Chain Transfer Research Articles

Antimicrobial Activity of Copolymer Structures from Bio-Based Monomers.

The urgent need for new antimicrobial compounds has led scientists to explore antimicrobial peptides (AMPs) and antimicrobial polymers as solutions for multidrug resistance. In this study, we synthesized copolymers with cationic and hydrophobic moieties by free-radical polymerization (FRP) using a chain transfer agent to control molecular weights. The potential of natural products as part of the hydrophobic moiety was evaluated, along with variations in their monomer content (13-25%) and the molecular weight (MW) of the copolymer (5000-20,000 g·mol-1). Hydrophobicity was evaluated using the theoretical Log Poct values and surface areas (SAs). Biological assays included antimicrobial activity against Escherichia coli and Staphylococcus aureus standard strains, hemolytic activity in red blood cells (RBC), and cytotoxicity tests against HEK293T cells. Keys findings indicate that copolymers with tropolone moieties, lower MWs, and an optimal balance between hydrophobic and cationic moieties show a promising basis for future generations of antimicrobials.

Preparation and characterization of poly(ethylene glycol)-b-poly(tert-butyl methacrylate) micelles as potential nanocarriers for donepezil

Polymeric micelles were prepared for the delivery of donepezil, a leading Alzheimer’s disease drug, to enhance its transport across the blood–brain barrier (BBB). Poly(ethylene glycol)-b-poly(tert-butyl methacrylate) amphiphilic block copolymers were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymers were characterized by gel permeation chromatography and nuclear magnetic resonance spectroscopy. Empty and donepezil loaded polymer micelles were formed using the dialysis method and characterized by dynamic light scattering and transmission electron microscopy. Drug loading efficiency and release behavior were monitored using UV/Vis spectroscopy, and cytotoxicity was evaluated via colorimetric tests and impedance measurements. Additionally, the permeability of the nanocarriers across an in vitro BBB culture model was assessed. Drug-loaded micelles demonstrated similar permeability to free donepezil but offered sustained release and improved stability. This micellar delivery system holds significant potential for improving therapeutic outcomes in Alzheimer’s treatment by enhancing donepezil’s delivery across the BBB. Improved BBB permeability and sustained drug release could lead to more effective concentration of the drug in the brain, potentially reducing peripheral cholinergic side effects, such as nausea and vomiting, often observed with traditional donepezil administration. This could result in better patient compliance and improved cognitive outcomes, making this nanocarrier system a promising alternative for Alzheimer’s therapy.

Thermal behavior of polymers and copolymers based on plant oils with differing saturated and monounsaturated content

AbstractPlant oil‐based acrylic monomers from hydrogenated sunflower (HFM), palm (PMM) and castor (CSM) oils were polymerized to investigate the effect of chemical composition on polymer phase transitions at temperatures relevant to physiological range. While HFM and PMM possess a highly differing content of saturated palmitic and stearic acids combined with unsaturated fatty acids, CSM contains primarily fragments based on monounsaturated ricinoleic hydroxy acid (up to 90%). Differential scanning calorimetry (DSC) measurements indicate that polymers from PMM and HFM are both semicrystalline (with Tm = −6 and −13 °C, respectively), while poly(CSM) appears to be amorphous (Tg = −49 °C). Considering the similarity in polymers' molar mass (Mn = 16 000–20 000 g mol−1), the observed thermal transitions can be explained by the formation of ordered morphological domains due to the presence of saturated palmitic and stearic acid fractions in poly(PMM) and poly(HFM). For copolymers of CSM, PMM and HFM (80 wt% of monomer feed) with styrene, DSC data show two transitions corresponding to the mobility of long alkyl fatty acid side fragments and the macromolecular backbone. For copolymers of PMM and HFM, comparable values (−52.8 and −55.5 °C, respectively) were obtained, while the second transition for poly(CSM‐co‐styrene) appears at 35 °C. We attribute this higher value to the presence of hydroxyl groups in ricinoleic acid fragments of CSM serving as additional chain transfer sites and the formation of macromolecular fractions enriched with polystyrene fragments. We expect that the temperature transitions obtained can be relevant to the future use of these polymers for biomedical applications, including the synthesis of polymer brushes. © 2024 Society of Chemical Industry.

Catalytic Syntheses of Thiol-End-Functionalized ROMP Polymers.

Thiol-functionalized polymers have become a crucial class of materials due to their distinct chemical properties and versatile reactivity, leading to a broad spectrum of applications. Herein, we report the straightforward syntheses of a wide range of thiol-end-functionalized ring-opening metathesis polymerization (ROMP) polymers exploiting our previously reported catalytic ROMP mechanisms using suitable chain transfer agents. All the synthesized polymers were characterized via SEC, 1H NMR spectroscopy and MALDI-ToF mass spectrometry techniques. Furthermore, the existence of thiol groups on the polymer chains was verified through the well-established thiol coating reaction on gold nanoparticle surfaces. We believe this method of synthesizing thiol-end-functionalized ROMP polymers (using a reduced amount of ruthenium metal compared to conventional living ROMP) will be of great importance to materials science and biochemical research.

Double Hydrophilic Hyperbranched Copolymer-Based Lipomer Nanoparticles: Copolymer Synthesis and Co-Assembly Studies

Double hydrophilic, random, hyperbranched copolymers were synthesized via reversible addition–fragmentation chain transfer (RAFT) polymerization of oligo(ethylene glycol) methyl ether methacrylate (OEGMA) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) utilizing ethylene glycol dimethacrylate (EGDMA) as the branching agent. The resulting copolymers were characterized in terms of their molecular weight and dispersity using size exclusion chromatography (SEC), and their chemical structure was confirmed using FT-IR and 1H-NMR spectroscopy techniques. The choice of the two hydrophilic blocks and the design of the macromolecular structure allowed the formation of self-assembled nanoparticles, partially due to the pH-responsive character of the DMAEMA segments and their interaction with -COOH end groups remaining from the chain transfer agent. The copolymers showed pH-responsive properties, mainly due to the protonation–deprotonation equilibria of the DMAEMA segments. Subsequently, a nanoscopic polymer–lipid (lipomer) mixed system was formulated by complexing the synthesized copolymers with cosmetic amphiphilic emulsifiers, specifically glyceryl stearate (GS) and glyceryl stearate citrate (GSC). This study aims to show that developing lipid–polymer hybrid nanoparticles can effectively address the limitations of both liposomes and polymeric nanoparticles. The effects of varying the ionic strength and pH on stimuli-sensitive polymeric and mixed polymer–lipid nanostructures were thoroughly investigated. To achieve this, the structural properties of the hybrid nanoparticles were comprehensively characterized using physicochemical techniques providing insights into their size distribution and stability.

Mechanistic Insights into the cis-Selective Catalytic Ring-Opening Metathesis Polymerization.

Cis-selective ring-opening metathesis polymerization (ROMP) with the commercial Grubbs "nitrato catalyst" has shown promise for synthesizing stereoregular materials, but it comes with the drawback of losing control over the molecular weight due to the poor initiation rate of the catalyst and the need for stoichiometric ruthenium complex loading. To address these issues, we developed a chain transfer polymerization method that allows for the catalytic synthesis of polymers while controlling the degree of polymerization. This allowed us to produce shorter polymers with exceptional chain-end control. Analysis of the polymers revealed a novel double monomer addition mechanism for this catalyst. MALDI-ToF mass spectrometric measurements showed that when using small monomers like norbornene, the polymer chains contained only odd numbers of monomers. In contrast, the polymerization of norbornene-imide-type monomers shows a major distribution with odd numbers of monomers along with a minor distribution of even numbers. This unique distribution of polymer chain types had not been previously observed in ROMP. We explain this phenomenon by the chiral nature of the catalyst that yields two isomeric catalytic species with dissimilar reactivities toward monomer and chain transfer agents.

Reversible addition-fragmentation chain transfer enhanced aggregation signal-on fluorescence detection of alkaline phosphatase.

The instability of the signal intensity of fluorescent biosensors and the false signals have been significant factors affecting the performance of biosensors. Herein, a novel signaling system is devised through the application of reversible addition-fragmentation chain transfer (RAFT) polymerization with monomers containing the tetraphenylethylene (TPE) groups. TPE exhibits an aggregation-induced emission (AIE) phenomenon in certain solvents, mainly due to the blockage of the rotation of its four benzene rings, which also exist in the aggregated state. With this property, a series of molecules are modified based on click chemistry for RAFT polymerization using Fe3O4 magnetic beads as the carriers, and stable aggregated luminescent TPE polymers are formed on the surface of magnetic beads to realize the transformation of fluorescence signal from "0" to "1". In addition, the fluorescence signal demonstrates a positive correlation with alkaline phosphatase (ALP) activity, which can be quantified by measuring the fluorescence intensity. The biosensor exhibits high sensitivity and good linearity in the range of 0.1-5 U/L, with a LOD of 0.079 U/L. Furthermore, the designed strategy demonstrated satisfactory performance in the quantitative determination of ALP activity in serum samples, indicating that the signaling system developed by combining RAFT polymerization and AIE molecules has an important application in the field of fluorescent biosensors.

Full on-device manipulation of olefin metathesis for precise manufacturing.

Olefin metathesis, as a powerful metal-catalysed carbon-carbon bond-forming method, has achieved considerable progress in recent years. However, the complexity originating from multicomponent interactions has long impeded a complete mechanistic understanding of olefin metathesis, which hampers further optimization of the reaction. Here, we clarify both productive and hidden degenerate pathways of ring-closing metathesis by focusing on one individual catalyst, using a sensitive single-molecule electrical detection platform. In addition to visualizing the full pathway, we found that the conventionally unwanted degenerate pathways have an unexpected constructive coupling effect on the productive pathway, and both types of pathway can be regulated by an external electric field. We then pushed forward this ability to ring-opening metathesis polymerization involving more interactive components. With single-monomer-insertion-event resolution, precise on-device synthesis of a single polymer was achieved by online manipulation of monomer insertion dynamics, intramolecular chain transfer, stereoregularity, degree of polymerization and block copolymerization. These results offer a comprehensive mechanistic understanding of olefin metathesis, exemplifying infinite opportunities for practical precise manufacturing.

RAFT Polymerization for Advanced Morphological Control: From Individual Polymer Chains to Bulk Materials.

Control of the morphology of polymer systems is achieved through reversible-deactivation radical polymerization techniques such as Reversible Addition-Fragmentation chain Transfer (RAFT). Advanced RAFT techniques offer much more than just "living" polymerization - the RAFT toolkit now enables morphological control of polymer systems across many decades of length-scale. Morphological control is explored at the molecular-level in the context of syntheses where individual monomer unit insertion provides sequence-defined polymers (single unit monomer insertion, SUMI). By being able to define polymer architectures, the synthesis of bespoke shapes and sizes of nanostructures becomes possible by leveraging self-assembly (polymerization induced self-assembly, PISA). Finally, it is seen that macroscopic materials can be produced with nanoscale detail, based on phase-separated nanostructures (polymerization induced microphase separation, PIMS) and microscale detail based on 3D-printing technologies. RAFT control of morphology is seen to cross from molecular level to additive manufacturing length-scales, with complete morphological control over all length-scales.

Precise Control of Molecular Weight Characteristics of Charge-Shifting Poly(2-(N,N-Dimethylamino)Ethylacrylate) Synthesized by Reversible Addition-Fragmentation Chain Transfer Polymerization.

Poly(2-(N,N-dimethylamino)ethyl acrylate) (PDMAEA) is a promising charge-shifting polycation with the capacity to form a range of morphologically distinct polyelectrolyte assemblies. Nevertheless, the basic character of the monomer and its hydrolytic instability impedes its controlled synthesis to higher molecular weight (MW). Herein, the reversible addition-fragmentation chain transfer polymerization of DMAEA is reported using a tert-butanol/V70 initiator/trithiocarbonate-based chain transfer agent (CTA) polymerization setup. The CTA instability is demonstrated in the presence of the unprotonated tertiary amino group of the DMAEA monomer, which limits the control over the conversion and MW of the polymer. In contrast, the shielding of the amino groups by their protonation leads to polymerization with high conversions and excellent control over MWs of polymer up to 100000g mol-1. Hydrolytic degradation study at pH values ranging from 5 to 9 reveals that both basic and protonated PDMAEA undergo a pH-dependent hydrolysis. The proposed polymerization conditions provide a means of synthesizing PDMAEA with well-controlled characteristics, which are beneficial for controlling the complexation processes during the formation of various polyelectrolyte assemblies.

Synthesis and Binding Properties of High-Affinity Histidine-Bearing Polymers for Wood Lignin.

The pursuit of molecules capable of binding to wood lignin is pivotal for advancing lignin degradation technology, particularly when combined with lignin degradation catalysts. In this study, synthetic polymers bearing histidine moieties, demonstrating remarkable affinity for wood lignin are reported. These polymers, featuring varying degrees of histidine substitution in the form of histidine methyl esters, are synthesized through controlled radical polymerization of an activated ester-bearing monomer, employing a fluorescein-labeled chain transfer agent and subsequent postpolymerization amidation with histidine methyl ester. The binding properties of these histidine-bearing polymers with milled wood lignin under aqueous conditions are investigated. Qualitative assessment of lignin-binding capabilities involve spectroscopic analysis of changes in absorbance of visible light and fluorescence intensity. Furthermore, quantitative evaluation is conducted through surface plasmon resonance measurements to determine the binding parameters of the polymers with wood lignin. Notably, polymers with higher histidine substitution exhibit enhanced binding affinity compared to those with lower histidine substitution levels.

Fluorocarbon-Functionalized Polymerization-Induced Self-Assembly Nanoparticles Alleviate Hypoxia to Enhance Sonodynamic Cancer Therapy.

Sonodynamic therapy (SDT) is an ultrasound-based, noninvasive cancer treatment that targets tumor cells by triggering reactive oxygen species production. However, the limited accumulation of sonosensitizers and the insufficient supply of O2 to the hypoxic environment at the tumor site greatly limit the effectiveness of SDT. To address these issues, positively charged porphyrin-containing nanoparticles (NPs) from self-assembling of fluorocarbon/polyethylene glycol amphiphilic block copolymer, which is synthesized through reversible addition-fragmentation chain transfer polymerization, are constructed. The NPs with fluorocarbon core and positively charged hydrophilic shells not only stabilize the sonosensitizer and improve its cellular uptake, but also act as an O2 carrier alleviating the hypoxic tumor environment. In vitro and in vivo experiments demonstrate that the NPs effectively deliver O2 to the tumor and supply sufficient O2 to Renca cells after ultrasound treatment. Consequently, the NPs inhibit hypoxia-induced resistance to SDT and significantly produce reactive oxygen species by activated porphyrin moieties, inducing apoptosis in cancer cells. These oxygen-enhanced sonosensitizer NPs hold promise for cancer therapies such as photodynamic therapy, radiotherapy, and chemotherapy by overcoming hypoxia-induced resistance.

A novel label-free impedance biosensor for KRAS G12C mutations detection based on PET-RAFT and ROP synergistic signal amplification

The KRAS G12C mutations, as crucial biomarkers, are closely associated with non-small cell lung cancer. Here, a novel label-free electrochemical biosensor with synergistic signal amplification of photocell energy transfer-reversible addition fragmentation chain transfer (PET-RAFT) and ring-opening polymerization (ROP) was developed for the first time for sensitive detection of KRAS G12C mutations. Specifically, hairpin DNA (hDNA), which act as biomolecular probe, was self-assembled on Au electrode surface by Au-S bond. 4-cyano-4-[(dodecylsulfanylthiocarbonyl) sulfanyl] pentanoic acid (CDTPA), the chain transfer agent of PET-RAFT reaction, was then attached to hDNA via amide bond. After that, the target DNA (tDNA) was captured on the electrode surface by complementary base pairing with hDNA. Subsequently, large numbers of electro-active monomers N-acryloxysuccinimide (NAS) were successfully grafted to the electrode surface via PET-RAFT reaction, which provided plenty of junction sites for doxorubicin-polycaprolactone (Dox-PCL) synthesized by ROP. Finally, the Dox-PCL was connected to the electrode surface by ester bond, significantly amplifying the electrochemical signal. Under optimized conditions, the biosensor has a wide linear detection range of 0.1 pM to 1 μM, with a detection limit of 86.9 fM. Attribute to its high sensitivity, specificity, reproducibility and stability, this biosensor possesses considerable potential in early diagnosis of disease and biomedical research.

From insects to mammals! Tissue accumulation and transgenerational transfer of micro/nano-plastics through the food chain

Despite extensive global attention on microplastic pollution, our understanding of the pathways underlying microplastic translocation, accumulation, and their potential impacts on ecosystems and human health through the food chain remains incomplete. To investigate the translocation and accumulation of microplastics from insects to mammals, we developed a novel oral exposure model that Tenebrio molitor larvae (yellow mealworms, invertebrate terrestrial insects) were firstly orally exposed to both micro and nanometer-sized plastics (M/NPs), and subsequently fed as a food source to mice (mammals). Our results provide clear evidence that micro/nanoplastics (M/NPs) do indeed translocate through the food chain, from lower to higher trophic levels. Fluorescence microscopy and tissue quantification revealed the accumulation of M/NPs in the digestive, somatic, and circulatory systems of the larvae. Specifically, the food chain transferred M/NPs were later detected in the digestive, respiratory, and urinary systems of mice, showcasing strong fluorescent signals in vital organs such as the lungs, liver, intestines, brain, and kidneys, as well as in embryos. These findings highlight the intricate dynamics of M/NPs contamination, emphasizing their ability to traverse biological barriers, accumulate in organisms, and potentially impact embryonic development via food chain transfer. Environmental ImplicationMicro/nano plastics (M/NPs) have emerged as a critical environmental hazard, with their ability to infiltrate food chains and accumulate in organisms posing serious risks. Despite rising awareness, the M/NPs translocation, bioaccumulation, and impacts on ecosystems and human health within food chains, remains poorly understood. In this study, we developed a novel model in which insects exposed to M/NPs are subsequently fed to mammals, revealing the transfer of M/NPs between species through the food chain. Our results demonstrate that the M/NPs penetrate biological barriers, accumulate in vital organs, and even reach embryos, raising serious concerns for environmental and human health.

Experimental and Simulation Study of Single-matrix, All-polymeric Thin-film Composite Membranes for CO2 Capture: Block vs Random Copolymers

High-performance, additive-free, all-polymeric thin-film composite (TFC) membranes were developed for CO₂ capture, focusing on a comparison between block and random copolymers (referred to as PTF) composed of hydrophobic poly(2,2,2-trifluoroethyl methacrylate) (PTFEMA) and CO2-philic polar poly(oxyethylene methacrylate) (POEM) chains. The PTF random copolymer, synthesized via free-radical polymerization (FRP), exhibited a disordered morphology. In contrast, the PTF block copolymer, synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization, formed a well-ordered hexagonally packed cylindrical structure, creating an amphiphilic, microphase-separated nanostructure. Molecular dynamics (MD) simulations revealed that in both copolymers, there was minimal interaction between the gases (CO₂ and N₂) and the hydrophobic PTFEMA segments, while CO₂ showed strong affinity for the hydrophilic POEM segments. The block and random copolymers demonstrated similar CO₂ permeance, which can be attributed to their comparable CO₂ diffusivity and solubility. However, the block copolymer exhibited significantly lower N₂ permeance than the random copolymer, resulting in nearly quadruple the CO₂/N₂ selectivity. This increase in selectivity was supported by the lower N₂ mean squared displacement (indicating reduced diffusivity) observed in the block copolymer. The PTF block copolymer outperformed the commercial Pebax block copolymer, achieving CO₂ capture efficiencies that surpass industrial standards for CO₂ separation and capture. This positions the single-matrix PTF block copolymer as a promising alternative to mixed-matrix membranes for practical applications in gas separation technologies.

Polyalkenamers as Drop-In Additives for Ring-Opening Metathesis Polymerization: A Promising Upcycling Paradigm.

We report a distinct strategy to upcycle waste polyalkenamers such as polybutadiene into new, performance-advantaged materials by using them as drop-in additives for ring-opening metathesis polymerization (ROMP). The polyalkenamers serve as competent chain-transfer agents in ROMPs of common classes of cyclic olefin monomers, facilitating good molecular weight control, allowing low Ru catalyst loadings, and enabling efficient incorporation of the polyalkenamer into the synthesized polymeric material. We successfully demonstrate ROMP using model polyalkenamers and translate these learnings to leverage commercial polybutadiene and acrylonitrile butadiene styrene (ABS) as chain transfer agents for ROMP copolymerizations. Critically, our strategy is shown to be highly efficient and operationally simple, quantitatively incorporating the polyalkenamer and inheriting aspects of its thermomechanical performance. Our results highlight a promising pathway for the upcycling of polyalkenamers and provide an alternative to existing deconstruction and functional upcycling strategies.

Catalyzing PET-RAFT Polymerizations Using Inherently Photoactive Zinc Myoglobin.

Protein photocatalysts provide a modular platform to access new reaction pathways and affect product outcomes, but their use in polymer synthesis is limited because co-catalysts and/or co-reductants are required to complete catalytic cycles. Herein, we report using zinc myoglobin (ZnMb), an inherently photoactive protein, to mediate photoinduced electron/energy transfer (PET) reversible addition-fragmentation chain transfer (RAFT) polymerizations. Using ZnMb as the sole reagent for catalysis, photomediated polymerizations of N,N-dimethylacrylamide in PBS were achieved with predictable molecular weights, dispersity values approaching 1.1, and high chain-end fidelity. We found that initial apparent rate constants of polymerization increased from 4.6×10-5 s-1 for zinc mesoporpyhrin IX (ZnMIX) to 6.5×10-5 s-1 when ZnMIX was incorporated into myoglobin to yield ZnMb, indicating that the protein binding site enhanced catalytic activity. Chain extension reactions comparing ZnMb-mediated RAFT polymerizations to thermally-initiated RAFT polymerizations showed minimal differences in block copolymer molecular weights and dispersities. This work enables studies to elucidate how protein modifications (e.g., secondary structure folding, site-directed mutagenesis, directed evolution) can be used to modulate polymerization outcomes (e.g., selective monomer additions towards sequence control, tacticity control, molar mass distributions).

Doping In Vivo Alkylation in E. coli by Introducing the Direct Sulfurylation Pathway of S. cerevisiae

AbstractMethylation and alkylation are important techniques used for the synthesis and derivatisation of small molecules and natural products. Application of S‐adenosylmethionine (SAM)‐dependent methyltransferases (MTs) in biotechnological hosts such as Escherichia coli lowers the environmental impact of alkylation compared to chemical synthesis and facilitates regio‐ and chemoselective alkyl chain transfer. Here, we address the limiting factor for SAM synthesis, methionine supply, to accelerate in vivo methylation activity. Introduction of the direct sulfurylation pathway, consisting of O‐acetylhomoserine sulfhydrolase (ScOAHS) and O‐acetyltransferase (ScMET2), from S. cerevisiae into E. coli and supplementation with methanethiol or the corresponding disulfide improves atom‐economic methylation activity in three different MT reactions. Up to 17‐fold increase of conversion compared to the sole expression of the MT and incorporation of up to 79 % of the thiol compound added were achieved. Promiscuity of ScOAHS allowed in vivo production of methionine analogues from organic thiols. Further co‐overproduction of a methionine adenosyltransferase yielded SAM analogues which were further transferred by MTs onto different substrates. For methylation of non‐physiological substrates, conversion rates up to 73 % were achieved, with an isolated yield of 41 % for N‐methyl‐2,5‐aminonitrophenol. The here described technique enables E. coli to become a biotechnological host for improved methylation and selective alkylation reactions.

Catalyzing PET‐RAFT Polymerizations Using Inherently Photoactive Zinc Myoglobin

AbstractProtein photocatalysts provide a modular platform to access new reaction pathways and affect product outcomes, but their use in polymer synthesis is limited because co‐catalysts and/or co‐reductants are required to complete catalytic cycles. Herein, we report using zinc myoglobin (ZnMb), an inherently photoactive protein, to mediate photoinduced electron/energy transfer (PET) reversible addition‐fragmentation chain transfer (RAFT) polymerizations. Using ZnMb as the sole reagent for catalysis, photomediated polymerizations of N,N‐dimethylacrylamide in PBS were achieved with predictable molecular weights, dispersity values approaching 1.1, and high chain‐end fidelity. We found that initial apparent rate constants of polymerization increased from 4.6×10–5 s−1 for zinc mesoporpyhrin IX (ZnMIX) to 6.5×10–5 s−1 when ZnMIX was incorporated into myoglobin to yield ZnMb, indicating that the protein binding site enhanced catalytic activity. Chain extension reactions comparing ZnMb‐mediated RAFT polymerizations to thermally‐initiated RAFT polymerizations showed minimal differences in block copolymer molecular weights and dispersities. This work enables studies to elucidate how protein modifications (e.g., secondary structure folding, site‐directed mutagenesis, directed evolution) can be used to modulate polymerization outcomes (e.g., selective monomer additions towards sequence control, tacticity control, molar mass distributions).

Influence of pH on the Self‐Assembly Properties of Heterofunctional POEGMA‐Based Block Copolymers During RAFT‐PISA

ABSTRACTPOEGMA‐based block copolymers self‐assemblies with surface‐functionalized carboxylic acid or propargyl groups were synthesized by successive reversible addition‐fragmentation chain transfer (RAFT) polymerization of oligo(ethylene glycol) methyl ether methacrylate (OEGMA) and RAFT‐mediated polymerization‐induced self‐assembly (RAFT‐PISA) in dispersion of 2‐(methacryloyloxy)‐N,N,N‐trimethylethanaminium hexafluorophosphate (METAPF6). The temperature responsive properties of the carboxylic acid–terminated POEGMA (POEGMACDP) and propargyl‐terminated POEGMA (POEGMACDPy) were studied in aqueous buffer solutions at pH 2.3 and 9.2. At pH 2.3, POEGMACDP aqueous solution exhibits a cloud point while no cloud point was observed at pH 9.2. POEGMACDPy shows a cloud point at both pH levels. The RAFT‐PISA in dispersion of METAPF6 at 75°C in either pH 2.3 or 9.2 buffer solution using POEGMACDP or POEGMACDPy as macro‐RAFT agents led to block copolymers, as confirmed by DOSY analysis. For POEGMACDP (DPn = 9), DPn,NMR,PMETAPF6 was 47 at pH 2.3 and 27 at pH 9.2 and for POEGMACDPy (DPn = 10), DPn,NMR,PMETAPF6 was 36 at pH 2.3 and 22 at pH 9.2, as shown by 1H NMR spectroscopy. Both in situ POEGMACDP‐b‐PMETAPF6 and POEGMACDPy‐b‐PMETAPF6 self‐assemblies in aqueous solutions exhibited an increase in Dh and PDI when the pH increased from 2.3 to 9.2, as measured by DLS at 20°C. TEM analyses revealed almost spherical self‐assemblies, unaffected by pH or chain‐end functionality.