Fluorophore-Probed Curdlan Polysaccharide Chemosensor: "Turn-On" Oligosaccharide Sensing in Aqueous Media.

The ability to sense saccharides in aqueous media has attracted much attention in multidisciplinary sciences because the detection of ultrahigh concentrations of sugar chains associated with serious diseases could lead to further health promotion. However, there are notable challenges. In this study, a rhodamine-modified Curdlan (Rhod-Cur) chemosensor was synthesized that exhibited distinctive fluorescence "turn-on" responses. Rhod-Cur exhibited simultaneous sensitive and selective sensing of clinically useful acarbose with a good limit of detection (5 µM) from among those of the saccharides examined. The (chir)optical properties of Rhod-Cur were elucidated using UV/vis, fluorescence, excitation, and circular dichroism spectroscopies; lifetime measurements and morphological studies using atomic force and confocal laser scanning microscopy and dynamic light scattering techniques revealed that the fluorescence "turn-on" behavior originates from globule-to-coaggregation conversion upon insertion of the oligosaccharides in the dynamic Cur backbone.

Correction: Ionic supramolecular polymerization of water-soluble porphyrins: balancing ionic attraction and steric repulsion to govern stacking.

[This corrects the article DOI: 10.1039/D2RA05542B.].

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.

Ionic supramolecular polymerization of water-soluble porphyrins: balancing ionic attraction and steric repulsion to govern stacking.

We have synthesized novel water-soluble anionic porphyrin monomers that undergo pH-regulated ionic supramolecular polymerization in aqueous media. By tuning the total charge of the monomer, we selectively produced two different supramolecular polymers: J- and H-stacked. The main driving force toward the J-aggregated supramolecular polymers was the ionic interactions between the sulfonate and protonated pyrrole groups, ultimately affording neutral supramolecular polymers. In these J-aggregated supramolecular polymers, amide groups were aligned regularly along polymer wedges, which further assembled in an edge-to-edge manner to afford nanosheets. In contrast, the H-aggregated supramolecular polymers remained anionic, with their amide NH moieties acting as anion receptors along the polymer chains, thereby minimizing repulsion. For both polymers, varying the steric bulk of the peripheral ethylene glycol (EG) units controlled the rates of self-assembly as well as the degrees of polymerization. This steric effect was further tunable, depending on the solvation state of the EG chains. Accordingly, this new family of supramolecular polymers was created by taking advantage of unique driving forces that depended on both the pH and solvent.

Geometrical pH mapping of Microfluids by principal-component-analysis-based xyz-spectrum conversion method.

The absorption spectra of bromothymol blue (BTB) solution introduced in microfluidic devices were reproduced by principal component analysis (PCA)-based xyz-spectrum conversion methods for geometric mapping of the pH values of fluids. We fabricated PDMS-made microfluidic devices with a channel depth of 1 mm to overcome the lower detection limits of transmittance image acquisition. Aqueous solutions of pH indicators under various pH conditions were hydrodynamically introduced into the channel, and RGB values of the region of interest (ROI) were obtained via image analysis. The xyz values were then converted into absorption spectral data of the pH indicator using the PCA-based spectral reproduction previously proposed by the authors. The high reproducibility of the spectra was confirmed to be comparable to that of the conventional method using a spectrophotometer. We applied the present method to elucidate the pH gradient at an aqueous biphasic interface in the microfluidic channels generated by contacting multiple laminar flows of two or three buffered solutions. We confirmed that the pH gradient ranged from approximately 70 to 140 µm, which is consistent with the results reported using other approaches. The results demonstrate the applicability of the present method to the fluctuation field in micro/nanospaces to acquire spectrophotometric information in the order of milliseconds without monochromating equipment.

Directional Supramolecular Polymerization in a Dynamic Microsolution: A Linearly Moving Polymer's End Striking Monomers.

Although directional chain reactions are common in nature's self-assembly processes and in covalent polymerizations, it has been challenging to perform such processes in artificial one-dimensional self-assembling systems. In this paper, we describe a system, employing perylene bisimide (PBI) derivatives as monomers, for selectively activating one end of a supramolecular polymer during its growth and, thereby, realizing directional supramolecular polymerization. Upon introduction of a solution containing only a single PBI monomer into the microflow channel, nucleation was induced spontaneously. The dependency of the aggregation efficiency on the flow rate suggested that the shear force facilitated collisions among the monomers to overcome the activation energy required for nucleation. Next, by introducing a solution containing both monomer and polymer, we investigated how the shear force influenced the monomer-polymer interactions. In situ fluorescence spectra and linear dichroism revealed that growth of the polymers was accelerated only when they were oriented under the influence of shear stress. Upon linear motion of the oriented polymer, polymer growth at that single end became predominant relative to the nucleation of freely diffusing monomers. When applying this strategy to a two-monomer system, the second (less active) monomer reacted selectively at the forward-facing terminus of the first polymer, leading to the creation of a diblock copolymer through formation of a molecular heterojunction. This strategy-friction-induced activation of a single end of a polymer-should be applicable more generally to directional supramolecular block copolymerizations of various functional molecules, allowing molecular heterojunctions to be made at desired positions in a polymer.

Microflow system promotes acetaminophen crystal nucleation.

It is known that interfaces have various impacts on crystallization from a solution. Here, we describe crystallization of acetaminophen using a microflow channel, in which two liquids meet and form a liquid-liquid interface due to laminar flow, resulting in uniform mixing of solvents on the molecular scale. In the anti-solvent method, the microflow mixing promoted the crystallization more than bulk mixing. Furthermore, increased flow rate encouraged crystal formation, and a metastable form appeared under a certain flow condition. This means that interface management by the microchannel could be a beneficial tool for crystallization and polymorph control.

Oligosaccharide Sensing in Aqueous Media Using Porphyrin-Curdlan Conjugates: An Allosteric Signal-Amplification System.

A series of porphyrin-curdlan conjugates 1-5 of varying degree of substitution (DS) were synthesized to examine their morphological features, chiroptical properties, and oligosaccharide sensing in aqueous media, particularly for tetrasaccharide acarbose, which is a drug to treat type-2 diabetes. The random coil state of compounds 1-5 in DMSO becomes the globule curdlan-saccharide coaggregate upon interaction of acarbose in aqueous DMSO solution to induce various circular dichroism (CD) responses. The high cooperativity and positive homotropic allosterism were observed in the acarbose recognition, enabling the allosteric signal-amplification sensing, for which the DS, stacking character, and microenvironmental polarity changes of the tethered porphyrin reporters are likely to be responsible.

Oligosaccharide Sensing in Aqueous Media by Porphyrin-Curdlan Conjugates: A Prêt-á-Porter Rather Than Haute-Couture Approach.

Saccharide sensing in aqueous media is an intriguing but challenging goal in current chemistry. Herein we report the oligosaccharide-sensing behavior of newly synthesized porphyrin-curdlan conjugates, which are random coils in DMSO but become globules in aqueous solutions to induce circular dichroism (ICD) in the biologically accessible spectral region due to the conformational fixation of porphyrin reporters. The magnitude of ICD was significantly varied specifically in the presence of acarbose, a drug for type-2 diabetes, enabling us to detect the aminosaccharide at concentrations down to 200 µm. This result demonstrates that the prêt-á-porter approach, using less-defined reporter-curdlan conjugates, is more advantageous than the traditional haute-couture approach with highly sophisticated hosts in particular in oligosaccharide sensing.

Supramolecular Chemistry in Microflow Fields: Toward a New Material World of Precise Kinetic Control.

Constructing new and versatile self-assembling systems in supramolecular chemistry is much like the development of new reactions or new catalysts in synthetic organic chemistry. As one such new technology, conventional supramolecular assembly systems have been combined with microflow techniques to control intermolecular or interpolymer interactions through precise regulation of a flowing self-assembly field. The potential of the microflow system has been explored by using various simple model compounds. Uniform solvent diffusion in the microflow leads to rapid activation of molecules in a nonequilibrium state and, thereby, enhanced interactions. All of these self-assembly processes begin from a temporally activated state and proceed in a uniform chemical environment, forming a synchronized cluster and resulting in effective conversion to supramolecules, with precise tuning of molecular (or polymer) interactions. This approach allows the synthesis of a variety of discrete microstructures (e.g., fibers, sheets) and unique supramolecules (e.g., hierarchical assemblies, capped fibers, polymer networks, supramolecules with time-delayed action) that have previously been inaccessible.

Two-dimensional assembly based on flow supramolecular chemistry: kinetic control of molecular interactions under solvent diffusion.

Self-assembly of porphyrin molecules can be controlled kinetically to form structures with lengths extending from the nano- to the micrometer scale, through a programmed solvent-diffusion process in designed microflow spaces. Temporal solvent structures generated in the microflow were successfully transcribed into molecular architectures.

Two-dimensional self-assembly of amphiphilic porphyrins on a dynamically shrinking droplet surface.

Developing a new field of molecular self-assembly in the sub-micrometer regime-with precision as high as that used to make discrete nano-sized molecular architectures through molecular design-is a major challenge for supramolecular chemistry. At present, however, there is no effective strategy for controlling the assembling molecules when their quantity is greater than one thousand. Herein, we propose a potential solution by exploiting a novel supramolecular system in conjunction with dynamically shrinking oil droplets, enabling more than a thousand component molecules to organize simultaneously into the form of sub-micrometer-scale ring structures. In our developed system, amphiphilic porphyrins, having potential two-dimensional assembling ability, were compartmentalized into droplets with narrow distributions and molecular numbers. These droplets were subsequently transformed into discrete ring-like structures during the process of solvent removal from the inner organic layer, i.e., shrinking the droplets. Unique self-assembled structures, which are not accessible through conventional supramolecular strategies, can be selectively created depending on the initial stage of the droplet.

Supramolecular polymerization in microfluidic channels: spatial control over multiple intermolecular interactions.

A novel supramolecular assembly has been developed in conjugation with microfluidics. Self-assembly of the programmed molecules was controlled precisely, in space and time, in a microflow channel as a result of a homogeneous solvent mixing process. Furthermore, through continuous organization of component molecules followed by orientation along microflow, the self-assembling event containing different molecules was spatially controlled from nano to micrometer scale in a single stream (GMP=guanosine 5'-monophosphate).

Controlled stacking and unstacking of peripheral chlorophyll units drives the spring-like contraction and expansion of a semi-artificial helical polymer.

Developing new strategies for controlling polymer conformations through precise molecular recognition can potentially generate a machine-like motion that is dependent on molecular information-an important process for the preparation of new intelligent nanomaterials (e.g., polymer-based nanomachines) in the field bordering between polymer chemistry and conventional supramolecular sciences. Herein, we propose a strategy to endow a helical polymer chain with dynamic spring-like (contraction/expansion) motion through the one-dimensional self-assembly (aggregation/disaggregation) of peripheral amphiphilic molecules. In this developing system, we employed a semi-artificial helical polysaccharide presenting peripheral amphiphilic chlorophyll units as a power device that undergoes contractive motion in aqueous media, driven by strong π-π interactions of its chlorophyll units or by cooperative molecular recognition of bipyridyl-type ligands through pairs of chlorophyll units, thereby converting molecular information into the regulated motion of a spring. In addition, this system also undergoes expansive motion through coordination of pyridine. We anticipate that this strategy will be applicable (when combined with the established wrapping chemistry of the helical polysaccharide) to the development of, for example, drug carriers (e.g., nano-syringes), actuators (stimuli-responsive films), and directional transporters (nano-railways), thereby extending the frontiers of supramolecular science.

Hierarchical supramolecular spinning of nanofibers in a microfluidic channel: tuning nanostructures at a dynamic interface.

One of the fundamental problems in supramolecular chemistry, as well as in material sciences, is how to control the self-assembly of polymers on the nanometer scale and how to spontaneously organize them towards the macroscopic scale. To overcome this problem, inspired by the self-assembly systems in nature, which feature the dynamically controlled self-assembly of biopolymers, we have previously proposed a self-assembly system that uses a dynamic liquid/liquid interface with dimensions in the micrometer regime, thereby allowing polymers to self-assemble under precisely controlled nonequilibrium conditions. Herein, we further extend this system to the creation of hierarchical self-assembled architectures of polysaccharides. A natural polysaccharide, ß-1,3-glucan (SPG), and water were injected into opposite "legs" of microfluidic devices that had a Y-shape junction, so that two solvents would gradually mix in the down stem, thereby causing SPG to spontaneously self-assemble along the flow in a head-to-tail fashion, mainly through hydrophobic interactions. In the initial stage, several SPG nanofibers would self-assemble at the Y-junction owing to the shearing force, thereby creating oligomers with a three-way junction point. This unique structure, which could not be created through conventional mixing procedures, has a divergent self-assembly capability. The dynamic flow allows the oligomers to interact continuously with SPG nanofibers that are fed into the Y-junction, thus amplifying the nanostructure along the flow to form SPG networks. Consequently, we were able to create stable, centimeter-length macroscopic polysaccharide strands under the selected flow conditions, which implies that SPG nanofibers were assembled hierarchically in a supramolecular fashion in the dynamic flow. Microscopic observations, including SEM and AFM analysis, revealed the existence of clear hierarchical structures inside the obtained strand. The network structures self-assembled to form sub-micrometer-sized fibers. The long fibers further entangled with each other to give stable micrometer-sized fibers, which finally assembled to form the macroscopic strands, in which the final stabilities in the macroscopic regime were governed by that of the network structures in the nanometer regime. Thus, we have exploited this new supramolecular system to create hierarchical polymeric architectures under precisely controlled flow conditions, by combining the conventional supramolecular strategy with microfluidic science.

'Supramolecular wrapping chemistry' by helix-forming polysaccharides: a powerful strategy for generating diverse polymeric nano-architectures.

We have exploited novel supramolecular wrapping techniques by helix-forming polysaccharides, ß-1,3-glucans, which have strong tendency to form regular helical structures on versatile nanomaterials in an induced-fit manner. This approach is totally different from that using the conventional interpolymer interactions seen in both natural and synthetic polymeric architectures, and therefore has potential to create novel polymeric architectures with diverse and unexpected functionalities. The wrapping by ß-1,3-glucans enforces the entrapped guest polymer to adopt helical or twisted conformations through the convergent interpolymer interactions. On the contrary, the wrapping by chemically modified semi-artificial ß-1,3-glucans can bestow the divergent self-assembling abilities on the entrapped guest polymer to create hierarchical polymeric architectures, where the polymer/ß-1,3-glucan composite acts as a huge one-dimensional building block. Based on the established wrapping strategy, we have further extended the wrapping techniques toward the creation of three-dimensional polymeric architectures, in which the polymer/ß-1,3-glucan composite behaves as a sort of amphiphilic block copolymers. The present wrapping system would open several paths to accelerate the development of the polymeric supramolecular assembly systems, giving the strong stimuli to the frontier of polysaccharide-based functional chemistry.

Hierarchical polymer assemblies constructed by the mutual template effect of cationic polymer complex and anionic supramolecular nanofiber.

Creation of higher-ordered polymeric architectures composed of alternative assemblies of single-walled carbon nanotubes (SWNTs) and fibrous porphyrin J-aggregates can be easily achieved utilizing the cationic semi-artificial polysaccharide which can act not only as a tubular host for SWNTs but also as a one-dimensional template for porphyrin molecules. This new class of hierarchical polymer assembly is formed, for the first time, by the mutual template effect of two components, i.e., the cationic SWNT complexes and the anionic porphyrin supramolecular nanofibers. In the present system, the self-assembling behaviors of the SWNT complexes as well as the final properties of the SWNT nanoarchitectures are strongly affected by the packing mode of porphyrin molecules on the cationic semi-artificial polysaccharide. Furthermore, we have confirmed that the light energy captured by the porphyrin J-aggregates is effectively transferred to SWNTs.

"Supramolecular" amphiphiles created by wrapping poly(styrene) with the helix-forming beta-1,3-glucan polysaccharide.

We have demonstrated that giant polymer micelles with a uniform diameter (ca. 200 nm) can be fabricated by "supramolecular wrapping" of poly(styrene) (PS) with the beta-1,3-glucan polysaccharide, with the beta-1,3-glucan fastening the PS chains together in a noncovalent fashion to facilitate the formation of a supramolecular polymer network on the O/W emulsion surface. Various spectroscopic and microscopic investigations have revealed that the inner cores of the micelles are comprised of a hydrophobic PS network, whereas the surfaces consist of a hydrophilic beta-1,3-glucan layer. Accordingly, functional guest molecules can easily be encapsulated inside the cavity through hydrophobic interactions. The encapsulated molecules can simply be released from the micelle cores by peeling off the beta-1,3-glucan shell in a supramolecular manner. As functional groups can be introduced into the glucose side-chain unit in a straightforward manner by chemical modification, the micellar surface can acquire further functions useful for molecular recognition. These results show that the micelles obtained could have applications as novel soft nanoparticles, which would be indispensable not only for nanotechnologies, but also for biotechnologies aimed at gene or drug delivery systems.

Alternate layer-by-layer adsorption of single- and double-walled carbon nanotubes wrapped by functionalized beta-1,3-glucan polysaccharides.

A great deal of attention has been focused on exploiting novel methods to fabricate thin carbonaceous capsules from multiple components for advanced materials. A layer-by-layer (LbL) method is therefore being introduced to synthesize thin and multi-carbon nanotube (CNT)-based hollow capsules from CNT complexes with cationic or anionic complementarily functionalized beta-1,3-glucans as building-blocks. These ionic beta-1,3-glucans wrap around single-walled carbon nanotubes (SWNTs) and double-walled carbon nanotubes (DWNTs) to form water-soluble complexes with ionic groups on their exterior surface. Alternate self-assembly of these CNT complexes on the silica particles is demonstrated in solution by electrostatic interactions. The LbL adsorption processes were carefully monitored by zeta-potential measurements, frequency shifts of a quartz crystal microbalance (QCM), and electron micrographs. Silica particles were then dissolved away by HF acid to obtain CNT-based hollow capsules composed of SWNTs and DWNTs. We believe that these novel surface adsorption methods are useful for potential design of CNT-based advanced functional materials.