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The chemical reaction of 2-(methylsulfinyl)naphtho[2,3-d]thiazole-4,9-dione (3) using different amines, including benzylamine (4a), morpholine (4b), thiomorpholine (4c), piperidine (4d), and 4-methylpiperazine (4e), produced corresponding new tricyclic naphtho[2,3-d]thiazole–4,9–dione compounds (5a–e) in moderate-to-good yields. The photophysical properties and antimicrobial activities of these compounds (5a–e) were then characterized. Owing to the extended π-conjugated system of naphtho[2,3-d]thiazole–4,9–dione skeleton and substituent effect, 5a–e showed fluorescence both in solution and in the solid state. The introduction of nitrogen-containing heterocycles at position 2 of the thiazole ring on naphtho[2,3-d]thiazole-4,9-dione led to large bathochromic shifts in solution, and 5b–e exhibited orange-red fluorescence with emission maxima of over 600 nm in highly polar solvents. Staphylococcus aureus (S. aureus) is a highly pathogenic bacterium, and infection with its antimicrobial-resistant pathogen methicillin-resistant S. aureus (MRSA) results in serious clinical problems. In this study, we also investigated the antimicrobial activities of 5a–e against S. aureus, MRSA, and S. epidermidis. Compounds 5c with thiomorpholine group and 5e with 4-methylpiperazine group showed potent antimicrobial activity against these bacteria. These results will lead to the development of new fluorescent dyes with antimicrobial activity in the future. [ABSTRACT FROM AUTHOR]

Multi-substituted conjugated dienes are useful intermediates for the synthesis of various biologically active compounds and functional materials. In this study, one-pot synthesis of multi-substituted 2,4-butadienes was achieved via the reaction of ketene dithioacetal, 3,3-bis(methylsulfanyl)methylenemalononitrile (1), with a variety of aromatic ketone compounds. Complete stereoselective (2Z,4E)-2,4-dienamide (3a) was obtained from 1 with 4-methoxyacetophenone (2a) in the presence of sodium hydroxide as a base in DMSO. Similarly, the reaction of 1 with electron-rich aromatic ketones or heterocyclic aromatic ketones gave (2Z,4E)-2,4-dienamide compounds as the sole product in 31–61 yields. In the proposed synthetic sequence, the process consists of a cascade reaction involving the addition of 1 to ketone compound, elimination of methylthiolate anion from 1, subsequent intramolecular cyclization and ring opening reaction by readdition of methylthiolate anion. Moreover, all the (2Z,4E)-2,4-dienamide compounds (3a–j) obtained in this study exhibited blue-green fluorescence in the solid state, which suggested the possibility of obtaining functional conjugated dienes by this novel one-pot synthetic method. [ABSTRACT FROM AUTHOR]

Fluorescence probes that selectively image cadmium are useful for detecting and tracking the amount of Cd2+ in cells and tissues. In this study, we designed and synthesized a novel Cd2+ fluorescence probe based on the pyridine-pyrimidine structure, 4-(methylsulfanyl)-6-(pyridin-2-yl)pyrimidin-2-amine (3), as a low-molecular-weight fluorescence probe for Cd2+. Compound 3 could successfully discriminate between Cd2+ and Zn2+ and exhibited a highly selective turn-on response toward Cd2+ over biologically related metal ions. The dissociation constant (Kd) and the limit of detection (LOD) of 5.4 × 10− 6 mol L− 1 and 4.4 × 10− 7 mol L− 1, respectively, were calculated using fluorescence titration experiments. Studies with closely related analogs showed that the bis-heterocyclic moiety of 3 acted as both a coordination site for Cd2+ and a fluorophore. Further, the methylsulfanyl group of compound 3 is essential for achieving selective and sensitive Cd2+ detection. Fluorescence microscopy studies using living cells revealed that the cell membrane permeability of compound 3 is sufficient to detect intracellular Cd2+. These results indicate that novel bis-heterocyclic molecule 3 has considerable potential as a fluorescence probe for Cd2+ in biological applications. [ABSTRACT FROM AUTHOR]

A very simple and facile one-pot method for the synthesis of pyrimidine derivatives is presented. In this method, 2-aryl-pyrimidine derivatives were prepared by the reaction of ketene N,S-acetal 1 with commercially available aryl aldehydes by heating under solvent and catalyst-free conditions. The synthesized pyrimidine derivatives showed blue-green fluorescence in solid state. [ABSTRACT FROM AUTHOR]

Novel, low-molecular-weight fluorescent sensors based on a pyridine–pyridone core structure, which functions as both the chelating part moiety for Zn 2+ and as the fluorophore, were investigated. The length of the methylene spacer between the phenyl ring and the 3-position of the pyridone ring greatly influenced the emission wavelength and intensity upon Zn 2+ binding. 5-Benzyl-4-(methylsulfanyl)-[2,2′-bipyridin]-6(1 H )-one ( 2 ) (MW = 308) with a methylene spacer of n = 1 showed good water solubility, a 30 nm bathochromic shift in its emission wavelength and an 18-fold fluorescence enhancement in response to Zn 2+ . In addition, fluorescence microscopy imaging showed that 2 could be used to detect Zn 2+ in living cells. [ABSTRACT FROM AUTHOR]

Zinc is an essential trace element involved in many biological activities; however, its functions are not fully understood. To elucidate the role of endogenous labile Zn2+, we developed a novel ratiometric fluorescence probe, 5-(4-methoxyphenyl)-4-(methylsulfanyl)-[2,2′-bipyridin]-6-amine (6 (rBpyZ)) based on the 6-amino-2,2′-bipyridine scaffold, which acts as both the chelating agent for Zn2+ and the fluorescent moiety. The methoxy group acted as an electron donor, enabling the intramolecular charge transfer state of 6 (rBpyZ), and a ratiometric fluorescence response consisting of a decrease at the emission wavelength of 438 nm and a corresponding increase at the emission wavelength of 465 nm was observed. The ratiometric probe 6 (rBpyZ) exhibited a nanomolar-level dissociation constant (Kd = 0.77 nM), a large Stokes shift (139 nm), and an excellent detection limit (0.10 nM) under physiological conditions. Moreover, fluorescence imaging using A549 human lung adenocarcinoma cells revealed that 6 (rBpyZ) had good cell membrane permeability and could clearly visualize endogenous labile Zn2+. These results suggest that the ratiometric fluorescence probe 6 (rBpyZ) has considerable potential as a valuable tool for understanding the role of Zn2+ in living systems. [ABSTRACT FROM AUTHOR]

Abstract: One-pot synthesis of a new 2-pyrone dye (3a) by the reaction of 4-diethylamino-acetophenone (1) with methyl 2-cyano-3,3-bis(methylsulfanyl)acrylate (2) in the presence of sodium hydroxide as the base was carried out in DMSO. Compound 4a was synthesized by the replacement of methylsulfanyl group of 3a with dimethylamine at 4-position of pyrone ring. Similarly, compound 5a was prepared via the reaction of 3a with diethyl malonate. Compounds 3a–5a exhibited the following fluorescence in the solid state: red (3a), green (4a), and orange (5a). In addition, it was revealed that 2-pyrone dyes exhibit fluorescence in various solvents and show positive solvatochromism. Compounds 3a and 5a exhibited intense fluorescence in chloroform and dichloromethane (fluorescence quantum yield Φ: 0.94–0.95). In contrast, compound 4a exhibited intense fluorescence in polar solvents (methanol: Φ = 0.92). These 2-pyrone dyes have the potential for applications in various fields. [Copyright &y& Elsevier]

A high-affinity and low-molecular-weight fluorescent Zn 2+ sensor 1 based on a 2,2′-bipyridine scaffold, which functions as both the chelating moiety for Zn 2+ and the fluorophore, was developed and evaluated in biological applications. Controlling the occurrence of tautomerism of the chelating moiety for Zn 2+ by introducing an amino group at the 6-position of the pyridine ring dramatically increased the binding affinity toward Zn 2+ . Fluorescent sensor 1 exhibited a nanomolar-range dissociation constant ( K d = 2.2 nM), a large Stokes shift (140 nm), and an 8.6-fold turn-on response to Zn 2+ under physiological conditions. Fluorescence images revealed that fluorescent sensor 1 exhibits good properties with respect to aqueous solubility and cell permeability and can quantitatively detect the Zn 2+ levels in living cells. Furthermore, a 65 Zn 2+ radioactive zinc isotope uptake study revealed the real concentration of accumulated Zn 2+ at the detection limit. The novel fluorescent sensor 1 is a promising sensor for use in biological applications. [ABSTRACT FROM AUTHOR]

Abstract: We report a novel series of fluorescent Zn2+ sensors based on a pyridine–pyridone core structure, which functions as both the chelating part for Zn2+ and as the fluorophore. Pyridine–pyridone derivatives obtained by replacement of an electron-donating group with an electronic-withdrawing group at the 3-position of the pyridone ring showed almost no background fluorescence because electron transfer to the fluorophore was inhibited. However, these derivatives showed strong fluorescence with Zn2+. Coordination with Zn2+ greatly influenced the electron transfer of the fluorophore, and, as a result, enabled fluorescence ON/OFF switching. In these sensors, 4-[4-(methylsulfanyl)-2-oxo-6-(pyridin-2-yl)-1,2-dihydropyridin-3-yl]benzoic acid (5) displayed excellent properties: small molecular weight (MW=338), good water solubility, large Stokes shift (132nm), and fluorescence ON/OFF switching with Zn2+. In addition, fluorescence images of Zn2+ with 5 in living cells show that the new fluorescent sensor is useful for biological applications. [Copyright &y& Elsevier]

Two 2-pyridone tautomeric analogs, methoxypyridine 4 and N -methylpyridone 5 , were synthesized, and their spectroscopic properties were investigated both experimentally and computationally. A detailed photophysical study reveals that 4 shows high fluorescence quantum yields not only in chloroform but also in ethanol, and the strong fluorescence in solution might be attributed to the enol form (pyridine) of the 2-pyridone. Furthermore, we designed and synthesized novel 2-substitued pyridines to achieve more intense emissions in both solution and the solid state. Substituent modification with phenylsulfonyl, morpholino, and 4-diethylamino groups greatly affected the fluorescence properties, and methoxypyridine 7 and morpholinopyridine compound 8 showed fluorescence in various solvents (Ф = 0.59–0.95) and the solid state (Ф = 0.12–0.15). A hypsochromic shift in the emission maximum wavelength and strong fluorescence in the solid state (Ф = 0.39) were observed for dimorpholinopyridine 9. Morpholinopyridine 11 showed intense fluorescence in all nonpolar and polar solvents. Systematic time-dependent density functional theory calculations were performed for the compounds whose electronic and fluorescent maxima were computationally reproduced with good agreement to those from experiment. In detail, the drastic difference in the emission intensity between 4 and 5 in solution was successfully explained using CASSCF calculations, which revealed the presence of conical intersections between the ground and the excited states. • Joint experimental and computational studies of new 2-pyridone tautomeric compounds were performed. • Strong fluorescence in solution is attributed to the enol form of the 2-pyridone. • Methoxypyridine and morpholinopyridines exhibited solid-state fluorescence and a high fluorescence quantum yield in solution. • Fluorescence solvatochromic effects depend on the chemical structure and arrangement of the substituents were observed. [ABSTRACT FROM AUTHOR]

Novel highly emissive 2-pyridone-based compounds 3a,b and 4a–d were synthesized by a convenient one-pot method from 4-(dialkylamino)acetophenones ( 1a , b ) and cyanoketene dithioacetal ( 2a ) or sulfonyl ketene dithioacetals ( 2b , c ), and their fluorescence properties were investigated. A simple structure modification of 2-pyridones significantly affected their optical properties including the emission wavelength and fluorescence intensity. All the 6-(4-dialkylamino)phenyl-2-pyridones showed positive solvatofluorochromism and intense blue-green fluorescence in nonpolar solvents such as chloroform ( Ф : 0.80–0.92) and dichloromethane ( Ф : 0.83–0.94). A hypsochromic shift of the fluorescence emission maxima and strong fluorescence in a polar solvent were observed by substituting the dimethylamino group with a diethylamino group. Introduction of a sulfonyl group disturbed the molecular planarity of compounds 4a , 4b , and 4d , resulting in a strong fluorescence in acetone ( Ф : 0.86–0.95) and acetonitrile ( Ф : 0.59–0.88). These results indicate that 2-pyridone-based compounds have great potential as fluorophores for various practical applications. [ABSTRACT FROM AUTHOR]