Cucurbit[7]uril as the host of adamantane-modified dyes for fluorescence enhancement in aqueous environments.

Taking advantage of the excellent host-guest complexation ability between an auxochrome (adamantane group) and CB[7], the fluorescence emission performance of dyes in water was effectively improved with the addition of two equivalents of CB[7], which provided an efficient method for increasing fluorescence intensity in aqueous environments. Furthermore, these dyes with the host were successfully used in cell imaging.

Why Shot Noise Does Not Generally Detect Pairing in Mesoscopic Superconducting Tunnel Junctions.

The shot noise in tunneling experiments reflects the Poissonian nature of the tunneling process. The shot-noise power is proportional to both the magnitude of the current and the effective charge of the carrier. Shot-noise spectroscopy thus enables us, in principle, to determine the effective charge q of the charge carriers of that tunnel. This can be used to detect electron pairing in superconductors: In the normal state, the noise corresponds to single electron tunneling (q=1e), while in the paired state, the noise corresponds to q=2e. Here, we use a newly developed amplifier to reveal that in typical mesoscopic superconducting junctions, the shot noise does not reflect the signatures of pairing and instead stays at a level corresponding to q=1e. We show that transparency can control the shot noise, and this q=1e is due to the large number of tunneling channels with each having very low transparency. Our results indicate that in typical mesoscopic superconducting junctions, one should expect q=1e noise and lead to design guidelines for junctions that allow the detection of electron pairing.

Improved emission performance of benzo[a]phenoxazine in aqueous solution through host-guest interaction.

To evaluate the contribution of host-guest chemistry in fluorescence enhancement under aqueous conditions, two benzo[a]phenoxazine derivatives with the adamantyl group were prepared. After they formed stable complexes with methyl-ß-cyclodextrin, their emissions at 625-825 nm were greatly increased and fluorescence quantum yields reached 11.5-12.6% in aqueous solution. Furthermore, they were successfully applied in fluorescence labeling of organelles in HeLa cells.

Fluorescence Enhancement of Adamantane-Modified Dyes in Aqueous Solution via Supramolecular Interaction with Methyl-ß-cyclodextrin and Their Application in Cell Imaging.

The fluorescence of functional dyes was generally quenched in aqueous solution, which hindered their application in water-bearing detections. In this work, a novel strategy based on host-guest interaction was provided for the purpose of fluorescence enhancement in aqueous solution and cell imaging. Three adamantane-modified fluorescent dyes (Coum-Ad, NP-Ad, NR-Ad) with coumarin, 1,8-naphthalimide and Nile Red as fluorophores were initially designed and prepared. The ((adamantan-1-yl)methyl)amino group, as the auxochrome of those dyes, complexed with methylated ß-cyclodextrin (M-ß-CD) via supramolecular interaction, and then fluorescent supramolecular nanoparticles (FSNPs) were formed by self-assembly in water. The inclusion equilibrium constant (K) could be as high as 3.94×104  M-1 . With the addition of M-ß-CD, fluorescence quantum yields of these dyes were separately improved to 69.8 %, 32.9 % and 41.3 %. Inspired by the above satisfactory results, six adamantane-modified probes organelle-NPAds with organelle-targeting capability were further obtained. As the formation of hydrogen bonds between organelle-NPAd2 and M-ß-CD verified by theoretical calculation, K of organelle-NPAd2 (5.13×104  M-1 ~4.53×105  M-1 ) with M-ß-CD was higher than that of organelle-NPAd1 (1.15×104  M-1 ~3.66×104  M-1 ) and their fluorescence quantum yields increased to 32.8 %~83.6 % in aqueous solution. In addition, fluorescence enhancement was realized in cell imaging with the addition of M-ß-CD.

Viscosity probes towards different organelles with red emission based on an identical hemicyanine structure.

A series of viscosity probes targeting different organelles were obtained using a single hemicyanine dye as the matrix structure. Specifically, probes 1a-d were obtained by introducing four amines (6-amino-2H-chromen-2-one, N-(2-aminoethyl)-4-methylbenzenesulfonamide, dodecan-1-amine and N,N diphenylbenzene-1,4-diamine) into the indole hemicyanine dye of the carboxylic acid with a D-π-A structure. Their maximum absorption wavelengths were in the range 570-586 nm and they had relatively large molar absorption coefficients, while their maximum emission wavelengths in the red light region were in the range 596-611 nm. Moreover, their fluorescence intensity in glycerol was 35-184 times higher than that in phosphate buffer solution (PBS). The lg(Fl) and lg η of probes 1a-d showed good linearity with high correlation coefficients according to the Förster-Hoffman equation. In addition, cell staining experiments demonstrated that 1a-c could target lysosomes, endoplasmic reticulum and mitochondria, respectively. They could also undergo viscosity-detectable changes in the corresponding organelles under the action of the corresponding ion carriers.

Multiple organelle-targeted 1,8-naphthyridine derivatives for detecting the polarity of organelles.

Four 1,8-naphthyridine derivatives (1a-1d) with different organelle targeting abilities were obtained using the Knoevenagel condensation reaction of 1,8-naphthyridine with 4-(N,N-diethylamino)benzaldehyde (2a), 4-(N,N-diphenylamino)benzaldehyde (2b), 4-(piperazin-1-yl)benzaldehyde (2c) and 4-(ethyl(4-formylphenyl)amino)-N-(2-((4-methylphenyl)sulfonamido)ethyl)butanamide (2d), respectively. The maximal absorption bands of dyes 1a-1d were observed at 375-447 nm, while their maximum emission peaks were situated at 495-605 nm. The optical properties showed that the fluorescence emission of dyes 1a-1d is shifted toward greater wavelengths as the system polarity (Δf) increased. Meanwhile, with increasing polarity of the mixed 1,4-dioxane/H2O system, the fluorescence intensity of dyes 1a-1d gradually decreased. Furthermore, the fluorescence intensity of 1a-1d enhanced by 12-239 fold as the polarity of 1,4-dioxane/H2O mixtures declined. 1a-1d had a large Stokes shift (up to 229 nm) in polar solvents in comparison to nonpolar solvents. The colocalization imaging experiments demonstrated that dyes 1a-1d (3-10 µM) were located in mitochondria, lipid droplets, lysosomes and the endoplasmic reticulum in living HeLa cells, respectively; and they could monitor the polarity fluctuation of the corresponding organelles. Consequently, this work proposes a molecular design idea with different organelle targeting capabilities based on the same new fluorophore, and this molecular design idea may provide more alternatives for polarity-sensitive fluorescent probes with organelle targeting.

Single-electron charge transfer into putative Majorana and trivial modes in individual vortices.

Majorana bound states are putative collective excitations in solids that exhibit the self-conjugate property of Majorana fermions-they are their own antiparticles. In iron-based superconductors, zero-energy states in vortices have been reported as potential Majorana bound states, but the evidence remains controversial. Here, we use scanning tunneling noise spectroscopy to study the tunneling process into vortex bound states in the conventional superconductor NbSe2, and in the putative Majorana platform FeTe0.55Se0.45. We find that tunneling into vortex bound states in both cases exhibits charge transfer of a single electron charge. Our data for the zero-energy bound states in FeTe0.55Se0.45 exclude the possibility of Yu-Shiba-Rusinov states and are consistent with both Majorana bound states and trivial vortex bound states. Our results open an avenue for investigating the exotic states in vortex cores and for future Majorana devices, although further theoretical investigations involving charge dynamics and superconducting tips are necessary.

ESIPT-based fluorescent enhanced probes prompted by methylated ß-cyclodextrin for the detection of thiophenols.

Thiophenol and its derivatives are compounds with high toxicity to organisms and environmental pollution, so it is necessary to detect the level of thiophenols in the environment and biological samples. The probes 1a-b were obtained by introducing the 2,4-dinitrophenyl ether group into diethylcoumarin-salicylaldehyde based compounds. And they can form host-guest compounds with methylated ß-cyclodextrin (M-ß-CD), the association constants of inclusion complexes are 49.2 M-1, 125 M-1 respectively. The fluorescence intensities of probes 1a-b at 600 nm (1a) and 670 nm (1b) increased significantly in thiophenols detection. Meanwhile, with the addition of M-ß-CD, the hydrophobic cavity of M-ß-CD significantly increased the fluorescence intensity of probes 1a-b, thus the detection limits of probes 1a-b to thiophenols were reduced from 410 nM, 365 nM to 62 nM, 33 nM respectively. Whereas, the good selectivity and short response time of probes 1a-b towards thiophenols was not affected in the presence of M-ß-CD. Moreover, probes 1a-b were used for further water sample detection and HeLa cell imaging experiments due to their good response to thiophenols and the results suggested that probes 1a-b had the potential to detect the content of thiophenols in water samples and living cells.

Puddle formation and persistent gaps across the non-mean-field breakdown of superconductivity in overdoped (Pb,Bi)2Sr2CuO6+δ.

The cuprate high-temperature superconductors exhibit many unexplained electronic phases, but the superconductivity at high doping is often believed to be governed by conventional mean-field Bardeen-Cooper-Schrieffer theory1. However, it was shown that the superfluid density vanishes when the transition temperature goes to zero2,3, in contradiction to expectations from Bardeen-Cooper-Schrieffer theory. Our scanning tunnelling spectroscopy measurements in the overdoped regime of the (Pb,Bi)2Sr2CuO6+δ high-temperature superconductor show that this is due to the emergence of nanoscale superconducting puddles in a metallic matrix4,5. Our measurements further reveal that this puddling is driven by gap filling instead of gap closing. The important implication is that it is not a diminishing pairing interaction that causes the breakdown of superconductivity. Unexpectedly, the measured gap-to-filling correlation also reveals that pair breaking by disorder does not play a dominant role and that the mechanism of superconductivity in overdoped cuprate superconductors is qualitatively different from conventional mean-field theory.

Conjugated structures based on quinazolinones and their application in fluorescent labeling.

As an alkaloid, quinazolinone exhibits excellent biological properties; structurally, it also has the potential to construct fluorescent probes with conjugated structures. In this work, probes 5a-c and 6b were obtained by introducing quinazolone into aldehydes with different numbers of double bonds. Their absorption maxima were located at 420-540 nm and their emission maxima were at 500-600 nm in solvents of different polarities. In particular, probe 5c showed significant fluorescence enhancement with the increase in viscosity due to the limited intramolecular rotation, and its fluorescence intensity in glycerol was 37.8 times higher than that in water. Moreover, probes 5a-c and 6b containing the NH structure showed sensitive response to pH, and their fluorescence intensity in alkaline solution (pH 9-11) was suddenly enhanced, which was elucidated with the help of theoretical calculation. In addition, the cell experiments showed that probes 5a and 5b had the ability to target mitochondria and probes 5c and 6b targeted lysosomes in HeLa cells. Furthermore, the viscosity-sensitive probe 5c could be used for monitoring changes in lysosomal viscosity in HeLa cells, which had important guiding significance for designing multi-response fluorogenic probes and promoting the advancement of cancer diagnosis.

Methylated Chromenoquinoline as a Novel Nucleus Fluorescent Probe for Nucleic Acid Imaging.

Two chromenoquinoline-based fluorescent probes 1a-b have been synthesized and investigated. Photofading behaviors of compounds 1a-b showed that at least 89% absorption remained after 6 h irradiating, meanwhile, many of ions and amino acids had negligible impacts on their fluorescence intensity, which meant they had excellent photostability and selectivity. Probes 1a-b exhibited strong absorption and emission in organic solvents with large fluorescence quantum yields, even in water probe 1a still had a relatively large fluorescence quantum yield (20%). Combined with DFT calculation, the influence of alkylation on optical properties of 1b was elucidated. In addition, the fluorescence intensity of probe 1b with red emission enhanced by 5.4-fold and 5.3-fold after DNA and RNA added, and the fluorescence quantum yield increased from 3% to 17% and 14%, respectively, but the neutral molecule 1a had no response to nucleic acid. Furthermore, confocal microscopy imaging of probes 1a-b showed that 1a targeted lipid droplets while the methylated probe 1b to nucleus in living HeLa cells. The results indicated that the subcellular targeting zone could be changed by alkylation of nitrogen atom on chromenoquinoline-based conveniently, which provided a new idea for designing and synthesizing new subcellular labeled probes.

Fluorescent probes based on acridine derivatives and their application in dynamic monitoring of cell polarity variation.

Polarity and viscosity, as important microenvironment parameters, play an essential role in cell metabolism. Therefore, 9-acridine carboxaldehyde reacted with cyano compounds to obtain polarity-sensitive probes 1a-b and viscosity-sensitive probes 1c-d. Among them, with the increase in solvent polarity, the maximum emission wavelength of acridine-dicyanoisophorone-based probe 1a red-shifted from 553 nm to 594 nm, the fluorescence quantum yield increased from 0.5% to 35.6%, and the fluorescence intensity enhanced 38 fold. The acridine-cyanofuranone based probe 1b also has a polarity response similar to 1a. Nevertheless, when the solution viscosity increased from 0.89 cP (100% water) to 856 cP (1% water), the fluorescence intensity of the acridine-tricyanodihydrofuran based probe 1c at 430 nm enhanced 5.6 times. The acridine-cyanobenzothiazole based probe 1d also had a viscosity response similar to 1c. In addition, probes 1a-b were used for further HeLa cell imaging experiments due to their good photostability and the results suggested that probe 1a could locate lipid droplets and probes 1b-c could stain lysosomes. Moreover, probes 1a-b could dynamically monitor the changes in intracellular polarity.

Distinguishing cancer cells from normal cells with an organelle-targeted fluorescent marker.

In this paper we report a hemicyanine dye that is used to distinguish cancer cells from normal cells with its ability to target different organelles. Probe 1, a red emission hemicyanine functional dye, was connected to oxazolo[4,5-b]pyridine and diethylaminobenzene with a double bond. The maximum absorption peaks of probe 1 were located in the 509-552 nm range in organic solvents. Meanwhile, the probe possessed a high molar extinction coefficient (5.50 × 104 M-1 cm-1 in DMSO) with high photostability. The maximum emission wavelength of the probe ranged from 572 nm to 644 nm, and it also had a large Stokes shift (126 nm in DMSO). In particular, the probe showed weak fluorescence in water (Φ = 0.016), whereas it displayed strong fluorescence at 595 nm in ß-cyclodextrin (ß-CD) solution (Φ = 0.13). In addition, cell colocalization experiments showed that probe 1 (3 µM) was located in the endoplasmic reticulum in cancer cells, while it could target lysosomes in normal cells. What's more, further cell imaging experiments demonstrated that the average fluorescence intensity of probe 1 (0.3 µM) in cancer cells increased with the addition of ß-CD, but it did not occur in normal cells. The study provides a convenient way to distinguish cancer cells from normal ones, which has potential for application in the early detection of cancer.

Near-infrared fluorescent probes based on a quinoxaline skeleton for imaging nucleic acids in mitochondria.

In this paper, two cationic probes 1a and 1b and a neutral dye 1c were successfully designed and synthesized according to the Knoevenagel condensation reaction, which combines the good optical properties of hemocyanine and the biocompatibility of nitrogen-containing heterocyclic rings based on a quinoxaline skeleton. Probes 1a and 1b showed an OFF-ON fluorescence response to nucleic acids with excellent selectivity. Specifically, the fluorescence intensity of probe 1a was enhanced by 18 and 133 times, respectively, along with the increase of DNA or RNA concentrations (0-600 µg mL-1). Furthermore, a good linear correlation between the fluorescence intensity of probes 1a and 1b and the concentrations of DNA or RNA (0-350 µg mL-1) was obtained. In particular, the maximum emission wavelengths of probes 1a and 1b reached the near-infrared region (660-664 nm) when DNA or RNA was detected, which might reduce the light damage to cells and facilitate cell experiments. Fluorescence imaging revealed that all three dyes could be localized in the mitochondria of HeLa cells. The difference was that probes 1a and 1b could stain the nucleic acid in the mitochondria, while dye 1c was only a neutral mitochondrial biomarker. The results indicated that probes 1a and 1b are promising in the development of low toxicity mitochondrial nucleic acid probes and are expected to be used in monitoring the normal state of mitochondrial nucleic acids for living cells, which will help improve the situation in that currently reported studies of fluorescent probes are mainly focused on the nucleic acids in the nucleus, but less so on DNA in the mitochondria.

Preparation of Chromeno[b]quinoline Derivatives and Their Application for Lipid Droplets Markers.

Functional dyes with a chromeno[b]quinoline skeleton (3a-d) were synthesized by one-step cyclization between coumarin derivatives and aromatic amines under the promotion of anhydrous aluminum chloride in 41.2-45.8% yields. Their maximum absorption and emission wavelengths locate at 358-396 and 420-603 nm with large Stokes shifts (168-231 nm), and their intramolecular charge transfer has been corroborated by density functional theory calculations. Cell experiments have proved that the probes 3a-c possess the ability to target lipid droplets.

Thiocarbonyl photosensitizer, a feasible way to eliminate the photosensitizer residues in photodynamic therapy.

Photodynamic therapy (PDT) has been successfully applied in clinical treatment several years. However, after finished treatment process the residual photosensitizer will spread throughout body, which forces patients stay in the dark room to avoid exposure in sunlight several weeks. Therefore, develop degradable photosensitizer could effectively eliminate this inconvenience. In the past, researchers have developed degradable photosensitizers based on supramolecular structure. In this study, we achieved the same effect in small molecule level. Three thiocarbonyl photosensitizers (PS) have high photogenerated 1O2 quantum yield and can be photodegraded by laser irradiation within 15 min. And due to its high phototoxicity and low toxicity, thiocarbonyl PS still maintains its high phototoxicity. Especially, mitochondrial targeting PS 1a has better properties than many BODIPY or cyanine heavy-atom-free photosensitizers. It only needs 1 µM to reduce HeLa cell activity to 30%. Finally the thiocarbonyl PS provided a convenient way to solve the PS residue problem without sacrificing PDT efficiency.

Construction of a ratiometric phosgene probe by chromophore formation from auxochrome.

A new fluorescent probe for ratiometric detection of phosgene is reported. This probe was constructed with classic 1,8-naphthalimide and 2-(2-aminophenyl)benzimidazole by Ullmann coupling reaction. After exposure to phosgene, yellow fluorescence weakened while blue fluorescence enhanced significantly. There was a ratiometric response between 542 nm and 490 nm. The detection limit (LOD) was 6.7 nM and the response time was within 200 s in CHCl3. Meaningfully, a new chromophore, benzo [4,5]imidazo[1,2-c]quinazolin-6(5H)-one, was formed after 2-(2-aminophenyl)benzimidazole unit reacted with phosgene, and the ratiometric response was achieved by two chromophores in which the mechanism was confirmed by 1H NMR spectra, HRMS and theoretical calculation. Furthermore, test papers and nanofibers were fabricated with the probe, which could sensitive detection of phosgene within 10 min and 1 min respectively.

Direct evidence for Cooper pairing without a spectral gap in a disordered superconductor above Tc.

The idea that preformed Cooper pairs could exist in a superconductor at temperatures higher than its zero-resistance critical temperature (Tc) has been explored for unconventional, interfacial, and disordered superconductors, but direct experimental evidence is lacking. We used scanning tunneling noise spectroscopy to show that preformed Cooper pairs exist up to temperatures much higher than Tc in the disordered superconductor titanium nitride by observing an enhancement in the shot noise that is equivalent to a change of the effective charge from one to two electron charges. We further show that the spectroscopic gap fills up rather than closes with increasing temperature. Our results demonstrate the existence of a state above Tc that, much like an ordinary metal, has no (pseudo)gap but carries charge through paired electrons.

Design and synthesis of a series of OFF-ON near infrared fluorescent probes for nucleic acid in aqueous solution.

Five cyanine dyes (6a-e) with aza units were prepared by the reaction of pyridinum or quinolinium with suitable aldehydes. They present several remarkable features including large Stokes shift (235-282 nm), long emission wavelength (640-698 nm) and excellent selectivity. Moreover, probes 6a-b display obvious and sensitive fluorescent response to DNA and RNA in aqueous solution, and the quantum yield of probe 6a response to RNA increases from 0 to 8.9%. More importantly, probes 6c and 6e can effectively avoid DNA interference and only respond to RNA in aqueous solution. In addition, laser confocal cell experiment has showed that probe 6b can image the nucleolus of nucleic acids in HeLa cells.

Viscosity sensitive endoplasmic reticulum fluorescent probes based on oxazolopyridinium.

A series of viscosity sensitive fluorescent probes 1a-e were synthesized by linking coumarin and oxazolopyridinium via dimethylene in this paper. The viscosity test of probes 1a-e indicated that the fluorescence intensity of the probes enhanced significantly with the increase of viscosity of the system (0.89-865 cP), and exhibited a nearly OFF-ON response to viscosity at 648 nm, 650 nm and 650 nm, respectively. In addition, cells still had a high survival rate after co-culturing with probes 1a-e for 12 h (94-98%). Meanwhile, the laser confocal experiment showed that the variation of the carbon chain length in the oxazolopyridinium could affect the subcellular region of the localization of the probes in cells. When the length of the carbon chain in oxazolopyridinium was between n-C7H15 and n-C12H23, probes 1b-d had the ability to target the endoplasmic reticulum in the cells. Moreover, probes 1b-d showed no significant change in fluorescence intensity after 35 min of continuous laser confocal irradiation, indicating that they had excellent anti-photobleaching properties.