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.

Supramolecular nanosheet formation-induced photosensitisation mechanism change of Rose Bengal dye in aqueous media.

Development of two-dimensional materials and exploration of their functionalities are significant challenges due to their potential. In this study, we successfully fabricated a supramolecular nanosheet composed of amphiphilic Rose Bengal dyes in an aqueous medium. Furthermore, we elucidated a distinct change in the photosensitisation mechanism induced by nanosheet formation.

Preparation and temperature-controlled morphology of helical microrods composed of supramolecular α-cyclodextrin assemblies.

Significant efforts have been devoted so far to artificially fabricate supramolecular helical nano- and microstructures through the regulated assembly of biological and synthetic building blocks. However, the preparation of supramolecular helical structures with a regulated morphology remains challenging. Here, helical microrods composed of supramolecular α-cyclodextrin (α-CD) assemblies were fabricated by allowing an α-CD/1,1,1,3,3,3-hexafluoro-2-propanol (HFIP)/2-pentanol mixture to stand at 30-60 °C under high humidity conditions. The morphology could be controlled by temperature to produce helical microrods with a regulated pitch and length. These helical rods can be applied as optical devices, chiral separation devices and asymmetric catalysts.

Radioluminescence from polymer dots based on thermally activated delayed fluorescence.

We demonstrate that polymer dots doped with thermally activated delayed fluorescence (TADF) molecules clearly exhibit blue radio-luminescence upon hard X-ray and electron beam irradiation, which is a new design for nano-sized scintillators.

Sialylation shapes mucus architecture inhibiting bacterial invasion in the colon.

In the intestine, mucin 2 (Muc2) forms a network structure and prevents bacterial invasion. Glycans are indispensable for Muc2 barrier function. Among various glycosylation patterns of Muc2, sialylation inhibits bacteria-dependent Muc2 degradation. However, the mechanisms by which Muc2 creates the network structure and sialylation prevents mucin degradation remain unknown. Here, by focusing on two glycosyltransferases, St6 N-acetylgalactosaminide α-2,6-sialyltransferase 6 (St6galnac6) and ß-1,3-galactosyltransferase 5 (B3galt5), mediating the generation of desialylated glycans, we show that sialylation forms the network structure of Muc2 by providing negative charge and hydrophilicity. The colonic mucus of mice lacking St6galnac6 and B3galt5 was less sialylated, thinner, and more permeable to microbiota, resulting in high susceptibility to intestinal inflammation. Mice with a B3galt5 mutation associated with inflammatory bowel disease (IBD) also showed the loss of desialylated glycans of mucus and the high susceptibility to intestinal inflammation, suggesting that the reduced sialylation of Muc2 is associated with the pathogenesis of IBD. In mucins of mice with reduced sialylation, negative charge was reduced, the network structure was disturbed, and many bacteria invaded. Thus, sialylation mediates the negative charging of Muc2 and facilitates the formation of the mucin network structure, thereby inhibiting bacterial invasion in the colon to maintain gut homeostasis.

Porphyrin covalent organic nanodisks synthesized using acid-assisted exfoliation for improved bactericidal efficacy.

Porphyrin covalent organic nanodisks (CONs) were synthesized by exfoliating covalent organic frameworks (COFs) in acidic aqueous solutions at pH 4. The synthesized CONs showed remarkable bactericidal activity against Escherichia coli owing to enhanced generation of singlet oxygen upon visible light irradiation.

Fluorescein-Based Type I Supramolecular Photosensitizer via Induction of Charge Separation by Self-Assembly.

Photosensitizers (PSs) are critical substances with considerable potential for use in non-invasive photomedicine. Type I PSs, which generate reactive radical species by electron transfer from the excited state induced via photoirradiation, attracted much attention because of their suitability for photodynamic therapy (PDT) irrespective of the oxygen concentration. However, most organic PSs are type II, which activates only oxygen, generating singlet oxygen (1O2) via energy transfer from the triplet state. Here, we proposed a strategy to form type I supramolecular PSs (SPSs) utilizing the charge-separated state induced by self-assembly. This was demonstrated using a supramolecular assembly of fluorescein, which is a type II PS in the monomeric state; however, it changes to a type I SPS via self-assembly. The switching mechanism from type II to I via self-assembly was clarified using photophysical and electrochemical analyses, with the type I SPS exhibiting significant PDT effects on cancer cells. This study provides a promising approach for the development of type I PSs based on supramolecular assemblies.

Visible Light-Induced Regio- and Enantiodifferentiating [2 + 2] Photocycloaddition of 1,4-Naphthoquinones Mediated by Oppositely Coordinating 1,3,2-Oxazaborolidine Chiral Lewis Acid.

A range of asymmetric photochemical transformations using visible light have recently become considerably attractive. Among the various approaches, chiral Lewis acid association to enones for [2 + 2] and ortho photocycloadditions and oxadi-π-methane rearrangements have shown to be very promising. Naturally, chiral Lewis acid coordination protects one of the prochiral faces of the C═C double bond, which enables an effective enantiodifferentiation in the following bond-forming process(es). Here, we studied regio- and enantiodifferentiating [2 + 2] photocycloaddition reactions of naphthoquinone derivatives mediated by chiral oxazaborolidines. A stereochemical control was quite challenging for the 2-ene-1,4-dione substrate, as a double coordination of Lewis acid essentially cancels out the face selectivity, and a mono-coordination to each carbonyl group leads to an opposite stereochemical outcome. Furthermore, a stepwise coordination in the ground state of Lewis acid in a 1:1 fashion was practically inaccessible. We found that the excited-state decomplexation is a key to accomplish high regio- and enantioselectivities in the photocycloaddition of an ene-dione.

2-O-Methylated ß-Cyclodextrin as an Effective Building Block to Construct Supramolecular Assemblies with Various Morphologies and Molecular Arrangements.

The preparation of supramolecular cyclodextrin (CD) assemblies and control of their assembly mode through guest inclusion in CD cavities have been actively studied. Contrarily, there are limited reports on the control of the assembly mode of guest-free CD molecules by external stimuli. Herein, we report the use of 2-O-methylated ß-cyclodextrin (2-Me-ß-CD) as an effective building block in fabricating supramolecular assemblies with diverse morphologies and molecular arrangements through assembly mode control by various stimuli, such as temperature and solvent. When methanol and diethyl carbonate were used as good and poor solvents, respectively, 2-Me-ß-CD formed an amorphous assembly through solvent evaporation on a polyethylene terephthalate (PET) substrate. Increasing the drying temperature and using crystalline substrates, such as highly oriented pyrolytic graphite (HOPG) and sapphire, changed the assembly mode of 2-Me-ß-CD to a head-to-tail channel assembly. However, when a 2-Me-ß-CD/1-propanol solution was mixed with linear alkanes as a poor solvent, 2-Me-ß-CD with head-to-head channel assembly was formed as a precipitate. Additionally, when the corresponding cyclic alkane was used as an alternative poor solvent, an organogel composed of 2-Me-ß-CD with head-to-head channel assemblies was obtained. The organogel obtained became a precipitate composed of 2-Me-ß-CD with cage-type assembly upon heating at 50 °C. Among the supramolecular assemblies fabricated in this study, the head-to-tail channel assembly is a rare molecular assembly of ß-CD and its derivatives. It possesses a modified columnar cavity that has potential applications in molecular recognition and sensing.

Highly Regulated Supramolecular Assembly of 2-O-Methylated α-Cyclodextrin to Construct Vertically Oriented Microrods on Graphite.

Precisely controlling self-assembled molecules to fabricate highly ordered nano/microstructures is a challenging task. Here, a simple precipitation technique with common solvents forms supramolecular microstructures with highly regulated molecular arrangements from a methylated derivative of α-cyclodextrin at the 2-O position (2-Me-α-CD). The formation of a head-to-tail channel assembly of 2-Me-α-CD through host-guest complexation with a solvent molecule such as benzene or cyclohexane yields well-defined hexagonal microrods. Specifically, the self-assembly of 2-Me-α-CD forms vertically aligned hexagonal microrods on a highly ordered pyrolytic graphite (HOPG) surface via epitaxial growth. This work should provide insight into the design of supramolecular building blocks for controlled self-assembly.

Cyclodextrins with Multiple Pyrenyl Groups: An Approach to Organic Molecules Exhibiting Bright Excimer Circularly Polarized Luminescence.

We report a simple and effective approach to organic molecules exhibiting bright circularly polarized luminescence (CPL) by combining a chiral cyclic molecular scaffold and multiple excimer-enabling moieties. An α-cyclodextrin (CyD) scaffold was modified with six pyrenyl groups to obtain pyrene-cyclodextrins (PCDs) in a one-step synthesis from commercially available compounds. The PCDs exhibited high molar extinction coefficients (ϵ≈105  M-1  cm-1 ), polarized emission with a good dissymmetry factor (|glum |≈10-2 ), and quantum yield (Φf ≈0.5). Owing to the excellent photophysical properties of the PCDs, the circularly polarized luminescence brightness (BCPL ) reached 340 M-1  cm-1 . Photophysical and chiroptical studies of the PCDs with only five pyrene units and with linkers of various lengths connecting the CyD with the pyrene units revealed that the formation of a pyrene excimer in a spatially crowded environment is crucial for CPL anisotropy. This study paves the way for the development of bright CPL organic molecules.

A cyanine dye based supramolecular photosensitizer enabling visible-light-driven organic reaction in water.

We report the aggregation-induced photosensitizing activity of a cyanine dye in water and the mechanism. In addition, using the supramolecular assembly, visible-light-driven photooxidation of hydrophobic aromatic compounds in water was successfully performed.

Terminal Trialkylsilyl Substituent Effect of Janus-type Molecular Tubes on the Inclusion of Unsaturated Fatty Acid Esters.

A new Janus-type cyclodextrin (CD) molecular tube bearing seven triisopropylsilyl (TIPS) groups at one end is synthesized from a heptakis(6-O-triisopropylsilyl)-ß-cyclodextrin (TIPS-ß-CD) dimer possessing multiple linkers through the selective removal of seven TIPS groups at the other end. This Janus-type CD tube exhibits a selective inclusion ability for a cis-fatty acid ester over the corresponding trans-fatty acid ester. In addition, the CD tube shows a twofold higher inclusion ability for unsaturated fatty acid esters than the corresponding CD tube bearing seven tert-butyldimethylsilyl (TBDMS) groups, indicating that the molecular size of the terminal substituents remarkably affects the inclusion ability of the CD tube.

Control of Guest Inclusion and Chiral Recognition Ability of 6-O-Modified ß-Cyclodextrins in Organic Solvents by Aromatic Substituents at the 2-O Position.

The host-guest chemistry and applications of cyclodextrins in aqueous media is well established. However, a comprehensive study in organic solvents is lacking. Here, we report the design and synthesis of 6-O-tert-butyldimethylsilylated ß-cyclodextrin (TBDMS-ß-CD) bearing various aromatic substitutions at the 2-O position and their inclusion complex formation with aromatic guests in nonpolar organic solvents. Compared to the parent TBDMS-ß-CD, these derivatives exhibit at least a 10-fold increase in inclusion ability toward pyrene through cooperative guest binding with the CD cavity and the aromatic substituents at the 2-O position. The type of the aromatic substituent largely affects the chiral recognition ability of TBDMS-ß-CD toward 1-(1-naphthyl)ethylamine in cyclohexane. A TBDMS-ß-CD derivative with a p-tolyl substituent has a remarkable chiral selectivity for the (S)-1-(1-naphthyl)ethylamine over the corresponding (R)-isomer (KS /KR =4.1±0.5), whereas a TBDMS-ß-CD derivative with a 2-picolyl substituent shows the inverse chiral selectivity (KR /KS =8.7±0.6).

Supramolecular organogel formation through three-dimensional α-cyclodextrin nanostructures: solvent chirality-selective organogel formation.

Novel supramolecular organogels were efficiently formed by mixing a 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) solution of α-cyclodextrin (α-CD) with 1- or 2-butanol via the formation of three-dimensional hexagonal nanostructures composed of head-to-tail α-CD channel assemblies. Mixing (R)- and (S)-2-butanol with an α-CD/HFIP solution realized (S)-2-butanol-selective organogel formation.

A novel molecular tube fully modified at one end: selective inclusion of cis-unsaturated fatty acid esters.

A novel cyclodextrin molecular tube with one fully modified and one unmodified end was facilely synthesized by selective desilylation of a 6-O-tert-butyldimethylsilylated ß-cyclodextrin dimer possessing multiple linkers. This molecular tube showed a selective inclusion ability toward cis-unsaturated fatty acid esters by utilizing the asymmetric cylindrical nanocavity.

Aggregation-induced photocatalytic activity and efficient photocatalytic hydrogen evolution of amphiphilic rhodamines in water.

The development of photocatalysts is an essential task for clean energy generation and establishing a sustainable society. This paper describes the aggregation-induced photocatalytic activity (AI-PCA) of amphiphilic rhodamines and photocatalytic functions of the supramolecular assemblies. The supramolecular assemblies consisting of amphiphilic rhodamines with octadecyl alkyl chains exhibited significant photocatalytic activity under visible light irradiation in water, while the corresponding monomeric rhodamines did not exhibit photocatalytic activity. The studies on the photocatalytic mechanism by spectroscopic and microscopic analyses clearly demonstrated the AI-PCA of the rhodamines. Moreover, the supramolecular assemblies of the rhodamines exhibited excellent photocatalytic hydrogen evolution rates (up to 5.9 mmol g-1 h-1).

Comparison of Japanese and Indian intestinal microbiota shows diet-dependent interaction between bacteria and fungi.

The bacterial species living in the gut mediate many aspects of biological processes such as nutrition and activation of adaptive immunity. In addition, commensal fungi residing in the intestine also influence host health. Although the interaction of bacterium and fungus has been shown, its precise mechanism during colonization of the human intestine remains largely unknown. Here, we show interaction between bacterial and fungal species for utilization of dietary components driving their efficient growth in the intestine. Next generation sequencing of fecal samples from Japanese and Indian adults revealed differential patterns of bacterial and fungal composition. In particular, Indians, who consume more plant polysaccharides than Japanese, harbored increased numbers of Prevotella and Candida. Candida spp. showed strong growth responses to the plant polysaccharide arabinoxylan in vitro. Furthermore, the culture supernatants of Candida spp. grown with arabinoxylan promoted rapid proliferation of Prevotella copri. Arabinose was identified as a potential growth-inducing factor in the Candida culture supernatants. Candida spp. exhibited a growth response to xylose, but not to arabinose, whereas P. copri proliferated in response to both xylose and arabinose. Candida spp., but not P. copri, colonized the intestine of germ-free mice. However, P. copri successfully colonized mouse intestine already harboring Candida. These findings demonstrate a proof of concept that fungal members of gut microbiota can facilitate a colonization of the intestine by their bacterial counterparts, potentially mediated by a dietary metabolite.

Fabrication of supramolecular cyclodextrin-fullerene nonwovens by electrospinning.

Direct electrospinning of small molecules has great potential to fabricate a new class of fiber materials because this approach realizes the creation of various functional materials through the numerous molecular combinations. In this paper, we demonstrate a proof-of-concept to fabricate supramolecular fiber materials composed of cyclodextrin (CD)-fullerene inclusion complexes by electrospinning. Similar to the molecular state of fullerenes in solution, the resulting fibers include molecularly-dispersed fullerenes. We believe such a concept could be expanded to diverse host-guest complexes, opening up supramolecular solid materials science and engineering.

GPR31-dependent dendrite protrusion of intestinal CX3CR1+ cells by bacterial metabolites.

Small intestinal mononuclear cells that express CX3CR1 (CX3CR1+ cells) regulate immune responses1-5. CX3CR1+ cells take up luminal antigens by protruding their dendrites into the lumen1-4,6. However, it remains unclear how dendrite protrusion by CX3CR1+ cells is induced in the intestine. Here we show in mice that the bacterial metabolites pyruvic acid and lactic acid induce dendrite protrusion via GPR31 in CX3CR1+ cells. Mice that lack GPR31, which was highly and selectively expressed in intestinal CX3CR1+ cells, showed defective dendrite protrusions of CX3CR1+ cells in the small intestine. A methanol-soluble fraction of the small intestinal contents of specific-pathogen-free mice, but not germ-free mice, induced dendrite extension of intestinal CX3CR1+ cells in vitro. We purified a GPR31-activating fraction, and identified lactic acid. Both lactic acid and pyruvic acid induced dendrite extension of CX3CR1+ cells of wild-type mice, but not of Gpr31b-/- mice. Oral administration of lactate and pyruvate enhanced dendrite protrusion of CX3CR1+ cells in the small intestine of wild-type mice, but not in that of Gpr31b-/- mice. Furthermore, wild-type mice treated with lactate or pyruvate showed an enhanced immune response and high resistance to intestinal Salmonella infection. These findings demonstrate that lactate and pyruvate, which are produced in the intestinal lumen in a bacteria-dependent manner, contribute to enhanced immune responses by inducing GPR31-mediated dendrite protrusion of intestinal CX3CR1+ cells.