Supramolecular Diblock Copolymers Research Articles

Catalytic effect of microflow space for supramolecular block co-polymerization of water-soluble porphyrins.

Using microflow space, a catalytic effect was achieved for supramolecular polymerization. With increasing reactivity at the polymer end, the selective connection of active monomers formed new block domains, avoiding fast homo-assembly. Binding of less-reactive monomers at the polymer end overcame steric bulkiness, affording a stable supramolecular diblock copolymer (SdiBCP).

Cover Feature: Automated Supramolecular Polymerization in a Microflow: A Versatile Platform for Multistep Supramolecular Reactions (ChemPlusChem 3/2023)

The cover feature image shows three-stream flows generated in microflow channels, which provide versatile reaction fields for automated supramolecular polymerization, realizing multiple operations: the injection of monomers, selective reactions, recovery of monomers, and purification of supramolecular polymers. The reaction occurred selectively at the forward-facing terminus of the supramolecular polymer, leading to a high-purity supramolecular diblock copolymer. More information can be found in the Research Article by Kae Yamashita and Munenori Numata.

Automated Supramolecular Polymerization in a Microflow: A Versatile Platform for Multistep Supramolecular Reactions.

This work reports a basic microflow system capable of performing multistep supramolecular polymerization. In this system, injection of the monomer, directional supramolecular copolymerization, removal of the unreacted monomer, and purification of the product supramolecular diblock copolymers are realized along a three-stream flow. When injecting a supramolecular polymer into the central stream of the three-stream flow, the supramolecular polymerization always occurs in the central flow, with the two lateral flows serving as supply and removal lines for the monomer. Employing two kinds of perylene bisimide derivatives as monomers, we confirmed that the reaction occurred selectively at the forward-facing terminus of the supramolecular polymer, along with recovery of the unreacted monomer, ultimately leading to a high-purity supramolecular diblock copolymer. Diblock copolymers are basic units for preparing multicomponent supramolecular block copolymers. Thus, connecting the present system in series would, in principle, result in a "microplant" capable of producing supramolecular polymers having desired inner complexity.

Competitive hydrogen bonding induced phase separation in supramolecular comb-shaped diblock copolymer

In this study, a route to prepare nanostructure in miscible diblock copolymers by utilization of competitively intermolecular hydrogen-bonding interactions is demonstrated. Block copolymers poly(4-vinylpyridine-b-4-hydroxybutyl acrylate) (P4VP-b-P4HBA) with various block ratios were synthesized and they were demonstrated to be miscible due to the intramolecular hydrogen bonding. By combination of P4VP-b-P4HBA and 3-pentadecylphenol (PDP), the miscible block copolymer forms comb-shaped di-block copolymer complexes through the competition interactions between the hydroxyl groups of PDP (proton donors) and the nitrogen of the pyridine rings of the P4VP blocks (proton acceptors). Upon blending with PDP, we observed morphology change from sphere structure to cylindrical, and lamellar, in a manner strongly dependent on the P4HBA fraction. The microstructure of this special comb-shaped di-block copolymer shows a strong sensitivity to the temperature. The results from the in situ small angle X-ray scattering experiments have demonstrated that, even below the order-disorder temperature, the size of the phase domain decreases with increasing temperature due to decrease of the strength of the hydrogen bond upon heating.

ROMP of supramolecular norbornene monomers containing β-cyclodextrin–ferrocene (/adamantane) inclusion complexes

Through the use of N-[2′-ferrocenylformamido-ethyl]-cis-5-norbornene-exo-2,3-dicarboximide (NFc) and N-[2′-adamantylformamido-ethyl]-cis-5-norbornene-exo-2,3-dicarboximide (NAd), we report the fabrication of two novel supramolecular norbornene monomers, NFc@β-CD and NAd@β-CD, through β-cyclodextrin (β-CD)/ferrrocene(Fc)- and β-CD/adamantane (Ad)-based host–guest complexation. The formation and structure of the two monomers were verified by various techniques, such as 1H and 13C NMR, 2D NOESY, IR and UV–vis spectroscopic methods. The ROMP (ring-opening metathesis polymerization) feasibility of the two supramolecular monomers was further confirmed by the successful preparation of two homopolymers (P(NFc@β-CD) and P(NAd@β-CD)) and two diblock copolymers (PNFc-b-P(NAd@β-CD) and P(NFc@β-CD)-b-P(NAd@β-CD)). The prepared polymers were adequately analyzed using 1H and 13C NMR, IR, UV–vis, end-group analysis and GPC methods. Based on the obtained results, we believe that (1) both supramolecular monomers exhibited “living” and “controlled” ROMP reactions; (2) the β-CD/Fc and β-CD/Ad inclusion complexes were not disassembled during the ROMP reactions of the two supramolecular monomers; and (3) the functional groups of β-CD had a negligible effect on the catalytic activity of the third-generation Grubbs’ catalyst. In short, this work indicated that the direct ROMP of β-CD-containing supramolecular monomers was a feasible route for preparing supramolecular polynorbornene-based homopolymers and copolymers, and this route is expected to have great potential for the preparation of various supramolecular polynorbornenes and functional materials. Two novel supramolecular norbornene monomers were prepared according to β-cyclodextrin–ferrocene (/adamantane) host–guest interactions and exhibited both the “living” and “controlled” ROMP characteristics with the aid of the third-generation Grubbs’ catalyst for the construction of corresponding supramolecular homopolymers and diblock copolymers.

Simulation Study of Process-Controlled Supramolecular Block Copolymer Phase Separation with Reversible Reaction Algorithm.

A supramolecular diblock copolymer formed by reversible bonds between the two blocks shows a rich microphase separation behavior and has great application potential in stimuli-responsive materials. We propose a novel method to describe supramolecular reactions in dissipative particle dynamics, which includes a reversible reaction to accurately reproduce the strength, saturation, and dynamic properties of the reversible bonds in the simulations. The thermodynamic properties and dynamic processes of the supramolecular diblock copolymer melts in both equilibrium and non-equilibrium states were studied using this method. The simulation results show that the method can faithfully characterize phase behaviors and dynamic properties of supramolecular diblock copolymer melts, especially in a non-equilibrium state, which provides a novel tool to unveil self-assembly mechanism and describe the properties of supramolecular block copolymers.

Fabrication of a Dual-Stimuli-Responsive Supramolecular Micelle from a Pillar[5]arene-Based Supramolecular Diblock Copolymer for Photodynamic Therapy.

A pH and thermo dual-responsive supramolecular diblock copolymer is constructed by host-guest recognition of pillar[5]arene and viologen salt. The host polymer, poly(N,N-dimethylaminoethyl methacrylate) bearing pillar[5]arene as the terminal group (P[5]A-PDMAEMA) is synthesized by atom transfer radical polymerization (ATRP). Guest polymer, ethyl viologen-ended poly(N-isopropylacrylamide) (EV-PNIPAM) is prepared by reversible addition-fragmentation chain transfer polymerization. The supramolecular diblock copolymer can be self-assembled into stable supramolecular nanoparticles in aqueous solution at 40 °C, which show excellent pH and thermo responsiveness. The nanoparticles are further applied in the encapsulation of photosensitizers (pyropheophorbide-a, PhA) for photodynamic therapy (PDT). The dual-responsive nanoparticles can efficiently release PhA in acidic environment at 25 °C. Based on the result of cell experiments, PhA-loaded nanomicelles exhibit excellent PDT efficacy and low dark toxicity toward A549 cells. Thus, this supramolecular diblock copolymer enriches the methodology of constructing stimuli-responsive drug carriers and presents a great potential in PDT.

Micelles Protect Intact Metallo-supramolecular Block Copolymer Complexes from Solution to Gas Phase during Electrospray Ionization

Supramolecular diblock copolymers using metal-ligand coordination can be synthesized under ambient conditions by delicate design of the end groups of the homopolymer chains. However, mass spectrometric analysis of such metallo-supramolecular copolymers is challenging. One of the reasons is the nonpolarity of the polymer chains, making it hard to disperse the complexes in electrospray ionization (ESI)-friendly environments. The other difficulty is the noncovalent nature of such copolymers, which is easily disrupted during the ionization. Here, we demonstrate that the intact metallo-supramolecular diblock copolymers can be maintained sufficiently during the ESI process in aqueous solution within micelles. The high-resolution mass spectrometric evidence revealed that the surfactant molecules effectively protect the noncovalent binding of the complexes into gaseous ions. Intriguingly, surfactant molecules were sufficiently detached away from the copolymer complexes, giving unambiguous mass spectra that were predominated by intact diblock copolymers. This ESI-based approach allowed us to investigate the relative bond strengths of metal-to-ligand complexation using collision-induced dissociation (CID) in the ion trap mass spectrometry. Conformational features and collision cross sections of the copolymers were thus obtained using subsequent ion mobility spectrometry mass spectrometry (IMS-MS). Remarkable environment-dependent conformations of the denoted diblock copolymers were found using this mass spectrometric platform.

The Origin of Hierarchical Structure Formation in Highly Grafted Symmetric Supramolecular Double-Comb Diblock Copolymers.

Involving supramolecular chemistry in self-assembling block copolymer systems enables design of complex macromolecular architectures that, in turn, could lead to complex phase behavior. It is an elegant route, as complicated and sensitive synthesis techniques can be avoided. Highly grafted double-comb diblock copolymers based on symmetric double hydrogen bond accepting poly(4-vinylpyridine)-block-poly(N-acryloylpiperidine) diblock copolymers and donating 3-nonadecylphenol amphiphiles are realized and studied systematically by changing the molecular weight of the copolymer. Double perpendicular lamellae-in-lamellae are formed in all complexes, independent of the copolymer molecular weight. Temperature-resolved measurements demonstrate that the supramolecular nature and ability to crystallize are responsible for the formation of such multiblock-like structures. Because of these driving forces and severe plasticization of the complexes in the liquid crystalline state, this supramolecular approach can be useful for steering self-assembly of both low- and high-molecular-weight block copolymer systems.

Asymmetric supramolecular double-comb diblock copolymers: From plasticization, to confined crystallization, to breakout

The combination of asymmetric P4VP-b-PAPI diblock copolymers (i.e. fP4VP≠fPAPI) and 3-NDP surfactants in hydrogen-bonded [poly(4-vinylpyridine)-block-poly(N-acryloylpiperidine)](3-nonadecylphenol)x (P4PA(3-NDP)x) supramolecular double-comb diblock copolymers could potentially result in rather interesting morphologies. However, plasticization of the copolymer and the ability of 3-NDP to crystallize were found to affect their self-assembly significantly. In general, for high comb densities x, the complex's tendency to crystallize and its preference to form a flat interface dominated microphase separation. Lower values of x on the other hand gave uneven distribution of 3-NDP, resulting in a higher glass transition temperature of the P4VP block. Crystallization of 3-NDP's aliphatic tails was therefore in most cases restricted to the preferential PAPI microdomains, thereby maintaining the large length scale block copolymer morphology that was already present in the melt. Such behavior is identical to self-assembly of linear semicrystalline diblock copolymers, as in these type of systems structure formation depends on the segregation strength and relative magnitude of the order-disorder transition (TODT), Tg and Tc, leading to mechanisms like confined crystallization or breakout.

A Multiresponsive Amphiphilic Supramolecular Diblock Copolymer Based on Pillar[10]arene/Paraquat Complexation for Rate-Tunable Controlled Release.

Herein, for rate-tunable controlled release, the authors report a new facile method to prepare multiresponsive amphiphilic supramolecular diblock copolymers via the cooperative complexation between a water-soluble pillar[10]arene and paraquat-containing polymers in water. This supramolecular diblock copolymer can self-assemble into multiresponsive polymeric micelles at room temperature in water. The resultant micelles can be further used in the controlled release of small molecules with tunable release rates depending on the type of single stimulus and the combination of various stimuli.

Thermo- and oxidation-responsive supramolecular vesicles constructed from self-assembled pillar[6]arene-ferrocene based amphiphilic supramolecular diblock copolymers

Thermo- and oxidation-responsive pillar[6]arene-ferrocene based supramolecular vesicles were constructed for controlled drug release.

Supramolecular Diblock Copolymers Featuring Well-defined Telechelic Building Blocks.

We report supramolecular AB diblock copolymers comprised of well-defined telechelic building blocks. Helical motifs, formed via reversible addition-fragmentation chain-transfer (RAFT) or anionic polymerization, are assembled with coil-forming and sheet-featuring blocks obtained via atom-transfer radical polymerization (ATRP) or ring-opening metathesis polymerization (ROMP). Interpolymer hydrogen bonding or metal-coordination achieves dynamic diblock architectures featuring hybrid topologies of coils, helices, and/or π-stacked sheets that, on a basic level, mimic protein structural motifs in fully synthetic systems. The intrinsic properties of each block (e.g., circular dichroism and fluorescence) remain unaffected in the wake of self-assembly. This strategy to develop complex synthetic polymer scaffolds from functional building blocks is significant in a field striving to produce architectures reminiscent of biosynthesis, yet fully synthetic in nature. This is the first plug-and-play approach to fabricate hybrid π-sheet/helix, π-sheet/coil, and helix/coil architectures via directional self-assembly.

Supramolecular Diblock Copolymers Featuring Well‐defined Telechelic Building Blocks

AbstractWe report supramolecular AB diblock copolymers comprised of well‐defined telechelic building blocks. Helical motifs, formed via reversible addition‐fragmentation chain‐transfer (RAFT) or anionic polymerization, are assembled with coil‐forming and sheet‐featuring blocks obtained via atom‐transfer radical polymerization (ATRP) or ring‐opening metathesis polymerization (ROMP). Interpolymer hydrogen bonding or metal‐coordination achieves dynamic diblock architectures featuring hybrid topologies of coils, helices, and/or π‐stacked sheets that, on a basic level, mimic protein structural motifs in fully synthetic systems. The intrinsic properties of each block (e.g., circular dichroism and fluorescence) remain unaffected in the wake of self‐assembly. This strategy to develop complex synthetic polymer scaffolds from functional building blocks is significant in a field striving to produce architectures reminiscent of biosynthesis, yet fully synthetic in nature. This is the first plug‐and‐play approach to fabricate hybrid π‐sheet/helix, π‐sheet/coil, and helix/coil architectures via directional self‐assembly.

Synthesis and characterization of thermo-responsive supramolecular diblock copolymers

In this paper, we report the synthesis and characterization of a new thermo-responsive supramolecular amphiphiles diblock copolymer, methoxy poly (ethylene glycol)-block-Poly(N-isopropylacrylamide) (mPEG-b-PNIPAM). The mPEG with β-cyclodextrin (β-CD) group and the PNIPAM with adamantine (AD) group were synthesized, respectively, and mPEG-b-PNIPAM was then obtained by the host-guest inclusion between AD and β-CD. The structure and molecular weight of mPEG-b-PNIPAM was confirmed by 1H NMR and GPC measurements. At low temperature (T < 33 °C), the PNIPAM block is hydrophilic. With increasing temperature, the hydrophobicity the of PNIPAM block increases. This molecular feature leads to interesting aggregation behavior of micelles in aqueous solutions at different temperatures. The self-assembly was revealed by UV, DLS measurements, and TEM observations.

Poly(lactic acid)/poly(ethylene glycol) supramolecular diblock copolymers based on three-fold complementary hydrogen bonds: Synthesis, micellization, and stimuli responsivity

Thymine-terminated poly(lactic acid) (PLA-THY) and diaminotriazine-terminated poly(ethylene glycol) (PEG-DAT) are synthesized and they can form the supramolecular amphiphilic diblock copolymers in solution through the thymine/diaminotriazine complementary hydrogen bonding interactions. Such supramolecular copolymers self-assemble into the stimuli-responsive micelles in aqueous solution. Micelle size, crystalline state, stimuli responsibility, drug loading and release behavior of the supramolecular micelles can be readily tuned from the block length, stereostructure, homo and stereocomplex crystallizations of hydrophobic PLA blocks. The enantiomerically-mixed supramolecular copolymers with both poly(l-lactic acid) (PLLA) and poly(d-lactic acid) (PDLA) blocks assemble into the stereocomplexed micelles, while those having the isotactic PLLA (or PDLA) and atactic poly(d,l-lactic acid) (PDLLA) blocks form the homocrystalline and amorphous micelles, respectively. The stereocomplexed and amorphous micelles exhibit smaller size than their homocrystalline analogs, all of which are much larger than the micelles formed from the conventional covalently-bonded diblock copolymers. The supramolecular micelles are sensitive to the external stimuli such as pH and ion. The homocrystalline and stereocomplexed micelles undergo fast aggregation in the acidic and salted solutions due to the disassociation of complementary hydrogen bonds. The stereocomplexed micelles exhibit larger drug loading content and slower drug release rate than the amorphous and homocrystalline ones, because of the larger polymer/drug interactions and tighter chain packing inside the micelle cores.

Orthogonal Approach to Construct Cell-Like Vesicles via Pillar[5]arene-Based Amphiphilic Supramolecular Polymers

A reduction-responsive supramolecular diblock copolymer was successfully constructed by the orthogonal assembly of two homopolymers in aqueous solution via pillar[5]arene-based host–guest interactions for the first time. The homopolymers, namely, polystyrene modified with ethyl viologen as the terminal group (PS-EV) and polyethylene glycol bearing pillar[5]arene (PEG-P[5]A), were synthesized via reversible addition–fragmentation chain transfer (RAFT) polymerization and coupling reaction, respectively. The supramolecular diblock copolymer can self-assemble into stable binary cell-like vesicles in aqueous solution, where a spherical micelle as the cell nucleus was embedded in a clear outer vesicle as the cell membrane. The cell-like vesicles can be disassembled into spherical aggregates through addition of reducing agent and further used for encapsulation and controlled release of model molecules.

Highly Ordered Nanoporous Films from Supramolecular Diblock Copolymers with Hydrogen‐Bonding Junctions

AbstractWe designed efficient precursors that combine complementary associative groups with exceptional binding affinities and thiocarbonylthio moieties enabling precise RAFT polymerization. Well defined PS and PMMA supramolecular polymers with molecular weights up to 30 kg mol−1 are synthesized and shown to form highly stable supramolecular diblock copolymers (BCPs) when mixed, in non‐polar solvents or in the bulk. Hierarchical self‐assembly of such supramolecular BCPs by thermal annealing affords morphologies with excellent lateral order, comparable to features expected from covalent diblock copolymer analogues. Simple washing of the resulting materials with protic solvents disrupts the supramolecular association and selectively dissolves one polymer, affording a straightforward process for preparing well‐ordered nanoporous materials without resorting to crosslinking or invasive chemical degradations.

Highly ordered nanoporous films from supramolecular diblock copolymers with hydrogen-bonding junctions.

We designed efficient precursors that combine complementary associative groups with exceptional binding affinities and thiocarbonylthio moieties enabling precise RAFT polymerization. Well defined PS and PMMA supramolecular polymers with molecular weights up to 30 kg mol(-1) are synthesized and shown to form highly stable supramolecular diblock copolymers (BCPs) when mixed, in non-polar solvents or in the bulk. Hierarchical self-assembly of such supramolecular BCPs by thermal annealing affords morphologies with excellent lateral order, comparable to features expected from covalent diblock copolymer analogues. Simple washing of the resulting materials with protic solvents disrupts the supramolecular association and selectively dissolves one polymer, affording a straightforward process for preparing well-ordered nanoporous materials without resorting to crosslinking or invasive chemical degradations.

Photochemical Design of Stimuli-Responsive Nanoparticles Prepared by Supramolecular Host–Guest Chemistry

We introduce the design of a thermoresponsive nanoparticle via sacrificial micelle formation based on supramolecular host–guest chemistry. Reversible addition–fragmentation chain transfer (RAFT) polymerization was employed to synthesize well-defined polymer blocks of poly(N,N-dimethylacrylamide) (poly(DMAAm)) (Mn,SEC = 10 700 g mol–1, Đ = 1.3) and poly(N-isopropylacrylamide) (poly(NiPAAm)) (Mn,SEC = 39 700 g mol–1, Đ = 1.2), carrying supramolecular recognition units at the chain termini. Further, 2-methoxy-6-methylbenzaldehyde moieties (photoenols, PE) were statistically incorporated into the backbone of the poly(NiPAAm) block as photoactive cross-linking units. Host–guest interactions of adamantane (Ada) (at the terminus of the poly(NiPAAm/PE) chain) and β-cyclodextrin (CD) (attached to the poly(DMAAm chain end) result in a supramolecular diblock copolymer. In aqueous solution, the diblock copolymer undergoes micellization when heated above the lower critical solution temperature (LCST) of the thermoresponsive poly(NiPAAm/PE) chain, forming the core of the micelle. Via the addition of a 4-arm maleimide cross-linker and irradiation with UV light, the micelle is cross-linked in its core via the photoinduced Diels–Alder reaction of maleimide and PE units. The adamantyl–cyclodextrin linkage is subsequently cleaved by the destruction of the β-CD, affording narrowly distributed thermoresponsive nanoparticles with a trigger temperature close to 30 °C. Polymer chain analysis was performed via size exclusion chromatography (SEC), nuclear magnetic resonance (NMR) spectroscopy, and dynamic light scattering (DLS). The size and thermoresponsive behavior of the micelles and nanoparticles were investigated via DLS as well as atomic force microscopy (AFM).