Ratiometric sensing of Zn2+ with a new benzothiazole-based fluorescent sensor and living cell imaging.

A new fluorescent probe, 3-(benzo[d]thiazol-2-yl)-5-bromosalicylaldehyde-4N-phenyl thiosemicarbazone (BTT), for ratiometric sensing of Zn2+ ions in methanol/HEPES buffer solution (3 : 2, pH = 7.4) is reported in this paper. The presence of Zn2+ ions yields a significant blue shift in the maximum emission of BTT from 570 nm to 488 nm, accompanied by a clear color change from orange to green. This emission change of BTT upon binding to Zn2+ in a 1 : 1 ratio may be due to the block of excited state intramolecular proton transfer (ESIPT) as well as chelation enhanced fluorescence (CHEF) on complex formation. The limit of detection (LOD) determined for Zn2+ quantitation was down to 37.7 nM. In addition, the probe BTT displays the ability to image both exogenous Zn2+ ions loaded into HeLa cells and endogenous Zn2+ distribution in living SH-SY5Y neuroblastoma cells.

Formal enantioselective total synthesis of bisdehydroneostemoninine.

A formal enantioselective total synthesis of bisdehydroneostemoninine employing L-glutamic acid as the chiral pool is described. The key features of the synthesis include regioselective and enantioselective opening the chiral epoxide with dimethylsulfonium methylide and tandem Friedel-Crafts cyclization followed by lactonization to form the 5-7-5 tricyclic core of the target stemona alkaloids. The synthetic route provides opportunities to explore the biological behavior of enantiopure bisdehydroneostemoninine. [Formula: see text].

The biochemical effect of Ser166 phosphorylation on Euplotes octocarinatus centrin.

Centrin is a member of the EF-hand superfamily that is phosphorylated during mitosis and is associated with alterations of contractile fibers. To obtain insight into the structural basis for the functional effects of phosphorylation, we found that the serine residue at position 166 of Euplotes octocarinatus centrin (EoCen) can be phosphorylated by protein kinase A (PKA) in the absence or presence of metal ions using (31)P-NMR spectroscopy. Cations of Ca(2+) and Tb(3+) bound to EoCen resulted in an important structural transition from a closed to an open state. EoCen in both the closed and the open state can be phosphorylated by PKA. After phosphorylation, secondary and tertiary structural changes of EoCen, mainly on its C-terminal domain (C-EoCen), were noted through circular dichroism spectroscopy, native polyacrylamide gel electrophoresis, and 2-p-toluidinylnaphthalene-6-sulfonate fluorescence. After the protein was phosphorylated, the α-helix content and the extent of the exposed hydrophobic surface on EoCen were decreased. Phosphorylated EoCen has higher affinity for the peptide melittin than nonphosphorylated EoCen. In addition, binding of melittin with phosphorylated C-EoCen was enthalpy-driven.

Ultraviolet-visible light (UV-Vis)-reversible but fluorescence-irreversible chemosensor for copper in water and its application in living cells.

An ultraviolet-visible light (UV-Vis)-reversible but fluorescence-irreversible chemosensor was developed for the detection of copper. Coordination between the probe, 2-pyridylaldehyde fluorescein hydrazone (FHP), and Cu(2+) gave a reversible UV-Vis response, Storage of the probe-Cu complex resulted in hydrolytic cleavage of the N═C bond, which released the fluorophore (ring-opened fluorescein hydrazine) and gave irreversible fluorescence. Thus, FHP becomes a multifunctional chemosensor, and its reversibility can be controlled by the reaction time. Cu(2+) in living cells could be detected using FHP and general fluorescence methods.

A phenazine-imidazole based ratiometric fluorescent probe for Cd2+ ions and its application in in vivo imaging.

A new phenazine-imidazole based Schiff base (PIS) fluorescent probe has been developed for the ratiometric detection of Cd2+ ions in aqueous media at physiological pH. PIS upon binding with Cd2+ ions shows red shifted fluorescence and thereby, permits ratiometric detection of Cd(II) ions. A detection limit down to 2.10 × 10-8 M was determined for Cd2+ quantitation. Also, the accompanying apparent fluorescence color change (from yellow to orange red) is noticeable to the naked eye under a UV-lamp. The sensing mechanism could be attributed to the 1 : 1 PIS-Cd complexation, followed by extension of the conjugation due to better planarity and modulation of the charge transfer efficiency in the probe. This was complemented by solvatochromism and density functional theory calculations. Furthermore, PIS was used to detect Cd2+ in Oxya chinensis cells, zebrafish larvae and live tissues of Arabidopsis thaliana under a fluorescence microscope, showing great potential in analyzing living biosystems.

Palladium-Catalyzed Regioselective Coupling Cyclohexenone into Indoles: Atom-Economic Synthesis of ß-Indolyl Cyclohexenones and Derivatization Applications.

Herein, we report a palladium-catalyzed dehydrogenative cross-coupling of indoles with cyclic enones to give ß-indolyl cyclic enones under mild and neutral reaction conditions. The key to the success is to explore a mild condition, which ensures the indole C-H activation and subsequent syn ß-hydride elimination through rapid enolization isomerization of Pd(II)-enolate while suppressing other undesired side reactions. Synthetic utility has also been demonstrated in the flexible transformation of the coupling products to meta-phenols and benzo[a]carbazoles.

New colorimetric and fluorometric chemosensor for selective Hg2+ sensing in a near-perfect aqueous solution and bio-imaging.

We report a new 7-nitrobenzo-2-oxa-1, 3-diazolyl (NBD)-based chemosensor containing a piperazine derivative, NBDP, for detection of mercury ions in almost 100% aqueous medium. The chemosensor shows sensing exclusively toward Hg2+ with a switch-on fluorescence response at 543 nm, which could be attributed to the blocking of PET (photo-induced electron transfer) process upon complexation with mercury ions. The molar ratio of Hg(Ⅱ) to NBDP in the complex is 1:1 based on the Job's plot and HRMS studies. Optimized configurations of NBDP and NBDP-Hg2+ complexes were simulated by means of DFT calculations. The reversible fluorescence response with low detection limit (19.2 nM) in the pH range of 6.0-7.5 renders NBDP a promising candidate for Hg2+ detection in neutral aqueous environments. For the practical application of the chemosensor, test strips were successfully fabricated for rapid detection of Hg2+ ions. Moreover, the utility of NBDP showing the mercury recognition in Human liver cancer cells (SMMC-7721) and zebrafish as well as in live tissues of Arabidopsis thaliana has been demonstrated as monitored by fluorescence imaging.

Benzenebistriazole-strapped calix[4]pyrrole: a neutral anion receptor with CH and NH donor groups that exhibits high sulfate binding affinity and selectivity in aqueous solutions.

A calix[4]pyrrole strapped by benzenebistriazole has been prepared as an artificial anion binding receptor. This neutral anion receptor shows high sulfate binding affinity and selectivity in an aqueous solution. In solid state, the receptor binds the sulfate anion in a chair-like 3D cavity via multiple N-H and C-H hydrogen bonds.

A new colorimetric and ratiometric fluorescent probe for selective recognition of cyanide in aqueous media.

A simple naphthopyran derivative (L) has been synthesized as a colorimetric and ratiometric fluorescent probe for cyanide sensing in the aqueous DMSO medium and paper strips. The nucleophilic addition of CN- to this probe blocks the π-conjugation and the intramolecular charge transfer (ICT) transition between naphthopyran and benzoindolium moieties and consequently results in remarkable color and spectral changes. Upon addition of cyanide, L displayed a ratiometric fluorescence response with a blue shift of the peak position and a noticeable color change from fuchsia to colorless within 90s. The probe exhibits high selectivity and sensitivity toward CN- over other anions and the detection limit was calculated to be 7.56×10-7M, which is well below the WHO cyanide standard in drinking water (1.9µM). In addition, the excitation and emission of the probe were within the visible wavelength range, which could benefit an application of the probe in an inexpensive portable cyanide sensor. The sensing ability of L has been successfully applied in real water samples. Furthermore, test strips based on L were fabricated, which can act as convenient and efficient test kits for detecting CN-.

Palladium-Catalyzed Controllable Reductive/Oxidative Heck Coupling between Cyclic Enones and Thiophenes via C-H Activation.

Herein, we report a straightforward, environmentally friendly, and controllable palladium/ligand catalytic system to enable reductive/oxidative Heck reactions of cyclic enones with thiophene or furan derivatives via C-H activation. The key to this tunable reaction is the appropriate intercepting thienyl-Pd(II)-enolate during the enolization process. Such a controllable and economic protocol would not only provide efficient methods to construct various value-added ß-heteroarylated cyclic ketones/enones but also shed light on developing other conjugate addition reactions via C-H activation.

Study on the supramolecular system of 5-(p-hydroxyphenyl)-10,15,20-tris-(4-chlorophenyl)porphyrin with cyclodextrins and its analytical characteristics.

The supramolecular systems of 5-(p-hydroxyphenyl)-10,15,20-tris-(4-chlorophenyl)porphyrin (p-HTClPP) with beta-cyclodextrin (beta-CD), heptakis(2,3,6-tri-O-methyl)-beta-CD (TM-beta-CD), carboxymethyl-beta-cyclodextrin (CM-beta-CD) and sulfurbutylether-beta-CD (SBE-beta-CD) have been investigated by means of absorption, fluorescence and (1)H NMR spectroscopy. The formation of inclusion complexes has been confirmed on the base of changes of spectroscopy properties. "The double reciprocal method" has been used to determine the stoichiometry and the inclusion constants of p-HTClPP with the four cyclodextrins (CDs). The results show that p-HTClPP can form 1:1 inclusion complexes with the four CDs. Compared with parent native beta-CD, the inclusion abilities of modified beta-CDs with p-HTClPP are stronger. It indicates that the hydrophobic effect plays an important role in the inclusion procedure. The mechanism of inclusion interaction was examined by (1)H NMR technique. During the study of p-HTClPP-TM-beta-CD supramolecular complex, an efficient enhancement of fluorescence intensity was observed. Based on this phenomenon, fluorometric method for the determination of p-HTClPP was developed. The relationship between fluorescence intensity and the concentration of p-HTClPP is linear from 1.0 x 10(-9) to 7.0 x 10(-6)mol L(-1). The limit of detection is 8.3 x 10(-10)mol L(-1) and the relative standard deviation (R.S.D.) is 1.3% (n=8). This research will provide useful information for further application of p-HTClPP.

Palladium-catalyzed dehydrogenative coupling of cyclic enones with thiophenes: a rapid access to ß-heteroarylated cyclic enones.

Dehydrogenative coupling of cyclic enones with heteroarenes has been a longstanding challenge because of the competitive ketone dehydrogenation and conjugated addition. Herein, a dehydrogenative coupling reaction of cyclic enones of different sizes with substituted thiophenes to construct ß-thienyl cyclic enone compounds through palladium-catalyzed C-H functionalization under mild reaction conditions is reported. Simple substituted thiophenes with different functional groups can be directly introduced into cyclic enones with predominant regioselectivity at the α position of thiophene moieties and excellent functional group tolerance. Further molecular transformations of the coupling products to synthetically useful meta-heteroarylated phenol derivatives have also been demonstrated.

Colorimetric and fluorometric dual sensing of trace water in methanol based on a Schiff Base-Al3+ ensemble probe.

A new julolidine based Schiff base receptor (L) was synthesized and characterized. L forms a 1:1 complex with Al3+ in methanol, resulting in an immediate color change from chartreuse to orange and a remarkable enhancement in its emission intensity along with a bathochromic shift from 540 nm to 570 nm. Addition of trace amounts of water significantly quenches the fluorescence emission, where a decomplexation of Al3+ from the L-Al3+ complex takes place. The significant quenching effect indicated that the L-Al3+ ensemble system can be used to detect trace water in commercial methanol. From the fluorescence titration, the detection limit for sensing water in methanol was estimated to be 0.0047%. We have also made an easy-to-prepare test strip of L-Al3+ to detect water in methanol through naked-eye observation, which is possible to realize in situ monitoring.

Diterpenes from buds of Wikstroemia chamaedaphne showing anti-hepatitis B virus activities.

Phytochemical study of the buds of Wikstroemia chamaedaphne Meisn. led to the isolation of seven previously undescribed diterpenes, including one tigliane diterpene (wikstchalide A), two daphnane diterpenes (wikstroelides W-X), and four lathyrane diterpenes (laurifoliosides A-B and 2-epi-laurifoliosides A-B), along with four known diterpenes. The structures of these compounds were established by extensive spectroscopic evidence and electronic circular dichroism (ECD) calculations. Wikstchalide A possesses a 5,6-epoxy ring in the tigliane skeleton. Two compounds exhibited potential anti-hepatitis B virus activities, with IC50 values of 46.5 and 88.3 µg/mL against hepatitis B virus (HBV) surface antigen (HBsAg), and six compounds showed certain inhibitory effects on HBV-DNA replication with the inhibition ratios ranging from 2.0% to 33.0% at the concentrations ranging from 0.39 to 6.25 µg/mL.

Preparation and study on the solid inclusion complex of cloxacillin sodium with beta-cyclodextrin.

The interaction of cloxacillin sodium with beta-cyclodextrin (beta-CD) has been studied by several analytical techniques, including (1)H NMR, fluorescence spectroscopy, infrared spectroscopy. In this paper, solid inclusion complex of cloxacillin sodium with beta-CD was synthesized by the coprecipitation method. In addition, the characterization of the inclusion complex has been proved by fluorimetry, infrared spectroscopy and 1D, 2D NMR. The experimental results confirmed the existence of 1:1 inclusion complex of cloxacillin sodium with beta-CD. The formation constant of complex was determined by fluorescence method and (1)H NMR. Spacial configuration of complex has been proposed on 2D NMR technique.

Study on the interaction of 5-pyridine-10,15,20-tris-(p-chlorophenyl)porphyrin with cyclodextrins and DNA by spectroscopy.

The interaction of 5-pyridine-10,15,20-tris-(p-chlorophenyl)porphyrin (PyTPP) with beta-CD and TM-beta-CD were examined by UV-vis absorption, fluorescence and (1)H NMR spectroscopy. PyTPP prefers to form the 1:1 inclusion complex with TM-beta-CD but hardly form inclusion complex with beta-CD. An inclusion constant (K) for the formation of PyTPP-TM-beta-CD inclusion complex has been evaluated to be 4.4x10(3)L/mol from the absorbance changes. This K value is nearly the same as that 4.5x10(3)L/mol obtained from the fluorescence intensity changes. Compared to beta-CD, the inclusion ability of TM-beta-CD with PyTPP is stronger. It indicates that the hydrophobic effect plays an important role in the inclusion procedure. The mechanism of inclusion interaction was carried out by 1H NMR technique. Furthermore, the interaction of PyTPP with DNA is shown here. It can bind DNA by out-side stacking along the DNA helix but not by intercalation because of the high electron density in the porphyrin core. The binding constant and binding number of PyTPP to DNA are 4.3x10(3) and 1.3, respectively. The interaction of PyTPP with DNA was further carried out in the presence of TM-beta-CD. The significant decrease of the binding constant and binding number were observed and the interaction of porphyrin-bound DNA has been inhibited, which was due to the fact that PyTPP inter into the cavity of TM-beta-CD and influence binding affinity of PyTPP to DNA.

Acid Promoted Direct Cross-Coupling of Methyl Ketones with Dimethyl Sulfoxide: Access to Ketoallyl Methylsulfides and -sulfones.

A new strategy to prepare ß-acyl allylic methylsulfides and -sulfones through acid promoted direct cross-coupling of methyl ketones with dimethyl sulfoxide (DMSO) is reported. The reaction proceeded through the nucleophilic attack of enamine intermidiates derived from ketones to in situ generated thionium ion species, followed by elimination of methanthiol to give ketoallylic methylsulfides. With the prolonged reaction time, such products could be further reacted with a methyl sulfonyl radical, which might be generated from a methylthiosulfonate species, to afford ketoallylic methylsulfones in high yields. Molecular transformations of the allylic methylsulfides were also demonstrated.

A single pH fluorescent probe for biosensing and imaging of extreme acidity and extreme alkalinity.

A simple tailor-made pH fluorescent probe 2-benzothiazole (N-ethylcarbazole-3-yl) hydrazone (Probe) is facilely synthesized by the condensation reaction of 2-hydrazinobenzothiazole with N-ethylcarbazole-3-formaldehyde, which is a useful fluorescent probe for monitoring extremely acidic and alkaline pH, quantitatively. The pH titrations indicate that Probe displays a remarkable emission enhancement with a pKa of 2.73 and responds linearly to minor pH fluctuations within the extremely acidic range of 2.21-3.30. Interestingly, Probe also exhibits strong pH-dependent characteristics with pKa 11.28 and linear response to extreme-alkalinity range of 10.41-12.43. In addition, Probe shows a large Stokes shift of 84 nm under extremely acidic and alkaline conditions, high selectivity, excellent sensitivity, good water-solubility and fine stability, all of which are favorable for intracellular pH imaging. The probe is further successfully applied to image extremely acidic and alkaline pH values fluctuations in E. coli cells.

Preparation and characterization of inclusion complexes of pefloxacin mesylate with three kinds of cyclodextrins.

The ability of alpha-cyclodextrin, beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin (alpha-CD, beta-CD and HP-beta-CD) to break pefloxacin mesylate (PM) aggregates by forming inclusion complexes has been studied using 1H NMR (nuclear magnetic resonance spectroscopy), 13C NMR and fluorescence spectra. The inclusion constants are determined to compare the corresponding inclusion capacity. Solid-inclusion complexes of PM with CDs are synthesized by coprecipitation method, and all the inclusion ratios are found to be 1:1. Additionally, spatial characterization of complexes has been proposed based on two-dimensional nuclear magnetic resonance technique (2D NMR) and spatial conformation is also investigated to propose two possible models between PM and CDs.

Naphthol-based fluorescent sensors for aluminium ion and application to bioimaging.

Three naphthol Schiff base-type fluorescent sensors, 1,3-Bis(2-hydroxy-1-naphthylideneamino)propane (L1), 1,3-Bis(1-naphthylideneamino)-2-hydroxypropane (L2) and 1,3-Bis(2-hydroxy-1-naphthylideneamino)-2-hydroxypropane (L3), have been synthesized. Their recognition abilities for Al(3+) are studied by fluorescence spectra. Coordination with Al(3+) inhibited the CN isomerization of Schiff base which intensely increase the fluorescence of L1-L3. Possessing a suitable space coordination structure, L3 is a best selective probe for Al(3+) over other metal ions in MeOH-HEPES buffer (3/7, V/V, pH=6.6, 25°C, λem=435nm). A turn-on ratio over 140-fold is triggered with the addition of 1.0 equiv. Al(3+) to L3. The binding constant Ka of L3-Al(3+) is found to be 1.01×10(6.5)M(-1) in a 1:1 complex mode. The detection limit for Al(3+) is 0.05µM. Theoretical calculations have also been included in support of the configuration of the L3-Al(3+) complex. Importantly, the probe L3 has been successfully used for fluorescence imaging in colon cancer SW480 cells.