Synthesis and self-assembly of dendritic-linear block copolymers containing poly(mandelic acid) with discrete molecular weights and stereochemical structures.

In this work, we present the synthesis of uniform PMAs, where the number of repeat units and their stereochemical arrangement are precisely defined. Utilizing an iterative convergent approach with orthogonally protected dimandelic acid building blocks, we achieved high molecular weight PMAs with the desired number of repeat units, extending up to 144 mandelic acids. Additionally, stereochemically defined poly(l-mandelic acid)s with up to 32 repeat units were successfully synthesized. These uniform PMAs were subsequently coupled with uniform branched poly(ethylene glycol) blocks to create uniform dendritic-linear block copolymers. The self-assembly of these block copolymers in solution was systematically investigated. In solution self-assembly, the synthesized block copolymers showed multiple phases from cylinder to inverse cubic as the molecular weight of PMA increased. In the case of solvent diffusion-evaporation-mediated self-assembly, the block copolymers underwent a phase transition as the rate of water addition decreased.

Structural Homogeneity of Macromolecular Networks by End-to-End Click Chemistry between Discrete Tetrahedral Star Macromolecules.

Cross-linking via the end-to-end click chemistry of multiarm star polymers creates polymer networks with minimal inhomogeneities. Although it has been suggested that the mechanical and swelling properties of such networks depend on the absence of defects, the structural details of homogeneous networks created by this method have not yet been studied at the molecular level. Here, we report the synthesis of discrete tetrahedral star macromolecules (dTSMs) composed of polylactide (PLA) arms with discrete molecular weight and sequence. Polymer networks prepared by 4 × 4 cross-linking by Cu-free strain-promoted cyclooctyne-azide click chemistry (SPAAC) reaction exhibited a high degree of swelling (>40 fold by weight) in solvents without sacrificing mechanical robustness (elastic modulus >4 kPa). The structural details of the networks were investigated by network disassembly spectrometry (NDS) using MALDI-TOF mass spectrometry. By implementing a cleavable repeating unit in the discrete PLA arms of dTSM in a sequence-specific manner, the networks could be disassembled into fragments having discrete molecular weights precisely representing their connectivity in the network. This NDS analysis confirmed that end-to-end click reactions of dTSM networks resulted in the formation of a homogeneous network above the critical concentration (∼10 w/v%) of building blocks in the solution.

Monodisperse Cyclic Polymer Mechanochemistry: Scission Kinetics and the Dynamic Memory Effect with Ultrasonication and Ball-Mill Grinding.

A series of monodisperse cyclic and linear poly(d,l-lactide)s (c-PLA and l-PLA, respectively) were prepared with various degrees of polymerization (DP) using an iterative convergent synthesis approach. The absence of a molecular weight distribution provided us a chance to study their mechanochemical reactivity without obstructions arising from the size distribution. Additionally, we prepared l- and c-PLAs with identical DPs, which enabled us to attribute differences in scission rates to the cyclic polymer architecture alone. The polymers were subjected to ultrasonication (US) and ball-mill grinding (BMG), and their degradation kinetics were explored. Up to 9.0 times larger scission rates were observed for l-PLA (compared to c-PLA) with US, but the difference was less than 1.9 times with BMG. Fragmentation requires two backbone scission events for c-PLA, and we were able to observe linear intermediates (formed after a single scission) for the first time. We also developed a new method of studying the dynamic memory effect in US by characterizing and comparing the daughter fragment molecular weight distributions of l- and c-PLAs. These results provide new insights into the influence of the cyclic polymer architecture on mechanochemical reactions as well as differences in reactivity observed with US and BMG.

Semi-conductive micellar networks of all-conjugated diblock and triblock copolymer blends.

The crystallization-driven self-assembly of the blends of the all-conjugated block copolymers of poly(3-hexylthiophene) (P3HT) and poly(3-ethylhexylthiophene) (P3EHT) results in the cross-linking of the one-dimensional nanowires of P3HT-b-P3EHT, which is achieved by intercalating P3HT-b-P3EHT-b-P3HT into the nanowire cores. The micellar networks constitute flexible and porous materials that conduct electricity upon doping.

Nondestructive Sequencing of Enantiopure Oligoesters by Nuclear Magnetic Resonance Spectroscopy.

Sequence-defined synthetic oligomers and polymers are promising molecular media for permanently storing digital information. However, the information decoding process relies on degradative sequencing methods such as mass spectrometry, which consumes the information-storing polymers upon decoding. Here, we demonstrate the nondestructive decoding of sequence-defined oligomers of enantiopure α-hydroxy acids, oligo(l-mandelic-co-d-phenyl lactic acid)s (oMPs), and oligo(l-lactic-co-glycolic acid)s (oLGs) by 13C nuclear magnetic resonance spectroscopy. We were able to nondestructively decode a bitmap image (192 bits) encoded using a library of 12 equimolar mixtures of an 8-bit-storing oMP and oLG, synthesized through semiautomated flow chemistry in less than 1% of the reaction time required for the repetition of conventional batch reactions. Our results highlight the potential of bundles of sequence-defined oligomers as efficient media for encoding and decoding large-scale information based on the automation of their synthesis and nondestructive sequencing processes.

Effect of hydrophilic block end groups and block junction on block copolymer self-assembly in solution.

Recent research suggests that the end groups of polymers can affect their self-assembly. However, the effect of end groups on the self-assembly of block copolymers in solution remains unclear, and thus far, only micelle-vesicle transformations have been achieved via end-group modification. Herein, we report that hydrophilic block end groups and the junction between two blocks can affect the solution self-assembly of block copolymers, leading to the formation of different morphologies, including vesicles, cubosomes, and hexosomes. Poly(ethylene glycol)-b-polystyrene (PEG-b-PS) with hydroxyl, methoxy, azido, or amino groups at the PEG chain ends was synthesized and self-assembled in solution via the cosolvent method. As a result, the morphology of the block copolymers transformed from vesicles to hexosomes upon increasing the end-group hydrophobicity. In addition, a morphological transition from cubosomes to vesicles was observed upon changing the junction from a triazole to an amide, and the interaction between the solvent and end groups significantly affected the self-assembly behavior.

Templated synthesis of microparticles with carbonaceous skeletal structures using polymer cubosomes as templates.

Polymer cubosomes (PCs) are bicontinuous mesoporous colloidal particles that feature high surface areas and an extremely ordered crystalline pore network. PCs have attracted tremendous attention because of their potential applications in many fields. Herein, we obtained new microparticles with carbonaceous reticulated networks via templated synthesis using PCs as templates. The water-channel networks of the PCs were translated into a carbonaceous skeletal cubic structure. Carbon precursors were polymerized inside the water-channel networks of the PCs under acidic conditions without collapsing the internal crystalline mesophases. The carbonaceous interconnected networks created by the templated synthesis exhibited cubic crystalline skeletal networks similar to those of the PCs. These cubic-ordered mesoporous carbon (cOMC) microparticles exhibited several properties in electrochemical experiments. In addition, the nanoscopic structures and surfaces of these microparticles sustain electrochemically perturbing environments, and thus retain more than 90% capacitance after 1000 charge-discharge cycles.

Morphological Diversity from the Solution Self-Assembly of Block Copolymer Blends Containing High Molecular-Weight Hydrophobic Blocks.

Self-assembled structures of high molecular-weight block copolymers (BCPs) can prematurely settle to local energy minima without reaching a time-averaged equilibrium, resulting in the emergence of intriguing morphologies, such as 3D micellar networks. This nonergodic behavior is evident in binary blends of BCPs with different molecular weights. This study reports the solution self-assembly of the blends of two branched-linear BCPs with similar block chemistries but different molecular weights of the hydrophobic blocks. A progressive transition of morphologies from hexosomes and cubosomes to 3D micellar networks, short cylinders, and spherical micelles is demonstrated, which is driven by the increase in the composition of low-molecular-weight BCP in the blend. The labeling of the micellar networks using Au nanoparticles confirms that lower molecular-weight BCP concentrates at the surface of micellar networks.

Semiautomated synthesis of sequence-defined polymers for information storage.

Accelerated and parallel synthesis of sequence-defined polymers is an utmost challenge for realizing ultrahigh-density storage of digital information in molecular media. Here, we report step-economical synthesis of sequence-defined poly(l-lactic-co-glycolic acid)s (PLGAs) using continuous flow chemistry. A reactor performed the programmed coupling of the 2-bit storing building blocks to generate a library of their permutations in a single continuous flow, followed by their sequential convergences to a sequence-defined PLGA storing 64 bits in four successive flows. We demonstrate that a bitmap image (896 bits) can be encoded and decoded in 14 PLGAs using only a fraction of the time required for an equivalent synthesis by conventional batch processes. Accelerated synthesis of sequence-defined polymers could also contribute to macromolecular engineering with precision comparable to natural precedents.

Synthesis of cubic transition-metal networks from polymer cubosome templates.

The interfacial topology of block copolymer cubic mesophases opens only one of two internal water channel networks for diffusion. Utilizing this topology selection, single and double diamond cubic crystalline networks of Ni were synthesized from cubic block copolymer (BCP) mesophase templates via electroless plating, in which the lattice structures were converted to the polymer cubosome (PC) internal pore networks by selective metal-ion diffusion. This was accomplished by manipulating the BCP molecular weight, which consequently allowed for selective access to the PC internal pore networks. This work provides a selective protocol for highly defined transition-metal cubic networks that are suitable for application in catalysis, electrochemistry, and synthesis of metamaterials with photonic and magnetic properties.

Iterative Convergent Synthesis of Large Cyclic Polymers and Block Copolymers with Discrete Molecular Weights.

We report here the synthesis of cyclic polymers and block copolymers consisting of discrete numbers of repeating units without linear contaminants. The synthesis utilizes the intramolecular cyclization of end-functionalized poly(rac-lactide) (PLA) and its block copolymers with as many as 512 lactic acid units (37 kDa), synthesized by the iterative linear convergence of orthogonally protected building blocks. By exploiting the change in hydrodynamic volume upon cyclization of the linear polymers, macrocyclic polymers were isolated without linear precursors by preparative size-exclusion chromatography as a purification method. Our procedure also allowed the synthesis of a monodisperse cyclic block copolymer in a desired block ratio as a single compound (14 kDa).

Polymersome-Based Modular Nanoreactors with Size-Selective Transmembrane Permeability.

Polymersome nanoreactors encapsulating the enzymes or particulate catalysts attract interest because of their potential use as modular reactors to synthesize complex compounds via a cascade of chemical reactions in a single batch. To achieve these goals, a key requirement is the tunable permeability of the polymersome membrane, which allows the size-selective transportation of reagents and products while protecting the encapsulated catalysts during the chemical reaction. We report here a stimuli-responsive route for controlling the permeability of the polymersomes of the binary blend of poly(ethylene glycol)-b-polystyrene (PEG-b-PS) and poly(ethylene glycol)-b-poly(acrylbenzylborate) (PEG-b-PABB). The presence of H2O2 (1 mM) in the medium (0.1 M PBS, pH 7.4) triggers the oxidation of benzyl borate pendants of PABB to form poly(acrylic acid) (PAA). This transformation results in the perforation of the compartmentalizing membrane of polymersomes by the dissolution of PEG-b-PAA domains embedded in the inert PEG-b-PS matrix. By controlling the composition of the stimuli-responsive block copolymer, the polymersomes of the binary blend exhibit size-selective permeability without losing the structural integrity. Release of fluorescent guests with different sizes (fluorescein, PEG2k-Cm, PEG5k-Rho) can be controlled by tuning the composition (PEG-b-PS/PEG-b-PABB = 100/0-80/20) of blended polymersomes. Selective permeability of the membrane provides protection of the encapsulated enzymes from external proteases present in the medium, resulting in the one-pot synthesis of small molecules via cascades of chemical reactions. The nanoparticular catalysts are also encapsulated within the permeable polymersomes, serving as modular reactors for the conversion of organic compounds via a cascade of reactions.

Polymer Cubosomes: Infinite Cubic Mazes and Possibilities.

Block copolymers (BCPs) have been indispensable building blocks to create a range of soft nanostructures including discrete particulates (micelles and vesicles) and periodic structures via spontaneous assembly in bulk and in solution. The size, shape, and phase of these structures can be controlled by the rational design of the molecular structure of building blocks based on the structural analogy of BCPs to lipids and small molecule surfactants. Inverse bicontinuous cubic mesophases of polymers, or polymer cubosomes when in colloidal forms, are emerging nanostructures composed of triply periodic minimal surfaces (TPMSs) of block copolymer bilayers. Created by spontaneous assembly of BCPs in solution, polymer cubosomes internalize two nonintersecting nanochannel networks arranged in a cubic crystalline order. As well-defined porous particles with highly ordered internal structures and high surface-area-to-volume ratios, polymer cubosomes can be used for chemical reactors or bioreactors, carriers capable of cargo loading and release, and scaffolds for nanotemplating. However, despite their structural similarity to lipid cubosomes and applicability, polymer cubosomes have been only sporadically observed as an outcome of serendipity until recent studies demonstrated that BCPs could form well-defined polymer cubosomes in solution.In this Account, we describe our recent progress in creating polymer cubic mesophases and their colloidal particles (polymer cubosomes) in dilute solution. BCPs with nonlinear architectures (dendritic-linear, branched-linear, and branched-branched BCPs) preferentially self-assembled to inverse mesophases in solution when the block ratio (f), defined as a molecular weight ratio of the hydrophilic block to that of the hydrophobic block, was small (<10%). The resulting lyotropic structures transformed from flat bilayers to cubic phases of primitive cubic and double diamond lattices and finally to inverted hexagonal phases as f decreased. We proposed that the architecture of a BCP plays an important role in the preferential formation of polymer cubosomes in solution. The presence of the bulky hydrophilic block limited chain stretching of the hydrophobic polymer block, which would increase the packing parameter of the BCP to greater than unity, a prerequisite for inverse mesophase formation. The structural characteristics of polymer cubosomes, such as lattice symmetries, pore sizes, and lattice parameters, could also be controlled by fine-tuning the structural parameters of BCPs. We also suggested nonsynthetic methods to precisely control the phase and internal lattice of inverse mesophases of BCPs by the coassembly of two BCPs with different block ratios (mix-and-match approach) and the modulation of the affinity of the common solvent toward the hydrophobic block of the BCP. To investigate the potential applications of polymer cubosomes, we prepared inorganic photonic crystals using a cubosome-templated synthesis. We also discussed the utilization of cubosomes as chemical reactors by functionalization of the surface and the covalent stabilization of transient self-assembled structures via cross-linking of the hydrophobic domain. This Account reflects the efforts of synthetic chemists to understand the self-assembly behavior of BCPs to form complex morphologies in solution. We hope that our Account inspires efforts from chemists and other scientists to further understand these structures with infinite mazes of complexity and possibility.

High-density information storage in an absolutely defined aperiodic sequence of monodisperse copolyester.

Synthesis of a polymer composed of a large discrete number of chemically distinct monomers in an absolutely defined aperiodic sequence remains a challenge in polymer chemistry. The synthesis has largely been limited to oligomers having a limited number of repeating units due to the difficulties associated with the step-by-step addition of individual monomers to achieve high molecular weights. Here we report the copolymers of α-hydroxy acids, poly(phenyllactic-co-lactic acid) (PcL) built via the cross-convergent method from four dyads of monomers as constituent units. Our proposed method allows scalable synthesis of sequence-defined PcL in a minimal number of coupling steps from reagents in stoichiometric amounts. Digital information can be stored in an aperiodic sequence of PcL, which can be fully retrieved as binary code by mass spectrometry sequencing. The information storage density (bit/Da) of PcL is 50% higher than DNA, and the storage capacity of PcL can also be increased by adjusting the molecular weight (~38 kDa).

Cross-Linked Polymersomes with Reversible Deformability and Oxygen Transportability.

Polymersomes are of interest as nanocarriers due to their physical and chemical robustness, which arises from the macromolecular nature of their block copolymer components. However, the physical robustness of polymersomes impairs transmembrane diffusion and responsiveness to mechanical forces. Polymer nanocarriers that can reversibly deform under stress while maintaining structural integrity and transmembrane diffusivity are desired for development of gas transport vehicles. Here, we report polymersomes composed of amphiphilic block copolymers containing polydimethylsiloxane with side-chain pendant vinyl groups. A reversibly deformable polymersome compartmentalizing membrane was obtained by cross-linkage of PEG- b-poly(dimethyl- r-methylvinyl)silane in a self-assembled bilayer via photoradical generation in aqueous media. The covalently cross-linked polymersomes exhibited superior physical robustness compared to unlinked polymersomes while maintaining deformability under stress. Transmembrane oxygen diffusion was confirmed when lumen-encapsulated Zn-porphyrin generated singlet O2 under irradiation, and the anthracene-9,10-dipropionic acid O2 quencher was consumed. Polymersome-encapsulated hemoglobin bound oxygen reversibly, indicating the polymersomes could be used as O2 carriers that reversibly deform without sacrificing structural integrity or oxygen transportability.

The effect of steric repulsion between highly branched hydrophilic blocks on inverse cubic mesophase formation in block copolymers.

The solution-based self-assembly of block copolymers (BCPs) into nanoparticulate or microparticulate inverse cubic mesophases, or polymer cubosomes, is of growing interest. This phenomenon could yield new polymeric mesoporous materials with three-dimensionally organized mazes of large water channels. In addition to the ratio of its hydrophilic and hydrophobic blocks, the architecture of a BCP critically influences self-assembly. BCP bilayers having triply periodic minimal surfaces with cubic lattice structures are formed. Here we report the synthesis and self-assembly of BCPs with T8 polyhedral oligomeric silsesquioxane (POSS), an inorganic cage molecule. POSS can be asymmetrically functionalized to host structural modules as branching units of the hydrophilic block that contain various spatial and chemical environments. BCPs, each containing seven poly(ethylene glycol) chains and the hydrophobic polystyrene block PEG3507-POSS-b-PS, were prepared to investigate the effect of the highly branched hydrophilic block architecture on self-assembly. We found that the BCPs self-assembled into polymer cubosomes. Regardless of the block ratio, only the primitive cubic phase (Schwarz P surface, Im3̄m space group) was observed in the cubosomes. This is in contrast to the self-assembly of conventional BCPs into inverse mesophases, in which the internal lattice preferentially transforms into double-diamond lattices to yield a Schwarz D surface as a consequence of block ratio changes. Our results suggest that BCP architecture may be related to the symmetry of the lattice formed via self-assembly in solution.

Templated synthesis of cubic crystalline single networks having large open-space lattices by polymer cubosomes.

The synthesis of biophotonic crystals of insects, cubic crystalline single networks of chitin having large open-space lattices, requires the selective diffusion of monomers into only one of two non-intersecting water-channel networks embedded within the template, ordered smooth endoplasmic reticulum (OSER). Here we show that the topology of the circumferential bilayer of polymer cubosomes (PCs)-polymeric analogues to lipid cubic membranes and complex biological membranes-differentiate between two non-intersecting pore networks embedded in the cubic mesophase by sealing one network at the interface. Consequently, single networks having large lattice parameters (>240 nm) are synthesized by cross-linking of inorganic precursors within the open network of the PCs. Our results pave the way to create triply periodic structures of open-space lattices as photonic crystals and metamaterials without relying on complex multi-step fabrication. Our results also suggest a possible answer for how biophotonic single cubic networks are created, using OSER as templates.

A Recombinant Secondary Antibody Mimic as a Target-specific Signal Amplifier and an Antibody Immobilizer in Immunoassays.

We construct a novel recombinant secondary antibody mimic, GST-ABD, which can bind to the Fc regions of target-bound primary antibodies and acquire multiple HRPs simultaneously. We produce it in tenth of mg quantities with a bacterial overexpression system and simple purification procedures, significantly reducing the manufacturing cost and time without the use of animals. GST-ABD is effectively conjugated with 3 HRPs per molecule on an average and selectively bind to the Fc region of primary antibodies derived from three different species (mouse, rabbit, and rat). HRP-conjugated GST-ABD (HRP-GST-ABD) is successfully used as an alternative to secondary antibodies to amplify target-specific signals in both ELISA and immunohistochemistry regardless of the target molecules and origin of primary antibodies used. GST-ABD also successfully serves as an anchoring adaptor on the surface of GSH-coated plates for immobilizing antigen-capturing antibodies in an orientation-controlled manner for sandwich-type indirect ELISA through simple molecular recognition without any complicated chemical modification.

A Morphological Transition of Inverse Mesophases of a Branched-Linear Block Copolymer Guided by Using Cosolvents.

We report here a strategy for influencing the phase and lattice of the inverse mesophases of a single branched-linear block copolymer (BCP) in solution which does not require changing the structure of the BCP. The phase of the self-assembled structures of the block copolymer can be controlled ranging from bilayer structures of positive curvature (polymersomes) to inverse mesophases (triply periodic minimal surfaces and inverse hexagonal structures) by adjusting the solvent used for self-assembly. By using solvent mixtures to dissolve the block copolymer we were able to systematically change the affinity of the solvent toward the polystyrene block, which resulted in the formation of inverse mesophases with the desired lattice by self-assembly of a single branched-linear block copolymer. Our method was also applied to a new solution self-assembly method for a branched-linear block copolymer on a stationary substrate under humidity, which resulted in the formation of large mesoporous films. Our results constitute the first controlled transition of the inverse mesophases of block copolymers by adjusting the solvent composition.