Exploring the Condensation Reaction between Aromatic Nitriles and Amino Thiols To Optimize In Situ Nanoparticle Formation for the Imaging of Proteases and Glycosidases in Cells

The condensation reaction between 6-hydroxy-2-cyanobenzothiazole (CBT) and cysteine has been shown for various applications such as site-specific protein labelling and in vivo cancer imaging. This report further expands the substrate scope of this reaction by varying the substituents on aromatic nitriles and amino thiols and testing their reactivity and ability to form nanoparticles for cell imaging. The structure–activity relationship study leads to the identification of the minimum structural requirement for the macrocyclization and assembly process in forming nanoparticles. One of the scaffolds made of 2-pyrimidinecarbonitrile and cysteine joined by a benzyl linker was applied to design fluorescent probes for imaging caspase-3/7 and β-galactosidase activity in live cells. These results demonstrate the generality of this system for imaging hydrolytic enzymes.     

A validated LC‐MS/MS method for the determination of canagliflozin,a sodium–glucose co‐transporter 2 (SGLT‐2) inhibitor,in a lower volume of rat plasma: application to pharmacokinetic studies in rats

Canagliflozin is a novel, orally selective inhibitor of sodium‐dependent glucose co‐transporter‐2 (SGLT2) for the treatment of patients with type 2 diabetes mellitus. In this study, a validated liquid chromatography–tandem mass spectrometry (LC‐MS/MS) method for the quantitative analysis of canagliflozin in a lower volume of rat plasma (0.1 mL) was established and applied to a pharmacokinetic study in rats. Following liquid–liquid extraction by tert‐butyl methyl ether, chromatographic separation of canagliflozin was performed on a Quicksorb ODS (2.1 mm i.d. × 150 mm, 5 µm size) using acetonitrile–0.1% formic acid (90:10, v/v) as the mobile phase at a flow rate of 0.2 mL/min. The detection was carried out using an API 3200 triple‐quadrupole mass spectrometer operating in the positive electrospray ionization mode. Selected ion monitoring transitions of m/z = 462.0 [M + NH₄]⁺ → 191.0 for canagliflozin and m/z = 451.2 [M + H]⁺ → 71.0 for empagliflozin (internal standard) were obtained. The validation of the method was investigated, and it was found to be of sufficient specificity, accuracy and precision. Canagliflozin in rat plasma was stable under the analytical conditions used. This validated method was successfully applied to assess the pharmacokinetics of canagliflozin in rats using 0.1 mL rat plasma. Copyright © 2016 John Wiley & Sons, Ltd.     

Complexation of acyclic ligands having two terminal quinoline units with alkali metal cations

Abstract

Acyclic multidentate ligands consisting of an oligooxyethylene chain (di-, tri-, tetra-, and penta-) and two terminal rigid quinaldate end groups were newly prepared and their complexation properties with alkali metal cations were estimated by the solvent extraction method to indicate a better affinity for K⁺. Among them, the tetraethylene glycol derivative showed the highest K⁺ binding on about the same level as 18-crown-6. Their conformations in solution and in the solid state were examined by using ¹H- and ¹³C-NMR spectroscopy and X-ray crystal analyses, respectively. The better binding of K⁺ in comparison with the corresponding glymes or analogues having the same donor sites was reasonably explained by considering the effective co-ordination of the carbonyl oxygen of the ester groups and the parallel π-stacking interaction between two quinaldate surfaces.     

Synthesis of Sulfonylurea Derivatives Used as Oral Antidiabetics by the Selenium-Assisted Carbonylation Using Carbon Monoxide with Sulfur

Sulfonylurea derivatives including useful antidiabetics (Tolbutamide, Chlorpropamide) were synthesized in good yields from benzene-sulfonamides with thiocarbamates in the presence of DBU. Thiocarbamates were prepared by the selenium-assisted carbonylation of primary amines with carbon monoxide, sulfur, and methyl iodide under mild conditions.     

One-Step Dialkoxylation of Aromatic Diamines with Trialkyl Phosphate

Alkylesters of orthophosphoric acids have been used for alkylation of phenols¹, anilines², and nitrogen heterocyclic compounds.³ However, no example is reported on their use as an alkoxylating agent for aromatic amines. We have found that alkyl phosphates can act as alkoxylating agents for aromatic diamines in the presence of H₂O or aqueous H₃PO₄. We now report the one-step dialkoxylation of aromatic diamines such as diaminoanthracene and -naphthalene by trialkyl phosphates.     

Induced production of novel prenyldepside and coumarins in endophytic fungi Pestalotiopsis acaciae

Concomitant supplementation of a histone deacetylase inhibitor, suberoylanilide hydroxamic acid, and a DNA methyltransferase inhibitor, 5-azacytidine, to the culture medium of a plant endophytic fungus, Pestalotiopsis acaciae, dramatically altered its metabolic profiles. As a result, three novel aromatic compounds, 2′-hydroxy-6′-hydroxymethyl-4′-methylphenyl-2,6-dihydroxy-3-(2-isopentenyl)benzoate (1), 4,6-dihydroxy-7-hydroxymethyl-3-methylcoumarin (2) and 4,6-dihydroxy-3,7-dimethylcoumarin (3), were isolated, along with five known polyketides, endocrocin (4), pestalotiollide B (5), pestalotiopyrone G (6), scirpyrone A (7) and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (8).     

Nuclear field shift effect in isotope fractionation of thallium

Environmental transport of Tl is affected by redox reaction between Tl(I) and Tl(III) and ligand exchange reactions of them. In order to deepen the knowledge of Tl chemistry, we investigated fractionation of Tl stable isotopes (²⁰³Tl and ²⁰⁵Tl) in a chemical exchange system. Tl isotopes were fractionated in a liquid–liquid extraction system, in which aqueous and organic phases are hydrochloric acid solution and dichloroethane including a crown ether, respectively. After purification by ion-exchange chemistry, the isotope ratio of ²⁰⁵Tl/²⁰³Tl in equilibrated aqueous phase was measured precisely by multiple-collector–inductively-coupled-plasma–mass-spectrometry. A large isotope fractionation >1 ‰ was found. Electronic structures of possible Tl species (hydrated Tl⁺, Tl³⁺, and Tl chlorides) were calculated by ab initio methods, and the isotope fractionation factor was theoretically obtained. The isotope fractionation via intramolecular vibrations was calculated to be much smaller than the experimental result. The isotope fractionation via isotopic change in nuclear volume, named the nuclear field shift effect, was calculated to be >1 ‰ in Tl(I)–Tl(III) redox systems and/or ligand exchange systems of Tl(III). The nuclear field shift effect was found to be the major origin of Tl isotope fractionation.     

Hydrogen-bonded liquid crystals built from hydrogen-bonding donors and acceptors. Infrared study on the stability of the hydrogen bond between carboxylic acid and pyridyl moieties

Abstract

The stability of a hydrogen-bonded complex built through inter-molecular hydrogen bonding between carboxylic acid and pyridine fragments has been examined using infrared spectroscopy. Infrared spectra as a function of temperature have been recorded for the 1:1 complex of 4-hexyloxybenzoic acid and trans-4-propoxy-4′-stilbazole from the crystalline state to the isotropic state. A dependence of the stability of the hydrogen bond on molecular orientation is observed clearly in the infrared spectra. The spectra also suggest that the hydrogen bond is an unionized type with a double minimum potential energy.     

Photochromic chiral liquid crystalline systems containing spiro-oxazine with a chiral substituent I. Synthesis and characterization of compounds

Photochromic acrylates containing both biphenylene and spiro-oxazine moieties with a chiral substituent and the related polymers were prepared and yielded photochromic chiral liquid crystalline systems. The photochromic acrylates containing both an undecamethylene group and a (2S, 3S)-2-chloro-3-methylpentanoyloxy group (A11SOP) or a (-)-menthoxyacetoxy group (A11SOM) gave a supercooled mesophase; the latter reflected right-handed visible light (blue colour) at room temperature. On the other hand, the photochromic acrylate containing both the (R)-(-)-2-methylpropylene and (2S, 3S)-2-chloro-3-methylpentanoyloxy groups (A3SOP) showed no mesophase. The related homopolymers, PA11SOP and PA11SOM, did not exhibit mesophases because of steric hindrance between the side groups of the polymers. However, only PA11SOM exhibited shear-induced birefringence under 100-104°C. Several copolymers consisting of the nematogenic monomer, 4-[4-(6-acryloyloxyhexyloxy)benzoyloxy]benzonitrile (A6CN), and A11SOP or A11SOM possessed a smectic phase due to reduction of the steric hindrance between the potentially smectogenic A11SOP or A11SOM moieties.     

Characterization of flower-inducing compound in Lemna paucicostata exposed to drought stress

A flower-inducing compound, LDS1, was isolated from a free-floating aquatic plant, Lemna paucicostata. The chemical structure and the absolute stereochemistry of LDS1 were determined as (9R,13R,11E,15Z)-9,13-dihydroxy-10-oxooctadeca-11,15-dienoic acid for its most abundant diastereomer. LDS1 was enzymatically produced when the plant was exposed to drought stress, and induced flowering at a concentration of 10 nM.