Linkage-Editing Pseudo-Glycans: A Reductive α-Fluorovinyl--Glycosylation Strategy to Create Glycan Analogs with Altered Biological Activities.

The acetal (-glycoside) bonds of glycans and glycoconjugates are chemically and biologically vulnerable, and therefore -glycosides are of interest as more stable analogs. We hypothesized that, if the -glycoside linkage plays a vital role in glycan function, the biological activities of -glycoside analogs would vary depending on their substituents. Based on this idea, we adopted a "linkage-editing strategy" for the creation of glycan analogs (pseudo-glycans).

Photoisomerization of "Partially Embedded Dihydropyridazine" with a Helical Structure.

Invited for the cover of this issue are the groups of Kazuteru Usui and Satoru Karasawa at Showa Pharmaceutical University and Yasuhiro Kobori of Kobe University. The image depicts chirality control of helical compounds through cycles of photocleavage and recombination under sunlight with a "Jack and the Beanstalk" motif. Read the full text of the article at 10.

Quantitative and Nondestructive Colorimetric Amine Detection Method for the Solid-Phase Peptide Synthesis as an Alternative to the Kaiser Test.

Solid-phase peptide synthesis (SPPS) is an essential technique for the synthesis of peptide. For half a century, many amine detection methods have been developed to monitor coupling reactions during SPPS. Despite such efforts, to the best of our knowledge, a nondestructive and quantitative colorimetric method has not been developed.

Photoisomerization of "Partially Embedded Dihydropyridazine" with a Helical Structure.

Herein, we report the synthesis of two "partially embedded fused-dihydropyridazine N-aryl aza[5]helicene derivatives" (PDHs) and the demonstration of their intrinsic photo-triggered multi-functional properties based on a Kekulé biradical structure. Introducing bulky electron-withdrawing trifluoromethyl or pentafluoroethyl groups into the aza[5]helicene framework (PDH-CF and -C F ) gives PDH axial chirality based on the helicity of the P and M forms, even at room temperature. Upon photo-irradiation of PDH-CF in a frozen solution, an ESR signal from the triplet biradical with zero-field splitting values, generated by N-N bond dissociation, was observed.

Naphthyridine-Based Electron Push-Pull-Type Amine-Reactive Fluorescent Probe for Sensing Amines and Proteins in Aqueous Media.

In bioengineering, fluorescent amine-reactive probes are invaluable for the detection of amine species. In particular, targeting probes for lysine, which has a free amino group in amino acids, are a valid method for protein detection. For this purpose, many fluorescent "turn-on type" probes with amine reactivity have been developed; however, they require improvements.

Oxidation of an Internal-Edge-Substituted [5]Helicene-Derived Phosphine Synchronously Enhances Circularly Polarized Luminescence.

Invited for the cover of this issue are the groups of Kazuteru Usui and Satoru Karasawa at Showa Pharmaceutical University, and Yoshitane Imai at Kindai University. The image depicts how a phosphine-oxide-bearing helicene exhibits markedly enhanced CPL response in the excited state compared with that of one with a corresponding phosphine. Read the full text of the article at 10.

Chelate-free "turn-on"-type fluorescence detection of trivalent metal ions.

Trivalent metal ions are essential elements in materials and life sciences. To date, fluorescence is the gold standard for the detection of trivalent metal ions, which form a complex with fluorescent chelate ligands (Lewis base type). In this study, we report pH-responsive fluorescent probes for the selective detection of trivalent metal ions that utilize a new chelate-free approach using Brønsted base-type probes.

Oxidation of an Internal-Edge-Substituted [5]Helicene-Derived Phosphine Synchronously Enhances Circularly Polarized Luminescence.

Small chiral organic molecules with CD properties are in high demanded due to their potential use in promising electronic and biological applications. Herein, we reveal a system in which the oxidation of a phosphino group to the corresponding phosphine oxide on the inner rim of a helicene derivative induces a CPL response. Laterally π-extended 7,8-dihydro[5]helicenes bearing phosphine and phosphine oxide groups on their inner helical rims (i.

Acid responsiveness of emissive morpholinyl aminoquinolines and their use for cell fluorescence imaging.

Herein, we report emissive aminoquinoline derivatives (TFMAQ) containing alkylmorpholine and arylmorpholine groups and their photophysical properties, acid-responsiveness, and organelle targeting. The alkylmorpholine group is well-known to favour accumulation in lysosomes and be acid-responsive, but, counterintuitively, the TFMAQ derivatives containing ethylmorpholine groups showed limited accumulation in lysosomes and, instead, preferential accumulation in lipid droplets. The findings reported here will aid the development of organelle/tissue specific dyes for cell imaging and diagnosis.

Harringtonine Ester Derivatives with Enhanced Antiproliferative Activities against HL-60 and HeLa Cells.

Harringtonine (HT), produced from species, is known to exhibit potent antiproliferative activity against myeloid leukemia cells by inhibiting protein synthesis. A previous study using acute promyelocytic leukemia (HL-60) cells raised the possibility that the C-5' methyl group of HT plays an important role in regulating leukemia cell line antiproliferative activity. In order to investigate the effect of hydrocarbon chains at C-5' on the resultant activity, the C-5' methyl group was replaced with various straight- and branched-chain hydrocarbons using the corresponding alcohols, and their antiproliferative activity against HL-60 and HeLa cells was investigated.

Effect of Alkynyl Group on Reactivity in Photoaffinity Labeling with 2-Thienyl-Substituted α-Ketoamide.

Minimalist photo-reactive probes, which consist of a photo-reactive group and a tag for detection of target proteins, are useful tools in chemical biology. Although several diazirine-based and aryl azide-based minimalist probes are available, no keto-based minimalist probe has yet been reported. Here we describe minimalist probes based on a 2-thienyl-substituted α-ketoamide bearing an alkyne group on the thiophene ring.

Helical Oligophenylene Linked with [2.2]Paracyclophane: Stereogenic π-Conjugated Dye for Highly Emissive Chiroptical Properties.

A stereogenic π-system based on dimer (2) and trimer (3) of [2.2]paracyclophane (PC) and biphenyl was prepared and its structural, photophysical, and chiroptical properties were investigated. X-ray analysis revealed that the quaterphenyl moieties in 2 adopt a double helical structure anchoring [2.

A multicolor and ratiometric fluorescent sensing platform for metal ions based on arene-metal-ion contact.

Despite continuous and active development of fluorescent metal-ion probes, their molecular design for ratiometric detection is restricted by the limited choice of available sensing mechanisms. Here we present a multicolor and ratiometric fluorescent sensing platform for metal ions based on the interaction between the metal ion and the aromatic ring of a fluorophore (arene-metal-ion, AM, coordination). Our molecular design provided the probes possessing a 1,9-bis(2'-pyridyl)-2,5,8-triazanonane as a flexible metal ion binding unit attached to a tricyclic fluorophore.

β-Glycosyl Trifluoroborates as Precursors for Direct α-C-Glycosylation: Synthesis of 2-Deoxy-α--glycosides.

-Glycosides are metabolically stable mimics of natural -glycosides and are expected to be useful tools for investigation of the biological functions of glycans. Here, we describe the synthesis of a series of aryl and vinyl -glycosides by stereoinvertive sp-sp cross-coupling reactions of 2-deoxyglycosyl boronic acid derivatives with aryl or vinyl halide, mediated by a photoredox/nickel dual catalytic system. Hydrogenation of the vinyl -glycosides afforded C-linked 2'-deoxydisaccharide analogues.

Characterization of Push-Pull-Type Benzo[X]quinoline Derivatives (X = or ): Environmentally Responsive Fluorescent Dyes with Multiple Functions.

Benzo[X]quinoline (X = or : ) derivatives bearing bis-trifluoromethyl and amine groups have been designed as push-pull-type fluorescent dyes. Through the synthesis of derivatives from 2,7-diaminonaphthalene, linear-type () and angular-type () structural isomers were obtained. X-ray structures of single crystals from six given derivatives revealed that the and series adopt planar- and bowl-shaped structures.

Push-Pull Bisnaphthyridylamine Supramolecular Nanoparticles: Polarity-Induced Aggregation and Crystallization-Induced Emission Enhancement and Fluorescence Resonance Energy Transfer.

Emissive push-pull-type bisnaphthyridylamine derivatives (BNA-X: X=Me, Et, Bzl, Ph, BuBr, and BuTEMPO) aggregate in aqueous methanol. Furthermore, a two-step emission and aggregation process is controllable by varying the methanol-to-water ratio. At 2:3 MeOH/H O, crystallization-induced emission enhancement (CIEE) occurs via formation of an emissive crystal phase, whereas, at 1:9 MeOH/H O, aggregation-induced emission enhancement (AIEE) occurs, induced by emissive supramolecular nanoparticles (NPs).

Characterization and Water-Proton Longitudinal Relaxivities of Liposome-Type Radical Nanoparticles Prepared via a Supramolecular Approach.

For the construction of metal-free magnetic resonance imaging (MRI) contrast agents, radical-based nanoparticles () are promising materials because they allow the water-proton longitudinal relaxivity () to be enhanced not only by paramagnetic resonance effects but also by prolonging the rotational correlation times (τ). However, the τ effect is limited because the radical units are often located within the central hydrophobic core of oil-in-water (o/w) emulsions, resulting in a lack of water molecules surrounding the radical units. In this study, to construct supramolecular that have high values, we designed a liposome-type in which the radical units are located at positions with sufficient surrounding water molecules.

Synthesis of CH-linked α-galactosylceramide and its glucose analogues through glycosyl radical-mediated direct C-glycosylation.

We describe a new synthetic approach for C-linked glycolipid analogues, in which the cleavable O-glycosidic linkage is replaced by a carbon unit. Direct C-glycosylation of a conformationally constrained and stable C1-sp hybridized xanthate carbohydrate with carefully designed sphingosine units afforded the CH-linked analogue of antitumor-active KRN7000 and its glucose congener.

Effects of Substituents on the Properties of Metal-Free MRI Contrast Agents.

Materials possessing electron spin can shorten the relaxation times in magnetic resonance imaging (MRI). For example, gadolinium (Gd) complexes with seven f-orbital electrons are widely used as contrast agents in clinical applications. However, Gd has severe potential side effects, and thus metal-free alternatives are needed.

Photophysical Properties of Emissive Pyrido[3,2-c]carbazole Derivatives and Apoptosis Induction: Development towards Theranostic Agents in Response to Light Stimulus.

Pyridocarbazole moieties are present in many natural products, such as olivacine and ellipticine, and their derivatives are well-known anticancer agents. To develop functional therapeutic and diagnostic compounds, three emissive pyrido[3,2-c]carbazole derivatives, PC-X, containing secondary or tertiary amine groups, were synthesized from an aminoquinoline derivative using a palladium complex as the catalyst. X-ray diffraction analyses revealed that PC-X showed highly planar structures between the pyridine ring and the carbazole framework, exhibiting high fluorescence intensities along with solvatochromic behavior.

Fluorescence Properties and Exciplex Formation of Emissive Naphthyridine Derivatives: Application as Sensors for Amines.

Water-soluble donor-acceptor-type fluorophore 15Nap-Cl having two trifluoromethyl groups and a Cl group on a 1,5-aminonaphthyridine framework was prepared. Fluorophore 15Nap-Cl showed strong solvatochromic fluorescence, and, as the solvent polarity increased, a bathochromic shift was observed accompanied by an increase in the fluorescence quantum yield. In addition, in the presence of amines such as ethylamine, diethylamine, and aniline, further considerable bathochromic shifts in the fluorescence were observed.

Development of Turn-On Probes for Acids Triggered by Aromaticity Enhancement Using Tricyclic Amidine Derivatives.

Two fluorophores consisting of tricyclic amidine derivatives (DHIm and DHPy) were prepared as selective turn-on probes for acids, which were triggered by an aromaticity enhancement. Both amidine derivatives were expanded rings prepared by condensed reactions between the corresponding dibromoalkanes and an aminonaphthyridine analogue. In X-ray analyses, DHIm, in which the dihydroimidazole ring was condensed into aminonaphthyridine, showed high planarity, compared to DHPy, with condensed dihydropyrimidine.

Synthesis of CH-Linked α(1,6)-Disaccharide Analogues by α-Selective Radical Coupling C-Glycosylation.

C-Linked carbohydrate structure, in which the cleavable O-glycosidic linkage is replaced by a carbon unit, is a useful tool for functional analyses of glycoconjugates. We describe a synthetic method for α-CH-linked disaccharide structures, such as Glc(1,6)-Glc, by stereoselective radical-coupling C-glycosylation between a conformationally constrained and stable C1-sp hybridized xanthate donor and a carefully designed acceptor.

Internal-Edge-Substituted Coumarin-Fused [6]Helicenes: Asymmetric Synthesis, Structural Features, and Control of Self-Assembly.

π-Conjugated helicenes containing heteroatoms have attracted significant attention due to their diverse chemical and electronic structures, as well as tunable physical properties. It was rationally anticipated that the self-assembly of coumarin-fused helicenes would be controlled by the effects of a substituent on the internal edge of the helix. Here, this work reports the efficient syntheses of coumarin-fused helicenes 1 a,b (R=Ph, Me), and the enantioselective synthesis of 1 a (R=Ph) by chiral Au -catalyzed hydroarylation.

Thienyl-Substituted α-Ketoamide: A Less Hydrophobic Reactive Group for Photo-Affinity Labeling.

Photoaffinity labeling (PAL) is an important tool in chemical biology research, but application of α-ketoamides for PAL has been hampered by their photoinstability. Here, we show that 2-thienyl-substituted α-ketoamide is a superior photoreactive group for PAL. Studies with a series of synthetic mannose-conjugated α-ketoamides revealed that 2-thienyl substitution of α-ketoamide decreased the electrophilicity of the keto group and reduced the rate of photodegradation.