilic block copolymers. The in-situ formation of well-defined amphiphilic block copolymers and their self-assembly led to nanosphere latex with the hydrodynamic diameters increasing from 17 to 52 nm and the length of the copolymers increasing from 21,000 to 51,000 g·mol-1. These aqueous dispersed tpy-PPEGMA-b-PMMA nanospheres effectively complex metal ions, such as Cu2+, in a stoichiometric ratio of 2:1. Subsequently, these metal-complexed nanospheres were employed as soft template nanocarriers to control, on the nanometer scale, the dispersion of metal on a nanostructured support. This is exemplified by the synthesis of copper supported on cerium oxide hollow spheres (Cu-CeO2) using Cu2+-tpy-PPEGMA-b-PMMA as template nanocarriers and CeO2 nanoparticles. This novel assembly engineering strategy for the preparation of atomically dispersed metal on a nanostructured support was highlighted through the utilization of Cu-CeO2 hollow spheres as an electrocatalyst for the nitrate reduction reaction (NO3RR) to NH3. These encouraging outcomes emphasize the potential of metal-metal oxide-nanostructured materials to treat contaminated water sources with nitrate while allowing the green production of ammonia.

Exploiting the Reversible Dimerization of N-Heterocyclic Carbenes to Access Dynamic Polymer Networks with an Organocatalytic Activity.

The capability of some N-heterocyclic carbenes (NHCs) to reversibly dimerize is exploited to access dynamic polymer networks. Benzimidazolium motifs serving as NHC precursors have thus been supported onto copolymer chains by reversible addition-fragmentation chain transfer (RAFT) copolymerization of styrene and up to 20 mol % of 4-vinylbenzyl-ethyl-benzimidazolium chloride. Molecular versions of 1,3-dialkyl benzimidazolium salts have been synthesized as models, the deprotonation of which with a strong base yields the NHC dimers in the form of tetraaminoalkenes. The crossover reaction between two distinct NHC homodimers, forming heterodimers, is then evidenced. Applying this deprotonation method to the RAFT-derived copolymers leads to polymer networks with cross-links consisting of labile dimerized NHC motifs. These networks can be subsequently decross-linked using two distinct triggers, namely, a monofunctional NHC precursor as competitor and carbon dioxide (CO2). In the latter case, regeneration of the network occurs by chemically fueling the linear copolymer bearing benzimidazolium motifs with tBuOK in the presence of trace amounts of water. The same networks can also be used as latent precursors of transient polyNHCs to catalyze the benzoin condensation upon heating. The polymer-supported organocatalysts can thus be used in successive catalytic cycles.

Harnessing Guanidinium and Imidazole Functional Groups: A Dual-Charged Polymer Strategy for Enhanced Gene Delivery.

Histidine and arginine are two amino acids that exhibit beneficial properties for gene delivery. In particular, the imidazole group of histidine facilitates endosomal release, while the guanidinium group of arginine promotes cellular entry. Consequently, a dual-charged copolymer library based on these amino acids was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. The content of the N-acryloyl-l-histidine (His) monomer was systematically increased, while maintaining consistent levels of methyl N-acryloyl-l-argininate hydrochloride (ArgOMe) or N-(4-guanidinobutyl)acrylamide hydrochloride (GBAm). The resulting polymers formed stable, nanosized polyplexes when complexed with nucleic acids. Remarkably, candidates with increased His content exhibited reduced cytotoxicity profiles and enhanced transfection efficiency, particularly retaining this performance level at lower pDNA concentrations. Furthermore, endosomal release studies revealed that increased His content improved endosomal release, while ArgOMe improved cellular entry. These findings underscore the potential of customized dual-charged copolymers and the synergistic effects of His and ArgOMe/GBAm in enhancing gene delivery.