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Al exists naturally in the environment and is an important component in acidic soils, which harm almost all plants. Furthermore, Al is widely used in food additives, cosmetics, and medicines, resulting in living organisms ingesting traces of Al orally or dermally every day. Accordingly, Al accumulates in the body, which can cause negative bioeffects and diseases, and this concern is gaining increasing attention. Therefore, to detect and track Al in the environment and in living organisms, the development of novel Al-selective probes that are water-soluble and exhibit fluorescence at long wavelengths is necessary. In this study, an Al3+-selective fluorescent probe PSP based on a novel pyrone molecule was synthesized and characterized to detect and track Al in biological systems. PSP exhibited fluorescence enhancement at 580 nm in the presence of Al3+ in aqueous media. Binding analysis using Job's plot and structural analysis using 1H NMR showed that PSP formed a 1:1 complex with Al3+ at the two carbonyl groups of the dimethyl malonate of the pyrone ring. Upon testing in biological systems, PSP showed good cell membrane permeability, detected intracellular Al3+ in human breast cancer cells (MDA-MB-231), and successfully imaged accumulated Al3+ in Microcystis aeruginosa and the larvae of Rheocricotopus species. The novel Al3+-selective fluorescent probe PSP is highly effective and is expected to aid in elucidating the role of Al3+ in the environment and living organisms. [Display omitted] • Water-soluble fluorescent Al3+ probe PSP developed based on phenylsulfonyl-2-pyrone • PSP exhibited fluorescence enhancement toward Al3+ at 580 nm in aqueous media • PSP successfully detected accumulated Al3+ in breast cells and small aquatic organisms [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]

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]

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]

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]

Abstract: The development of a water-soluble and small molecular weight fluorescent probe, 3-(4-methoxyphenyl)-4-(methylsulfanyl)-6-(pyridin-2-yl)pyridin-2(1H)-one (3), for detecting Zn2+ based on pyridine–pyridone skeleton is reported. We observed a clear chelation enhanced fluorescence effect of 3 in the presence of Zn2+. Other fluorescent properties of 3 are discussed. [ABSTRACT FROM AUTHOR]

Abstract: Polysubstituted pyridine derivatives were synthesized by the reaction of ketene dithioacetal, 3,3-bis(methylsulfanyl)methylenemalononitrile 1b, with a variety of active methylene compounds in the presence of either sodium hydroxide or potassium hydroxide as a base in DMSO. This reaction was carried out under economical one-pot reaction conditions (cheap catalyst and solvent) and solved the problem of the odor of methanethiol, commonly derived from reactions of ketene dithioacetals. This is a significant enhancement of GSC (green and sustainable chemistry) in the field of ketene dithioacetal chemistry. [Copyright &y& Elsevier]

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]

The original version of this article unfortunately contained a mistake. The equation under "Experimental -- Spectroscopic Studies" section should be corrected as per the following. [ABSTRACT FROM AUTHOR]

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]

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: A combined experimental and computational study was performed for the spectroscopic properties of novel 2(1H)-pyridones. The compounds were found to be virtually non-fluorescence in solution while modestly fluorescent in solid state. The solvent effects on the UV–vis and fluorescence maxima were estimated by means of a series of ab-initio quantum chemical calculations in conjunction with Polarizable Continuum Model (PCM) method. Influence of structural displacements and intermolecular interactions in crystalline state were examined in details on the spectra of two representative compounds by using Fragment Molecular Orbital (FMO) scheme. The FMO pair interaction analysis of the spectra indicate that (1) intermolecular hydrogen bonds provoke bathochromic shifts (2) electrostatic interactions induce hypsochromic shifts (3) crystal packing effects induce hypsochromic shifts in total from the maxima in vacuo. [Copyright &y& Elsevier]

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]

A novel series of heterocycles were obtained through the condensation reaction of 4-methylthiomaleimides with pyrroles and indoles. The newly synthesized compounds exhibit their major electronic absorption peaks ranging 435-504nm in solution at room temperature. Time-dependent density-functional theory (TDDFT) calculations were systematically performed in order to elucidate their structure-color relationships, using a set of exchange-correlation (XC) functionals. The TDDFT computational scheme employing PCM-TDDFT/6-31+G(d,p)//DFT/6-311G(d,p) level of theory gave qualitatively satisfactory results in their λmax predictions. [ABSTRACT FROM AUTHOR]

Abstract: The major electronic absorption features in visible region were computationally investigated for a series of novel N-methylmaleimide derivatives. The newly synthesized compounds through the reaction of indolizines with N-methylmaleimides exhibited their maxima ranging 587–634nm in solution at room temperature. Time dependent density functional theory (TD-DFT) calculations were performed in order to elucidate their structure–color relationship, as well as to assess its performance using a variety of exchange-correlation (XC) functionals and basis sets. 4-(Indolizin-3-yl)-1-methyl-2,5-dioxo-1H-pyrrole-3-carbonitrile (referred to 3a hereafter), a representative of the new compounds, was analyzed in detail on its intramolecular push–pull electronic structure. As a consequence of systematic evaluation of computational strategies for 3a, we found that the theoretical λ max obtained by PCM-TD-DFT/6-31+G(d,p)//DFT/6-311G(2d,2p) level of theory, which was consistently employed throughout this study, has converged within 2nm deviation from λ max of the most elaborated level considered. Among some of the molecules with near-planarity structure, unusual discrepancies between the theoretical and the experimental λ max were observed, which should be attributed to the well-known TD-DFT limitation to describe multi-configurational or charge transfer (CT) excitations. [Copyright &y& Elsevier]

Abstract: This article comprehensively describes the condensation reactions of functionalized maleimides (3-methylthio-2,5-dioxo-1H-pyrroles) with some nucleophilic reagents to afford a series of novel heterocycles, as briefly reported in a previous communication [Tominaga Y, Komiya K, Itonaga S, Yoshioka N, Kataoka S, Sasaki K, et al. Heterocycles 1997;46:41]. The reactions of the functionalized maleimides (5a–c) with N,N-dialkylanilines (6a–d) smoothly proceeded to give the corresponding 3-(4-dialkylamino)phenyl-1-methyl-1H-pyrrole-2,5-diones (7a–i). Cyclic products, the 2H,4H-[1]benzopyrano[3,4-c]pyrrole-1,3,4-triones (10a–c, 12, 13) were also obtained within the same reaction framework, using 3-dialkylaminophenols (6g–j) and resorcinol (6k) as the nucleophilic reagents. Further treatments of (7a,b,h) with Lawesson''s reagent afforded the brilliant blue mono-thiocarbonyls, 4-(4-dialkylamino)phenyl-3-cyano-1-methyl-5-oxo-pyrrole-2-thiones (9a–c). The UV/vis spectral characteristics of the new heterocycles, particularly of the controversial aromatic mono-thiocarbonyl compounds (9a–c), were computationally analyzed by means of semi-empirical and Time Dependent Density Functional Theory (TDDFT) quantum chemistry calculations. [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]

A small extent of endogenous labile zinc is involved in many vital physiological roles in living systems. However, its detailed functions have not been fully elucidated. In this study, we developed a novel biheteroaryl-based low molecular weight fluorescent sensor, 3-(phenylsulfonyl)-pyrazine–pyridone (5b), and applied it for the detection of endogenous labile zinc ions from lung cancer cells during apoptosis. The electron-withdrawing property of the sulfonyl group between the phenyl ring as an electron donor and the pyridone ring as a fluorophore inhibited the intramolecular charge transfer state, and the background fluorescence of the sensor was decreased in aqueous media. From the structure–fluorescence relationship analysis of the substituent effects with/without Zn2+, compound 5b acting as a sensor possessed favorable properties, including a longer emission wavelength, a large Stokes shift (over 100 nm), a large fluorescence enhancement in response to Zn2+ under physical conditions, and good cell membrane permeability in living cells. Fluorescence imaging studies of human lung adenocarcinoma cells (A549) undergoing apoptosis revealed that compound 5b could detect endogenous labile zinc ions. These experiments suggested that the low molecular weight compound 5b is a potential fluorescence sensor for Zn2+ toward understanding its functions in living systems. [ABSTRACT FROM AUTHOR]

The title pyrimidines exhibit blue-green fluorescence in solid state. [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]