Polymer Chain Ends Research Articles

End-Group Dye-Labeled Poly(hemiacetal ester) Block Copolymers: Enhancing Hydrolytic Stability and Loading Capacity for Micellar (Immuno-)Drug Delivery.

Polymers with hemiacetal esters integrated in their backbone provide beneficial degradation profiles for (immuno-) drug delivery. However, their fast hydrolysis and low drug loading capacity have limited their applications so far. Therefore, this study focuses on the stability and loading capacity of hemiacetal ester polymers. The hydrophobicity of the micellar core has a tremendous effect on the hemiacetal ester stability. For that purpose, we introduce a new monomer with a phenyl moiety for stabilizing the micellar core and improving drug loading. The carrier functionality can further be expanded by post-polymerization modifications via activated ester groups at the polymer chain end. This allows for covalent dye labeling, which provides substantial insights into the polymers' in vitro performance. Flow cytometric analyses on RAW dual macrophages revealed intact micelles exhibiting significantly higher cellular uptake compared to degraded species, thus, highlighting the potential of end group functionalized poly(hemiacetal ester)s for (immuno)drug delivery purposes.

‘Clickable’ polymer brush coated magnetic nanoparticles: Employing Diels-Alder and azide-alkyne cycloaddition for modular targeted drug delivery platforms

Effective methods of multi-functionalization of nanomaterials are essential for fabricating effective targeted drug delivery systems. Herein, we disclose the fabrication of polymer brush-coated magnetic nanoparticles that could be functionalized with drugs and targeting ligands through orthogonal click reactions. In particular, polymers containing electron-rich furan groups as functionalization handles are grown from the surface of magnetic nanoparticles using the ‘graft-from’ approach. Furthermore, azide groups are installed at the chain end of polymer brushes to furnish an orthogonally functionalizable system. The attachment of maleimide-containing fluorescent dyes and cytotoxic drugs using the Diels-Alder reaction is demonstrated. Drug-conjugated nanoparticles functionalized with integrin-targeting peptide using the azide-alkyne cycloaddition reaction undergo preferential uptake in cancer cells and show dose-dependent cytotoxicity. We envision that the modularly functionalizable system disclosed here could target various cancer cells using an appropriate combination of drugs and targeting groups.

Bacteria face trade-offs in the decomposition of complex biopolymers.

Although depolymerization of complex carbohydrates is a growth-limiting bottleneck for microbial decomposers, we still lack understanding about how the production of different types of extracellular enzymes affect individual microbes and in turn the performance of whole decomposer communities. In this work we use a theoretical model to evaluate the potential trade-offs faced by microorganisms in biopolymer decomposition which arise due to the varied biochemistry of different depolymerizing enzyme classes. We specifically consider two broad classes of depolymerizing extracellular enzymes, which are widespread across microbial taxa: exo-enzymes that cleave small units from the ends of polymer chains and endo-enzymes that act at random positions generating degradation products of varied sizes. Our results demonstrate a fundamental trade-off in the production of these enzymes, which is independent of system's complexity and which appears solely from the intrinsically different temporal depolymerization dynamics. As a consequence, specialists that produce either exo- or only endo-enzymes limit their growth to high or low substrate conditions, respectively. Conversely, generalists that produce both enzymes in an optimal ratio expand their niche and benefit from the synergy between the two enzymes. Finally, our results show that, in spatially-explicit environments, consortia composed of endo- and exo-specialists can only exist under oligotrophic conditions. In summary, our analysis demonstrates that the (evolutionary or ecological) selection of a depolymerization pathway will affect microbial fitness under low or high substrate conditions, with impacts on the ecological dynamics of microbial communities. It provides a possible explanation why many polysaccharide degraders in nature show the genetic potential to produce both of these enzyme classes.

Efficient Dienyl End‐Capping of Ruthenium Catalyzed Ring Opening Metathesis Polymerization with Allyl Compounds through Base‐Promoted Metallacyclobutane Decomposition

AbstractHerein we demonstrate an effective and facile end‐capping technique for ring‐opening metathesis polymerization (ROMP) using readily available allyl compounds as a new type of terminating agents. This new type of end‐capping reactions, which are based on the base‐promoted decomposition of ruthenocyclobutane intermediates, introduce diene moiety onto the chain end of ROMP polymers while simultaneously deactivating the ruthenium complex. These termination reactions are highly efficient, typically completing within 1 minute at 0 °C with >95 % end‐capping fidelity.

Efficient Dienyl End-Capping of Ruthenium Catalyzed Ring Opening Metathesis Polymerization with Allyl Compounds through Base-Promoted Metallacyclobutane Decomposition.

Herein we demonstrate an effective and facile end-capping technique for ring-opening metathesis polymerization (ROMP) using readily available allyl compounds as a new type of terminating agents. This new type of end-capping reactions, which are based on the base-promoted decomposition of ruthenocyclobutane intermediates, introduce diene moiety onto the chain end of ROMP polymers while simultaneously deactivating the ruthenium complex. These termination reactions are highly efficient, typically completing within 1 minute at 0 °C with >95 % end-capping fidelity.

Influence of the number of end-chain amine-functionalized arms of star-shaped functionalized SBR

Star-shaped SBRs with alkoxy silyl groups in the center of the molecule and amine groups at the polymer chain ends were prepared. The number of arms were varied, and its influence on the silica/silane-filled compound properties was investigated. The polymer–filler interactions and the filler–filler interactions were evaluated from the viscoelastic properties. The flocculation, tensile properties and tanδ at 60 °C, an indicator of rolling resistance, were investigated as well. The polymer–filler interactions were increased in the SBR with a higher number of arms due to the higher amount of amine groups in these SBRs. The Payne effect was slightly increased with a higher number of arms. This indicates a deteriorated micro-dispersion of the silica caused by too many interactions generated by the higher amount of amine groups in SBR. These high interactions due to the amine groups lead to higher tensile moduli. The combination of the higher polymer–filler interactions and the higher Payne effect in SBR with a high number of arms results in the same tanδ compared to the SBR with a low number of arms.

Two‐dimensional β‐ketoenamine linked azo covalent organic frameworks as heterogeneous catalysts for photo‐induced RCMP

AbstractPhoto‐induced reversible complexation‐mediated polymerization (RCMP) is a green and economical method to prepare polymers with precise molecular weights, narrow molecular weight distributions and functionally active chain ends. Covalent organic frameworks (COFs) are a promising heterogeneous photocatalyst for mediating RCMP due to their adjustable structure, band gap, and porosity. In this work, 1,3,5‐triformylphloroglucinol (Tp) and p‐azoaniline (Azo) were selected to construct 2D β‐ketoenamine linked Tp‐Azo‐COF as a heterogeneous photocatalyst to trigger RCMP under white light irradiation. A series of polymers with controllable molecular weight and narrow molecular weight distribution were successfully prepared by using Tp‐Azo‐COF as photocatalysis. On/off light experiments confirmed the good spatiotemporal control feature, and chain expansion experiments demonstrated the high “activity” of polymer chain ends. Furthermore, the mechanistic research elucidated that electron transfer between Tp‐Azo‐COF and initiator occurred, allowing the formation of reactive radicals to mediate RCMP. Density functional theory calculations revealed that the coordination of iodine on the initiator to catalyst obviously reduced the bond dissociation energy, leading to enhance in the polymerization rate. This work provides a platform for constructing heterogeneous photocatalysts with more efficient and stable to mediate RCMP.

Thermodynamically stable plumber's nightmare structures in block copolymers.

Block copolymer self-assembly affords diverse nanostructures, spanning from spheres and cylinders to networks, offering meticulous control over properties and functionalities at the nanoscale. However, creating thermodynamically stable network structures with high packing frustration remains a challenge. In this study, we report a methodology to access diverse network structures such as gyroid, diamond, and primitive phases from diblock copolymers using end group and linker chemistry. The stability of the medial packing of polymer chain ends (plumber's nightmare structure) over skeletal aggregation (gyroid) is attributed to the interplay between the strength of the end-end interactions and the initial shape of the curvature. Our study establishes an approach to develop tailored network structures from block copolymers, providing an important platform for using block copolymers in nanotechnology applications.

A one-pot approach towards polycarbonate-b-polyester block copolymers via chemoselective polymerization catalyzed by a one-component phosphonium borane Lewis pair

Chemoselective polymerization from a mixture of l-LA, CHO and CO2 enables the synthesis of PLLA, PCHC or PCHC-b-PLLA achieved by PBB-Br. The chemoselectivity depends on the nature of the growing polymer chain end.

Room temperature nickel‐catalyzed reductive coupling of end‐brominated polystyrene chains

AbstractFacile, room‐temperature coupling of brominated polymer chains can be accomplished in high yields (~80%) using a nickel‐based catalytic cycle that also includes magnesium and zinc. The extent of coupling (Xc) was found to be similarly high when performed under vacuum or with a nitrogen purge, although its effectiveness varied significantly as a function of the solvent, reagents, and the structure of the polymer chain end. Kinetic studies show that even at room temperature, nearly all coupling occurs within the first ~2 h of the reaction when performed under nitrogen or vacuum, with accompanying color changes occurring in the catalytic system coinciding with catalytic activity. One step of the mechanistic cycle is proposed to occur via chain‐end radical intermediates inserted into the catalytic cycle, consistent with the addition of a radical trap essentially thwarting the dimerization by capturing the polymer radical and preventing its inclusion in the reaction. The presence of aryl bromide functional groups, however, does not impede the coupling reaction, demonstrating the catalyst's preference for the chain‐end alkyl bromides under our conditions. The impact and necessity of the other components were also explored, supporting the importance of the MgCl2 serving as a Lewis acid to promote the reactivity of the CBr end groups.

Preparation and mechanical properties of fluoropolymer composite containing polyrotaxane and nanocellulose as organic fillers

AbstractPolymer‐based composites containing functional organic fillers with polyvinylidene fluoride (PVDF) as a matrix were prepared using a simple and short melt‐compounding method, and their mechanical properties were evaluated. Polyrotaxane and nanocellulose were used as functional organic fillers. A PVDF/organic filler composite with improved mechanical hardness was prepared, even when using a fluoropolymer that tends to separate phases from other components. The optimum conditions for improving in Young's modulus were estimated from the composites prepared by varying the organic filler content. As a result, the Young's modulus increased to 1548 MPa, maximum stress approached 50 MPa, and strain elongation was 20% at contents of polyrotaxane:nanocellulose = 0.6 wt%:0.3 wt%. Furthermore, the miscibility of both components was evaluated based on the change in the crystallization temperature of the composite, the PVDF matrix, and each organic filler. The partial miscibility and dispersion of the organic fillers in the fluoropolymer matrix are suggested to be responsible for improving the mechanical properties.Highlights Unique composites containing nanocellulose and polyrotaxane were prepared. Organic fillers were introduced into a phase‐separable fluoropolymer matrix. Mechanical properties were improved by introduction of organic fillers. Nanocellulose seems to adsorb to the polymer chain ends of fluoropolymer. Polyrotaxane showed partial miscibility with fluoropolymer matrix.

Temporal Regulation of PET-RAFT Controlled Radical Depolymerization.

A photocatalytic RAFT-controlled radical depolymerization method is introduced for precisely conferring temporal control under visible light irradiation. By regulating the deactivation of the depropagating chains and suppressing thermal initiation, an excellent temporal control was enabled, exemplified by several consecutive "on" and "off" cycles. Minimal, if any, depolymerization could be observed during the dark periods while the polymer chain-ends could be efficiently re-activated and continue to depropagate upon re-exposure to light. Notably, favoring deactivation resulted in the gradual unzipping of polymer chains and a stepwise decrease in molecular weight over time. This synthetic approach constitutes a simple methodology to modulate temporal control during the chemical recycling of RAFT-synthesized polymers while offering invaluable mechanistic insights.

Ring-opening polymerization of cyclic oligosiloxanes without producing cyclic oligomers.

A long-standing problem associated with silicone synthesis is contamination of the polymer products with 10 to 15% cyclic oligosiloxanes that results from backbiting reactions at the polymer chain ends. This process, in competition with chain propagation through ring-opening polymerization (ROP) of cyclic monomers, was thought to be unavoidable and routinely leads to a thermodynamically controlled reaction mixture (polymer/cyclic oligosiloxanes = 85/15). Here, we report that simple alcohol coordination to the anionic chain ends prevents the backbiting process and that a well-designed phosphonium cation acts as a self-quenching system in response to loss of coordinating alcohols to stop the reaction before the backbiting process begins. The combination of both effects allows a thermodynamically controlled ROP of the eight-membered siloxane ring D4 without producing undesirable cyclic oligosiloxanes.

CO2-Responsive drug delivery system created by supramolecular design and assembly for safer, more effective cancer therapy

We developed a carbon dioxide (CO2)-responsive supramolecular drug carrier system through a combination of hydrophobic CO2-sensitive imidazole-containing rhodamine 6G (I–R6G) as an efficient anticancer agent and hydrophilic ureido-cytosine (UrCy) end-capped polyethylene glycol (UrCy-PEG) as a self-assembled nanocarrier that could potentially enhance the safety and efficiency of cancer treatment. Owing to the self-complementary quadruple hydrogen bonding interactions between the UrCy moieties at the polymer chain ends, UrCy-PEG can spontaneously self-assemble into spherical-like nanoobjects in water that can effectively encapsulate hydrophobic I–R6G and form co-assembled nanoparticles with tunable sizes (depending on the I–R6G loading content). These nanoparticles display several notable physical features, including high structural stability in normal physiological aqueous media or red blood cell-containing media, unique CO2-responsiveness, and controlled CO2-sensitive I–R6G release. In vitro cytotoxicity assays clearly indicated I–R6G-loaded nanoparticles exerted selective cytotoxicity towards cancer cells, but had no adverse effects on normal cells. I–R6G-loaded nanoparticles exerted significantly higher levels of cytotoxicity at lower doses in CO2-treated cell culture media compared to I–R6G-loaded nanoparticles in pristine media. More importantly, cellular assays demonstrated that—in comparison to I–R6G-loaded nanoparticles in pristine media—CO2-treated culture media accelerated macropinocytic internalization of I–R6G-loaded nanoparticles into cancer cells, and subsequently led to more rapid induction of apoptosis in cancer cells and massive programmed cell death. Thus, this newly created system may act as a potential route to manipulate the drug delivery and release performance of self-assembled nanobjects for efficient cancer therapy.

Novel Chain-End Modification of Polymer Iodides via Reversible Complexation-Mediated Polymerization with Functionalized Radical Generation Agents.

The modification of polymer chain ends is important in order to produce highly functional polymers. A novel chain-end modification of polymer iodides (Polymer-I) via reversible complexation-mediated polymerization (RCMP) with different functionalized radical generation agents, such as azo compounds and organic peroxides, was developed. This reaction was comprehensively studied for three different polymers, i.e., poly (methyl methacrylate), polystyrene and poly (n-butyl acrylate) (PBA), two different functional azo compounds with aliphatic alkyl and carboxy groups, three different functional diacyl peroxides with aliphatic alkyl, aromatic, and carboxy groups, and one peroxydicarbonate with an aliphatic alkyl group. The reaction mechanism was probed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The combination of PBA-I, iodine abstraction catalyst and different functional diacyl peroxides enabled higher chain-end modification to desired moieties from the diacyl peroxide. The dominant key factors for efficiency in this chain-end modification mechanism were the combination rate constant and the amount of radicals generated per unit of time.

Hybrid of Organophotoredox- and Cu-Mediated Pathways Enables Atom Transfer Radical Polymerization with Extremely Low Catalyst Loading

The rise of photoredox catalysis has extended the landscape of reversible-deactivation radical polymerization. Recently, visible-light-driven photoredox/Cu dual catalyzed atom transfer radical polymerization (photoATRP) has become an emerging trend, providing well-defined polymer under low copper catalyst loading. In this work, we described a dual catalyzed ATRP using CuBr2/tris(2-pyridinylmethyl)amine (TPMA) and donor–acceptor-type organophotoredox catalysts (OPCs) with visible light absorption. The excited state OPC can reduce both dormant polymer chain-end and CuBr2/TPMA, generating propagating radical species and CuBr/TPMA, respectively. This indicates that the mechanism is a hybrid of organophotoredox-mediated and Cu-mediated ATRP. The photoATRP driven by 425 nm light irradiation produced a series of well-defined polymethacrylates under extremely low catalyst loadings (5 or 10 ppm CuBr2 and 1 ppm OPC relative to monomer). The method also showed excellent temporal control over polymerization and oxygen tolerance.

Experimental and theoretical insights into cationic polymerization of para-N,N-dimethylaminostyrene

The cationic polymerization electron-rich para-N,N-dimethylaminostyrene (DMAS) for high-molecular-weight polymer is few and highly challenging because of the ease reaction of N,N-dimethylamino group with proton or carbocation. In this contribution, three kinds of initiating systems including Lewis’s acid (BF3•OEt2), Brønsted acid (CF3SO3H, TfOH), and the carbocation system (IBVE-HCl/SnCl4, IBVE: isobutyl vinyl ether) were used in DMAS polymerization·BF3•OEt2 showed the highest efficiency for DMAS polymerization to afford high-molecular-weight poly(para-N,N-dimethylaminostyrene) (PDMAS). Copolymerizations of DMAS and 4-methoxystyrene (MOS) were unsuccessful no matter what the monomer feeding mode was, which only produced PDMAS or the blends of two homopolymers. Polymer chain-end analysis and NMR analysis of the intermediate showed that DMAS polymerizations obeyed cationic chain polymerization mechanism. Comprehensive theoretical DFT studies were performed to gain insight into the polymerization mechanism of DMAS. The chain transfer to the dimethylamino group of DMAS monomer was clearly found to be unique and curial to unexpected DMAS polymerization behavior.

Dual Thermo- and pH-Responsive Block Copolymer of Poly(N-isopropylacrylamide)-block-Poly(N,N-diethylamino Ethyl Acrylamide): Synthesis, Characterization, Phase Transition, and Self-Assembly Behavior in Aqueous Solution

Doubly thermo- and pH-responsive poly(N-isopropylacrylamide)-block-poly(N,N-diethylamino ethyl acrylamide) (PNIPAM-b-PDEAEAM) with different compositions were synthesized by reversible addition–fragmentation chain-transfer (RAFT) polymerization. The properties (solubility, self-assembly behavior) of these polymers and corresponding homopolymers in solution depend on the value of pH and the protonation degree of the diethylamino moiety. The effect of the nature of the polymer chain ends also appears to be critical to fully understand this behavior. At pH 10, both PNIPAM and PDEAEAM blocks are thermoresponsive and make a cooperative contribution to phase transition, and stable spherical nanoobjects are detected as temperature rises over transition point. At pH 4, PNIPAM-b-PDEAEAM with longer PDEAEAM length displays a two-step thermoresponsive behavior; upon heating, PNIPAM chains undergo shrinkage and subsequent reorganization causing the formation of large aggregates with a positively charged shell made of PDEAEAM block in its protonated state. The aggregation processes are also particularly sensitive to kinetic considerations, and therefore, measured size of aggregates depends strongly on the history of polymer solution.

Efficient Self-Immolative RAFT End Group Modification for Macromolecular Immunodrug Delivery.

The reversible addition-fragmentation chain-transfer (RAFT) polymerization provides access to a broad variety of biocompatible and functional macromolecules for diverse polymer-drug conjugates. Due to thiocarbonylthio groups at the ends of each growing polymer chain, they can straightforwardly be converted into disufilde-containing self-immolative motives for reversible drug conjugation by traceless linkers. This may be relevant for RAFT-polymerized poly(N,N-dimethylacrylamide) (pDMA), which has been demonstrated to provide similar properties as poly(ethylene glycol) (PEG) in terms of improving the drug's poor pharmacokinetic profile or enhancing its bioavailability. For that purpose, we established a highly efficient one-pot reaction procedure for introducing various functionalities including both primary and secondary amines and primary alcohols and demonstrated their reversible conjugation and traceless release from pDMA's polymer chain end. Next, a first polymer-drug conjugate with a Toll-like receptor agonist exhibited significantly increased activity in vitro compared to conventional irreversibly covalently fixed variants. Finally, α-ω-bifunctional dye or drug conjugates could be generated by a cholesterol-modified RAFT chain-transfer agent. It facilitated the polymer-drug conjugate's internalization at the cellular level monitored by flow cytometry and confocal imaging. This approach provides the basis for a variety of potentially impactful polymer-drug conjugates by combining versatile small molecular drugs with a plethora of available RAFT polymers through reductive-responsive self-immolative linkers.

Cast, Dip, Spray, and Print─Covalently Embedded Photochromic Materials from a Versatile Spiropyran Conjugate

Dynamic photochromic dyes are in great demand for various applications. These are used as active materials with tunable optical properties. However, producing photochromic materials in significant quantities is still a challenge. The ability to retain and prolong the interconversion of switching between open and closed forms is affected by undesirable aggregation of dyes in the matrix. The often-employed method of adding photochromic dyes into bulk materials causes issues such as aggregation, leaching of dye, and photoinstability. A versatile light-responsive spiropyran substituted azo-initiator was conveniently synthesized and utilized for incorporating photochromic units at the α-chain end of the vinyl polymers. Accordingly, processes in bulk, solution, and emulsion/dispersion were developed by radical polymerization of common vinyl monomers such as styrene and acrylates. This approach enabled the preparation of light-responsive polymers possessing photochromic spiropyran units covalently incorporated at the polymer chain end. Thus, monodisperse, covalently embedded photochromic colloidal particles with low dye content (<0.1 mmol) were prepared. The fabrication and high-resolution spatiotemporal control of materials such as gels, elastomers, resins, and transparent films of commodity polymers embedded with photochromic units are demonstrated with detailed coloring, fading, and fatigue behavior. The facile and straightforward approach developed to prepare photochromic colloidal particles can be applied to any substrate through cast, dip, spray, or print to make “smart” photochromic materials.