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.

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.

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.

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.

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.

1,8-Diphenyl-9,10-Bis(arylethynyl)phenanthrenes: Synthesis, Distorted Structure, and Optical Properties.

The synthesis and optical properties of 1,8-diphenyl-9,10-bis(arylethynyl)phenanthrenes, which are distorted phenanthrenes, are reported. The presence of the two phenyl groups at the 1,8-positions of phenanthrene significantly distorts the molecular geometries, as was evidenced by X-ray crystallography. The congested substitution pattern in the K region results in a distorted aromatic framework, which leads to a redshift in the emission spectrum. These observations are in stark contrast to 9,10-bis(phenylethynyl)phenanthrene with no phenyl groups at the 1,8-positions. A large Stokes shift suggested extensive structural relaxation between the phenyl and arylethynyl units in the excited state, which was supported by theoretical calculations.

Preparation of Pickering emulsions through interfacial adsorption by soft cyclodextrin nanogels.

BACKGROUND: Emulsions stabilized by colloidal particles are known as Pickering emulsions. To date, soft microgel particles as well as inorganic and organic particles have been utilized as Pickering emulsifiers. Although cyclodextrin (CD) works as an attractive emulsion stabilizer through the formation of a CD-oil complex at the oil-water interface, a high concentration of CD is normally required. Our research focuses on an effective Pickering emulsifier based on a soft colloidal CD polymer (CD nanogel) with a unique surface-active property. RESULTS: CD nanogels were prepared by crosslinking heptakis(2,6-di-O-methyl)-ß-cyclodextrin with phenyl diisocyanate and subsequent immersion of the resulting polymer in water. A dynamic light scattering study shows that primary CD nanogels with 30-50 nm diameter assemble into larger CD nanogels with 120 nm diameter by an increase in the concentration of CD nanogel from 0.01 to 0.1 wt %. The CD nanogel has a surface-active property at the air-water interface, which reduces the surface tension of water. The CD nanogel works as an effective Pickering emulsion stabilizer even at a low concentration (0.1 wt %), forming stable oil-in-water emulsions through interfacial adsorption by the CD nanogels. CONCLUSION: Soft CD nanogel particles adsorb at the oil-water interface with an effective coverage by forming a strong interconnected network and form a stable Pickering emulsion. The adsorption property of CD nanogels on the droplet surface has great potential to become new microcapsule building blocks with porous surfaces. These microcapsules may act as stimuli-responsive nanocarriers and nanocontainers.

Cyclodextrin polymers as highly effective adsorbents for removal and recovery of polychlorobiphenyl (PCB) contaminants in insulating oil.

A total of 179 countries (parties) ratified the Stockholm Convention on persistent organic pollutants (POPs) and agreed to destroy polychlorobiphenyls (PCBs) and develop a sound management plan by 2028. Currently, still 3 million tons of PCB-contaminated oil and equipment need to be managed under the Stockholm Convention. Thus, the development of a facile and environmentally benign method to treat large amounts of oil stockpiles contaminated with PCBs is a crucial subject. Herein, we report that cyclodextrin (CD) polymers, which are easily prepared by cross-linking the renewable cyclic oligosaccharide γ-cyclodextrin (γ-CD) with dibasic acid dichlorides, are a new selective and powerful adsorbent to remove PCB contaminants in oil. When PCB (100 ppm)-contaminated oil was passed through a column packed with the terephthaloyl-cross-linked γ-CD polymer (TP-γ-CD polymer) at 80-110 °C, the PCB contaminants were completely removed from the oil. Additionally, methyl esterification of the free carboxylic groups of the TP-γ-CD polymer enabled the complete recovery of the PCBs adsorbed on the polymer (with >99.9% recovery efficiency) by simply washing with acetone. The methyl-esterified TP-γ-CD polymer could be recycled at least 10 times for PCB adsorption without any loss in the adsorption capability. These results revealed that the γ-CD polymers can function as highly effective and powerful adsorbents for the removal and recovery of PCBs from PCB-contaminated oil and, thus, significantly contribute to the protection of the global environment.

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.

Chiral recognition and kinetic resolution of aromatic amines via supramolecular chiral nanocapsules in nonpolar solvents.

Herein we report the first example of chiral recognition and kinetic resolution of aromatic amine guests using supramolecular nanocapsules assembled from cyclodextrin derivatives in nonpolar media. With these nanocapsules, an extremely high chiral recognition of 1-(1-naphthyl)ethylamine (1) in cyclohexane was achieved, with a binding selectivity of up to 41 for (S)-1 over (R)-1. In addition, kinetic resolution of 1 through enantioselective N-acylation was accomplished with an enantiomeric excess of up to 91%.

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.

Involvement of functional groups on the surface of carboxyl group-terminated polyamidoamine dendrimers bearing arbutin in inhibition of Na⁺/glucose cotransporter 1 (SGLT1)-mediated D-glucose uptake.

A carboxyl group-terminated polyamidoamine dendrimer (generation: 3.0) bearing arbutin, which is a substrate of Na⁺/glucose cotransporter 1 (SGLT1), via a nonbiodegradable ω-amino triethylene glycol linker (PAMAM-ARB), inhibits SGLT1-mediated D-glucose uptake, as does phloridzin, which is a typical SGLT1 inhibitor. Here, since our previous research revealed that the activity of arbutin was dramatically improved through conjugation with the dendrimer, we examined the involvement of functional groups on the dendrimer surface in inhibition of SGLT1-mediated D-glucose uptake. PAMAM-ARB, with a 6.25% arbutin content, inhibited in vitro D-glucose uptake most strongly; the inhibitory effect decreased as the arbutin content increased. In vitro experiments using arbutin-free original dendrimers indicated that dendrimer-derived carboxyl groups actively participated in SGLT1 inhibition. However, the inhibitory effect was much less than that of PAMAM-ARB and was equal to that of glucose moiety-free PAMAM-ARB. Data supported that the glucose moiety of arbutin was essential for the high activity of PAMAM-ARB in SGLT1 inhibition. Analysis of the balance of each domain further suggested that carboxyl groups anchored PAMAM-ARB to SGLT1, and the subsequent binding of arbutin-derived glucose moieties to the target sites on SGLT1 resulted in strong inhibition of SGLT1-mediated D-glucose uptake.

Controlled release using a polymer stereocomplex capsule through the selective extraction and incorporation of one capsule shell component.

Isotactic poly(methyl methacrylate) (it-PMMA)/syndiotactic poly(methacrylic acid) (st-PMAA) stereocomplex hollow capsules were fabricated by the deposition of stereocomplex films of it-PMMA and st-PMAA on silica particles by alternate layer-by-layer assembly and the subsequent removal of the silica particles with aqueous HF. The selective extraction of st-PMAA from the it-PMMA/st-PMAA stereocomplex capsule shells was successfully carried out by immersion in a pH 6-9 aqueous solution. The incorporation of st-PMAA into the resulting porous capsule shells was performed by immersion in an acetonitrile/water (1/1) solution of st-PMAA. The controlled release of an encapsulated dye from the it-PMMA/st-PMAA hollow capsules was achieved by combining the selective extraction of st-PMAA from the capsule shells and the incorporation of st-PMAA into the resulting porous shells.

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.

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.

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.