"Dynamic" molecular recognition and chirality segregation utilizing concepts of molecular machines and molecular assemblies.

The need to measure the concentration of selected ions and small organic molecules in both in vivo and in vitro processes is continuously increasing beyond the borders of various research fields. This need has been fulfilled using "host-guest chemistry", or in general, by the use of "molecular recognition". The basic idea in these research fields was derived from the 1 : 1 host-guest interaction based on the "key-and-lock" concept. However, we have experienced that only with this classical concept, more precise, higher-order recognition faces serious difficulty. In this review article, I wish to explain that the introduction of two new concepts, i.e., the dynamic action of molecular systems and the amplification effect of molecular assemblies, overcame the limitation of the "key-and-lock" concept. In fact, we have found that even "complete" chirality segregation can be achieved under optimal conditions.

Amylose-grafted Curdlan: A New Class of Semi-artificial Branched Polysaccharides for Hierarchical Polymeric Superstructures Created by the Action of "Orthogonal" Binding Sites.

The semi-artificial branched-polysaccharides, amylose-grafted curdlans, were synthesized utilizing an enzymatic polymerization. Both a curdlan main chain and amylose side chains on the polysaccharides maintain the original helical structure as well as the molecular binding ability. Thanks to the difference in their molecular recognition properties between ß-1,3-glucan chain and α-1,4-glucan chain, the amylose-grafted curdlans can provide two different orthogonal binding sites within one polymeric system. When a water-soluble polythiophene was mixed with the amylose-grafted curdlan, the polythiophene was twisted in two different modes and therein, fluorescence energy of the polythiophene wrapped by the amylose side chains was successfully transferred to the polythiophene wrapped by the curdlan main chain. We thus concluded that in the dendritic superstructure of this polysaccharide, a self-organized "Janus-type FRET system" was successfully constructed.

Design of a Hypersensitive pH-Sensory System Created by a Combination of Charge Neutralization and Aggregation-Induced Emission (AIE).

In our bodies, a slight pH change causes remarkable activation or serious damage in the biological processes and continuously keeps biological homeostasis. Detection of such a slight pH change has been a constant demand in searching for unusual biological events. In this paper, we demonstrate a novel pH sensory system that has been achieved through a combination of charge neutralization by a slight pH change with aggregation-induced emission (AIE). We selected a cyano-functionalized oligo(phenylene-vinylene) (cyanoOPV) backbone for AIE and introduced ammonium-tethered boronic acid groups as a pH-dependent function. The self-assembling of these dyes (OPV-Cn) was readily achieved by pH-dependent charge neutralization at the neutral pH region. This sensory system showed unusually sensitive pH responsiveness in a narrow pH range. Moreover, this pH change was observed in a biologically important neutral pH region. We therefore believe that this system is broadly applicable to detect the slight pH change occurring in the biological events.

A Chiral Recognition System Orchestrated by Self-Assembly: Molecular Chirality, Self-Assembly Morphology, and Fluorescence Response.

The newly developed oligophenylenevinylene (OPV)-based fluorescent (FL) chiral chemosensor (OPV-Me) for the representative enantiomeric guest, 1,2-cyclohexanedicarboxylic acid (1,2-CHDA: RR- and SS-form) showed the high chiral discrimination ability, resulting in the different aggregation modes of OPV-Me self-assembly: RR-CHDA directed the fibrous supramolecular aggregate, whereas SS-CHDA directed the finite aggregate. The consequent FL intensity toward RR-CHDA was up to 30 times larger than that toward SS-CHDA. Accordingly, highly enantioselective recognition was achieved. Application to the chirality sensing was also possible: OPV-Me exhibited a linear relationship between the FL intensity and the enantiomeric excess through the morphological development of stereocomplex aggregates. These results clearly show that the chiral recognition ability is manifested by the amplification cascade of the chirality difference through self-assembly.

Cohelical Crossover Network by Supramolecular Polymerization of a 4,6-Acetalized ß-1,3-Glucan Macromer.

Natural polysaccharides represent a renewable resource whose effective utilization is of increasing importance. Chemical modification is a powerful tool to transform them into processable materials but usually sacrifices the original structures and properties of value. Here we introduce a chemical modification of Curdlan, a ß-1,3-glucan, via 4,6-acetalization. This modification has successfully combined a helix-forming ability of Curdlan with new solubility in organic media. Furthermore, it has operationalized efficient cohelical crossovers (CCs) among the helices to demonstrate the formation of an extensive supramolecular network that goes well beyond the nanoscopic regime, allowing for preparation of flexible self-supporting films with macroscopic dimensions. This protocol, which is now viewed as supramolecular polymerization of a helical polysaccharide macromer, can add a new dimension to "polysaccharide nanotechnology", opening a door for the creation of unconventional polymer materials based on the cohelical crossover network (CCN).

Adaptive Self-Assembly Behavior Restrained by Supramolecular Crystallization and Molecular Recognition.

The control over supramolecular interactions and obtaining information beyond the molecular scale is an extended challenge. The intriguing self-assembly of a perylene-3,4,9,10-tetracarboxylic acid diimide (PDI)-based novel bolaamphiphilic probe is experienced within an artificial environment that is restrained by using supramolecular crystallization and molecular recognition. The bolaamphiphile with a hydrophilic [18]-azacrown ether ring produced nanoaggregates due to differing solubilities in organic and aqueous media. A structural evolution was observed in the presence of alkali metal ions as guests. The metal complexes form a pseudo-cationic structure, which is further involved in an ionic self-assembly with biomolecules, thus resulting new spectroscopic information on the dye self-assembly. The overarching aim of this study is to emphasize the importance of the concept of supramolecular adaptability, which has been used to establish an environment-friendly behavior based on noncovalent forces, thus leading to the evolution of new assembly structures and photophysical properties.

Conformation Control of a Conjugated Polymer through Complexation with Bile Acids Generates Its Novel Spectral and Morphological Properties.

Control of higher-order polymer structures attracts a great deal of interest for many researchers when they lead to the development of materials having various advanced functions. Among them, conjugated polymers that are useful as starting materials in the design of molecular wires are particularly attractive. However, an equilibrium existing between isolated chains and bundled aggregates is inevitable and has made their physical properties very complicated. As an attempt to simplify this situation, we previously reported that a polymer chain of a water-soluble polythiophene could be isolated through complexation with a helix-forming polysaccharide. More recently, a covalently self-threading polythiophene was reported, the main chain of which was physically protected from self-folding and chain-chain π-stacking. In this report, we wish to report a new strategy to isolate a water-soluble polythiophene and to control its higher-order structure by a supramolecular approach: that is, among a few bile acids, lithocholate can form stoichiometric complexes with cationic polythiophene to isolate the polymer chain, and the higher-order structure is changeable by the molar ratio. The optical and morphological studies have been thoroughly performed, and the resultant complex has been applied to the selective recognition of two AMP structural isomers.

Emergent Molecular Recognition through Self-Assembly: Unexpected Selectivity for Hyaluronic Acid among Glycosaminoglycans.

Oligophenylenevinylene (OPV)-based fluorescent (FL) chemosensors exhibiting linear FL responses toward polyanions were designed. Their application to FL sensing of glycosaminoglycans (heparin: HEP, chondroitin 4-sulfate: ChS, and hyaluronic acid: HA) revealed that the charge density encoded as the unit structure directs the mode of OPV self-assembly: H-type aggregate for HEP with 16-times FL increase and J-type aggregate for HA with 93-times FL increase, thus unexpectedly achieving the preferential selectivity for HA in contrast to the conventional HEP selective systems. We have found that the integral magnitude of three factors consisting of binding mechanism, self-assembly, and FL response can amplify the structural information on the target input into the characteristic FL output. This emergent property has been used for a novel molecular recognition system that realizes unconventional FL sensing of HA, potentially applicable to the clinical diagnosis of cancer-related diseases.

Amplified fluorescence emission of bolaamphiphilic perylene-azacrown ether derivatives directed towards molecular recognition events.

Long-term creative approaches have been considered in the design of molecular probes to overcome the quenching effect of important dyes in an aqueous medium. Using the rational donor-acceptor based design principle, we demonstrate herein the different fluorescence states of a non-conjugated symmetrical perylene-azacrown ether system in a solution, from the molecular to the aggregated states. The ethylene-spacer is exceptionally capable of fluorescence enhancement, even in the aggregated state (organic nanoparticle, ONPs, 44 nm), overcoming the quenching effect on changing the solvent from tetrahydrofuran to water. The ONPs with crown ether receptors at the surface show colloidal stability in an aqueous solution. Furthermore, an improved fluorescent state is developed via ONPs-polymer (protamine, Pro) hybridization. Supramolecular interactions between the crown ring and the guanidinium group in Pro play an important role in the ONPs-Pro hybrid formation. The decorated fluorescent hybrid state is finally used as a nano-probe for sensing heparin via the turn-OFF mechanism. The decoration method is further generalized by recognition of the nucleotides. Herein, we detail the bottom-up approach to the molecular design and development of the different fluorescent states of a useful probe. Most excitingly, this new approach is very general and adaptive to facile detection.

Supramolecular assembly of achiral alkynylplatinum(II) complexes and carboxylic ß-1,3-glucan into different helical handedness stabilized by Pt⋠⋠⋠Pt and/or π-π interactions.

Two-component ensembles of alkynylplatinum(II) terpyridine (tpy) complexes and carboxylic ß-1,3-glucan (CurCOOH) have been investigated by using spectroscopic and microscopic techniques, as well as time-dependent UV/Vis absorption and circular dichroism (CD) experiments. Microscopic images of [Pt(tpy){C≡CC6 H4 (CH2 NMe3 -4)}](OTf)2 (1) have revealed spherical nanostructures, whereas helical fibrous structures of different lengths, depending on the concentration of complex 1 and CurCOOH, were observed. The helical assemblies have been found to show low-energy metal-metal-to-ligand charge transfer (MMLCT) absorption and triplet MMLCT ((3) MMLCT) emission, which are indicative of Pt⋅⋅⋅Pt and/or π-π interactions between the complex 1 molecules. Interestingly, the ensemble has been demonstrated to show different handedness and even a change in handedness over time under different experimental conditions. Low temperatures, low concentrations of CurCOOH, high concentrations of complex 1, or successive addition of CurCOOH into complex 1 solution favor the formation of right-handed helical assemblies, whereas high temperatures, high concentrations of CurCOOH, low concentrations of complex 1, or single-batch addition of CurCOOH into complex 1 solution result in a fast chiroptical inversion of the ensemble solution, giving rise to the left-handed helical assemblies as the dominant species. The results have been rationalized by considering the competing kinetically and thermodynamically controlled assembly-elongation of the ensemble, which leads to the formation of right-handed and left-handed helical assemblies, respectively. The change in the handedness of the ensemble has been demonstrated to stem from the formation of two-component assemblies with supramolecular interactions, in contrast to the template- induced chiral amplification commonly observed in other systems.

Tailoring of the desired selectivity and the turn-on detection range in a self-assembly-based fluorescence sensory system.

This study demonstrates how to control the selectivity and the turn-on detection range toward the tailoring of an assembly-based fluorescence (FL) sensory system. Assembly-based FL chemosensors composed of oligophenylenevinylene with a varied number of guanidinium receptors (G2, G4 and G6) were newly developed, and their FL response to nucleotides (AMP, ADP and ATP) was investigated. Indeed, G6 exhibited FL emission via self-assembly with ATP. More importantly, the FL response of G6 showed markedly improved selectivity for ATP over ADP and a broadly extended detection range of ATP concentration under adjusted salt conditions. The salt effect on the FL response revealed the competitive binding interactions affecting the subsequent self-assembly process. These studies have unveiled the pivotal binding mechanisms operating in the self-assembly process, which tailor the performance level of the assembly-based sensory system. We believe that this study offers a new design principle of an assembly-based FL chemosensor with high selectivity and the appropriate detection range, being different from the conventional key-and-lock system.

Translation of dicarboxylate structural information to fluorometric optical signals through self-assembly of guanidinium-tethered oligophenylenevinylene.

Although self-assembly has realized the spontaneous formation of nanoarchitectures, the nanoscopic expression of chemical structural information at the molecular level can alternatively be regarded as a tool to translate molecular structural information with high precision. We have found that a newly developed guanidinium-tethered oligophenylenevinylene exhibits characteristic fluorescence (FL) responses toward L- and meso-tartarate, wherein the different self-assembly modes, termed J- or H-type aggregation, are directed according to the molecular information encoded as the chemical structure. This morphological difference originates from the geometric anti versus gauche conformational difference between L- and meso-tartarate. A similar morphological difference can be reproduced with the geometric C=C bond difference between fumarate and maleate. In the present system, the dicarboxylate structural information is embodied in the inherent threshold concentration of the FL response, the signal-to-noise ratio, and the maximum FL wavelength. These results indicate that self-assembly is meticulous enough to sense subtle differences in molecular information and thus demonstrate the potential ability of self-assembly for the expression of a FL sensory system.

Luminescent calix[4]arene-based metallogel formed at different solvent composition.

We have synthesized a calix[4]arene derivative (1) containing terpyridine and showed that gelation occurred in the presence of Pt(2+) in DMSO/H2O of varying compositions. Gelation was presumably mediated by the Pt-Pt and π-π stacking interactions. The scanning electron microscopy image of the xerogel showed a spherical structure with diameter of 1.8-2.1 µm. Interestingly, the metallogel showed strong luminescence enhancement, which was dependent on the DMSO/H2O ratio of the solvent. We examined the effects of concentration, temperature, and time resolution on the luminescence emission of both the gel 1-Pt(2+) and the sol 1-Pt(2+). The luminescence lifetimes of the metallogel were particularly long, on the order of several microseconds. The luminescence lifetimes were also strongly dependent on the solvent composition. We also determined the thermodynamic parameters for the self-assembly of the gel by the Birks kinetic scheme. Furthermore, the rheological properties of the metallogels in the presence of more than 4.0 equiv of Pt(2+) were independent of the concentration of Pt(2+) applied.

Geometric change of a thiacalix[4]arene supramolecular gel with volatile gases and its chromogenic detection for rapid analysis.

A coordination polymer gel that is self-assembled to form a network structure between a thiacalix[4]arene derivative (L) and Co(2+) has been prepared. This gel is capable of selectively changing color in the presence of gases that yield hydrogen chloride upon hydrolysis. The UV-vis absorption spectrum of a coordination polymer gel derived from Co(NO3)2 exhibits an absorption band at 527 nm and is colored red, indicating the formation of an octahedral Co(2+) complex. Treatment with a small amount of volatile gases containing a chlorine atom (VGCl) causes a red shift of ∼150 nm, resulting in a new strong band with a maximum at 670 nm and a color change to blue. In addition, the red color of the filter paper coated with a Co(NO3)2 coordination polymer gel changed to blue upon exposure to VGCl, reflecting a change in the coordination geometry. Red and blue colors of single crystals of Co(2+) complexes were obtained from a basic solution. From X-ray crystallographic analysis, the red Co(2+) complex corresponds to an octahedral structure, while the blue Co(2+) complex reflects the presence of a tetrahedral structure. Thus, the induced color change of Co(2+) gel from red to blue upon exposure to VGCl is due to the coordination geometry. The quantitative concentration of VGCl was calculated by employing the RGB histogram available in a smartphone application.

Giant amino acids designed on the polysaccharide scaffold and their protein-like structural interconversion.

Amphoteric ß-1,3-glucans possessing both amino groups and carboxylic acid groups on the C6 positions of glucose units were designed and synthesized from naturally produced curdlan. The amphoteric polysaccharides showed the isoelectric point and the pH responsive interconversion between the original triple helix and single-stranded random structures. Since the pH dependences are comparable to the typical properties of proteins, the polysaccharides can be considered as a new class of giant amino acids. Utilizing the pH responsiveness, pH-controlled catch-and-release has been realized for cationic peptides or anionic DNA. We believe that the amphoteric polysaccharide can act as a new potential polymer to construct stimuli-responsive smart materials on the basis of the polysaccharide scaffold.

Cyclization-induced turn-on fluorescence system applicable to dicarboxylate sensing.

A novel tetraphenylethene-based fluorescence (FL) chemosensor exhibits nonlinear turn-on FL switching though cooperative binding of L-tartarate, where its convergent binding to form cyclic substructures is responsible for the FL increase. This binding scheme achieves selective detection of dicarboxylates over monocarboxylates, thus is potentially applicable to the preliminary screening for metabolic disorders.

Nucleotide sensing with a perylene-based molecular receptor via amplified fluorescence quenching.

A competitive fluorescence assay of perylene-based molecular receptors has been established, and selective detection of UTP is achieved through improved aggregation arising from the specific interaction of perylene-tethered guanidinium with uridine and phosphate groups in UTP.

Creation of circularly polarized luminescence from an achiral polyfluorene derivative through complexation with helix-forming polysaccharides: importance of the meta-linkage chain for helix formation.

A circularly polarized luminescence (CPL) material has been created by polymer-polymer complexation between a helix-forming polysaccharide, schizophyllan (SPG), and a meta-phenylene-linked polyfluorene derivative (mPFS). Computational modeling revealed that mPFS can adopt a helical structure although a conventional polyfluorene derivative with a para-phenylene linkage tends to enjoy a rigid rodlike conformation. Our detailed experimental examination showed that mPFS forms a chiral nanowire complex through cohelix formation with SPG. We have found, as expected, that this cohelical complex emits highly efficient CPL even in an aqueous solution. The appearance of the high CPL property is due to 1) a high quantum yield of the fluorene unit and 2) immobilization of the helically twisted conformation of mPFS in an isolated manner through cohelix formation with SPG. One can propose, therefore, that the SPG/mPFS complex acts as a new high-performance CPL material with a solvent-dispersible nanowire structure.

Cyclodextrin-assisted synthesis of a metallosupramolecular terbium(III) polymer and its fluorescence properties and chiral recognition.

Hold and connect! Inclusion of a bridging ligand into cyclodextrin (CD), followed by the addition of Tb(III) leads to a polyrotaxane-type metallosupramolecular polymer (see figure, L=4,4'-biphenyldicarboxylic acid). This polymer can recognize chirality and differentiate enantiomers by fluorescence and circular dichroism spectral changes.

Cross-linked conjugated polymer assemblies at the air-water interface through supramoleculer bundling.

We demonstrated conjugated polymer assemblies formed by coordination interaction with a porphyrinatozinc cross-linker at the air-water interface by means of the Langmuir-Blodgett technique. The coordination bonds were maintained at the interface, though the spacing between the polymer backbones in the Langmuir film was smaller than that in bulk solution, probably because of the influence of the interface. The successful transfer of the films to a substrate enabled the fabrication of a large-scale conjugated polymer material.