Indolium Salts Research Articles

Dual-functional fluorescent probe for imaging ROS and hypoxia dynamic in cancer cells

Hypoxia is able to induce the overexpression of nitroreductase (NTR) in cancer cells. Moreover, there is still the controversy about reactive oxygen species (ROS) change under the hypoxic condition. Herein, we designed and synthesized a fluorescent probe WNO that could simultaneously visualize the fluctuation changes of NTR and ROS in hypoxic HeLa cells. WNO consists of 4-nitro-1,8-naphthalimide group and 2,3,3-trimethyl indolium salt. In buffer 4-nitro-1,8-naphthalimide group could selectively response to NTR in the presence of nicotinamide adenine dinucleotide phosphate (NADH), resulting in a strong green fluorescence. However, upon LED light irradiation 2,3,3-trimethyl indolium salt moiety could efficiently convert into Cy3 emitting a red fluorescence. Furthermore, the monitoring for NTR and photoconversion of WNO in hypoxic HeLa cells were investigated in detail by confocal fluorescence imaging through green and red channels, respectively. It was found that WNO could image the intracellular NTR or hypoxia level. Meanwhile, the WNO photoconversion was accelerated largely in hypoxic cells, which resulted from the production of excessive ROS. WNO and/or its photoconversion product mainly accumulated into the mitochondria. Moreover, MTT assay indicated that LED irradiation or hypoxia treatment made the cytotoxicity of WNO increase by 50 %. Additionally, based on ROS-stimulated the photoconversion of WNO, the intracellular ROS and NTR changes in mitochondrial dysfunction and oxidative stress were also investigated. It indicated that WNO was capable of sensitive and rapid imaging the intracellular ROS and NTR levels under both conditions. These findings would provide an excellent foundation for cancer diagnosis and therapy.

Combination of quinoxaline with pentamethinium system: Mitochondrial staining and targeting

Pentamethinium indolium salts are promising fluorescence probes and anticancer agents with high mitochondrial selectivity. We synthesized two indolium pentamethinium salts: a cyclic form with quinoxaline directly incorporated in the pentamethinium chain (cPMS) and an open form with quinoxaline substitution in the γ-position (oPMS). To better understand their properties, we studied their interaction with mitochondrial phospholipids (cardiolipin and phosphatidylcholine) by spectroscopic methods (UV–Vis, fluorescence, and NMR spectroscopy). Both compounds displayed significant affinity for cardiolipin and phosphatidylcholine, which was associated with a strong change in their UV–Vis spectra. Nevertheless, we surprisingly observed that fluorescence properties of cPMS changed in complex with both cardiolipin and phosphatidylcholine, whereas those of oPMS only changed in complex with cardiolipin. Both salts, especially cPMS, display high usability in mitochondrial imaging and are cytotoxic for cancer cells. The above clearly indicates that conjugates of pentamethinium and quinoxaline group, especially cPMS, represent promising structural motifs for designing mitochondrial-specific agents.

Synthesis, photophysical, electrochemical and computational investigation of dimethine and trimethine cyanine-based dyes

Three novel cyanine-based dyes (D1-D3) were obtained by the carboxylic indolium salt the condensation reaction with three different donors, N,N-dimethylaniline, carbazole and indole derivatives. The chemical structures of these dyes were confirmed and fully characterized by IR, NMR, and HRMS. The UV–vis, fluorescence spectra, and cyclic voltammetry were conducted to give a preliminary insight into their optoelectronic properties. Generally, all synthesized dyes exhibited well-defined absorption in the visible region with high absorptivity and low band gap, giving λEx. max (516–564 nm), ε (45279–141011 M−1cm−1) and E0-0 (2.11–2.21 eV). Distinctive stokes shifts were observed for all dyes, with the highest value for the dimethine cyanine containing carbazole donor, D2, (2752 cm−1). The solvatochromic study showed hypsochromic effects and increased Stokes shifts with increasing solvent polarity. The electrochemical study on the other hand revealed having HOMO and LUMO energy levels, <-5.46, and > -3.58 eV, respectively, indicating their suitability as sensitizers in dye sensitized solar cells. The impact of different donors on the geometrical, photophysical, charge transfer and reorganization energy on the designed dyes has been investigated using Density Functional Theory (DFT) and time-dependent (TD-DFT). The theoretical and experimental results are in good agreement. The results indicate that the D1-D3 dyes have a small energy gap (2.50–2.77 eV) and their cationic counterpart absorption in the visible (480–576 nm). The modification of the donor suggests that these dyes would be suitable for dye-sensitized solar cells (DSCCs).

Construction of Tricyclic Nitrogen Heterocycles by a Gold(I)‐Catalyzed Cascade Cyclization of Allenynes and Application to Polycyclic π‐Electron Systems

AbstractA novel approach to the direct construction of tricyclic nitrogen heterocycles based on gold‐catalyzed cascade cyclization of aminoallenynes is described. The expected biscyclization reaction of hydroxyisobutyryl‐protected aminoallenynes was efficiently promoted by a catalytic amount of BrettPhosAuNTf2 in the presence of iPrOH to produce 1,2‐dihydrobenzo[cd]indole derivatives in good yields. When the reaction was combined with Friedel–Crafts acylation or palladium‐catalyzed N‐arylation, the resulting tricyclic products were efficiently converted into nitrogen‐containing polycyclic aromatic compounds (N‐PACs) with highly conjugated π‐electron systems. A newly obtained hexacyclic indolium salt showed characteristic concentration‐dependent absorption and emission properties.

Construction of Tricyclic Nitrogen Heterocycles by a Gold(I)-Catalyzed Cascade Cyclization of Allenynes and Application to Polycyclic π-Electron Systems.

A novel approach to the direct construction of tricyclic nitrogen heterocycles based on gold-catalyzed cascade cyclization of aminoallenynes is described. The expected biscyclization reaction of hydroxyisobutyryl-protected aminoallenynes was efficiently promoted by a catalytic amount of BrettPhosAuNTf2 in the presence of iPrOH to produce 1,2-dihydrobenzo[cd]indole derivatives in good yields. When the reaction was combined with Friedel-Crafts acylation or palladium-catalyzed N-arylation, the resulting tricyclic products were efficiently converted into nitrogen-containing polycyclic aromatic compounds (N-PACs) with highly conjugated π-electron systems. A newly obtained hexacyclic indolium salt showed characteristic concentration-dependent absorption and emission properties.

A Colorimetric and Fluorescent Probe Based on Quinoline‐Indolium for Detection of CN− in Aqueous Media

AbstractA new colorimetric and fluorescent probe (QI) based on quinoline‐indolium was developed for detection of CN−. In an aqueous solution, QI showed high selectivity and strong anti‐interruption for CN−. In addition, it was clearly visible to the naked eyes that the color and fluorescence changes induced by CN− exhibited sharp contrast. The research also found that QI could determine CN− in the range of pH 5–10. The spectral signal was linearly proportional to CN− concentration, and the detection limit was calculated to be low as 41.6 nM. The sensing mechanism of QI to CN− was accomplished via the attachment of CN− at the C atom of indolium salt C=N+ group through the nucleophilic addition, which was confirmed by 1H NMR studies. Notably, we could apply the designed probe for the cycle detection of CN− in a wide pH range, for practical purposes for a long duration. Furthermore, the TLC plates of QI were verified to detect CN− in a simple, rapid way in environmental systems.

A novel indolium salt as a rapid colorimetric probe for cyanide detection in aqueous solution

In this study, a new chemosensor IDTTH for rapid detection of cyanide (CN─) based on 6,6,12,12-Tetrakis(4-hexylphenyl)-6,12-dihydrodithieno[2,3-d:2′,3′-d′]-s-indaceno[1,2-b:5,6-b′]di- thiophene-2,8-dicarboxaldehyde-hemicyanine conjugate has been developed. The 6,6,12,12-tetrakis(4-hexylphenyl)-6,12-dihydrodithi-eno[2,3-d:2′,3′-d′]-s-indaceno[1,2-b:5,6-b′]dithiophene was served as a signal unit and hemicyanine as a recognition unit. This probe shows high selectivity towards CN─ ions among tested anions. Addition of CN─ ions to probe IDTTH in semi-aqueous solution (acetonitrile/H2O = 1/1, V/V) could lead to a 195 nm blue shift of absorption band, together with colour changes from blue to yellow. The sensing mechanism is attributed to the nucleophilic addition between CN─ and the C=N bond of indolium group, which could be clearly clarified through the 1H NMR titration and MS spectral. Moreover, probe IDTTH could be used as the test strips with low cost to detect CN─ ions conveniently by naked eyes.

Synthesis of symetrical near-infrared dyes containing benzo[c,d]indole system

Five symmetrical near infrared dyes having different linker between the two heterocycles were synthesized by condensation of N-alkylbenzo[c,d]indolium salts with either squaric acid or imine. All synthesized dyes showed strong absorbance in the near-infrared region of 850-1015 nm and can be used as nucleic acid detection or fluorescent labeling agents for proteins. Three of the dyes 21, 22 and 25 containing functionalized N-substituents (ester group) can be further modified or covalently attached to target. The structures of these cyanine dyes where characterized by virtue of NMR, UV, MALDI and Elemental analysis.Keywords: Synthesis, cyanine, Polymethine dyes, Near-IR dyes, Absorption, Chromophore.

A novel colorimetric and fluorescent probe based on indolium salt for detection of cyanide in 100% aqueous solution

We reported a novel indolium salt -based colorimetric and fluorescent probe N1 for cyanide. The probe N1 showed a bleaching solution and fluorescence quenching toward CN− in 100% aqueous solution over other anions. In UV-vis and fluorescent spectrometry method, a large blue shift (261 nm), color bleaching and fluorescence quenching was observed. The minimum detection limit on fluorescence response of the probe N1 towards CN− was 3.34 × 10−7 mol/L. This probe N1 operates via intramolecular charge transfer (ICT) mechanism, because the nucleophilic attacking of CN− to the indol CN, the ICT progress was blocked with color changed and fluorescence quenched, which is further confirmed by 1H NMR, MS and DFT studies. Therefore, the synthesized probe would be a promising device for the detection of cyanide.

Large-sized benzo[e]indolium salt single crystals with high optical nonlinearity

Two new benzo[e]indolium salts with highly efficient nonlinear optical performance and excellent crystal characteristics were synthesized.

Near-infrared chemodosimetric probes based on heptamethine cyanine dyes for the “naked-eye” detection of cyanide in aqueous media

Two simple chemodosimetric probes (P1 and P2) based on heptamethine cyanine dyes have been synthesized for highly sensitive and selective detection of cyanide anions (CN−) in aqueous media. The probes with an immobilized indolium salt as the specifically nucleophilic addition reaction site for CN− exhibit absorption bands in the near-infrared (NIR) region (650–850nm). Upon the addition of CN−, the probes display a blue-shifted spectrum and result in apparent color change from green to brilliant yellow that can be easily observed by the naked eye even in the presence of other interfering anions such as F−, AcO−, Br−, NO2−, Cl−, SO42− and I−. There are good linear relationships between the fluorescence intensity of the probes and CN− concentrations, and the detection limits for P1 and P2 are estimated to be 0.017μM and 0.2μM, respectively. The sensing mechanism of the nucleophilic addition is confirmed by 1H NMR and mass spectroscopic analysis. In addition, the probe P2 is employed for cell imaging and the detection of CN− in living cells L929 is successfully realized.

A novel indolium salt as a highly sensitive and selective fluorescent sensor for cyanide detection in water

A highly sensitive fluorescent turn-on cyanide probe is developed based on benzylidenes containing methylindolium group. Three benzylidene derivatives were synthesized from the condensations of three benzaldehyde derivatives and methyleneindoline. Only one of these three derivatives shows strong blue fluorescent response selectively to CN− which can be clearly observed in submicromolar range as the result of the cyanide addition to the indolium group. The detection of cyanide with this compound is optimized in aqueous media using non-ionic surfactant and sonication method to give very low limit of detection in subnanomolar range. The probe is also developed into a paper-based and gel-based sensing kits that can readily detect cyanide ion in micromolar range by naked eye under a common black light (360nm) illumination.

Synthesis, linear and nonlinear optical properties of a new dimethine cyanine dye derived from phenothiazine

Dimethine cyanine dye (PTZIS) based on phenothiazine as the core donor and indolium salt as the acceptor has been synthesized and fully characterized. UV-Vis absorption and fluorescence properties of PTZIS were studied in different solvents. Absorption spectra revealed a large bathochromic shift of the intramolecular charge transfer (ICT) absorption band of PTZIS compared with those in the non-halogenated solvents. Also, the optical data of PTZIS showed a large Stokes shift compared with those in the non-halogenated solvents, indicating a great influence on the geometry of the emissive excited state. The nonlinear optical properties of PTZIS in ethanol solution at different concentrations and different laser powers have been studied using the Z-scan technique with a continuous wave (cw) argon ion laser at 514.5 nm. The closed aperture Z-scan data was used to estimate the nonlinear refractive index n2, while the open aperture scan provided the nonlinear absorption coefficient β. The values obtained are relatively very high and vary linearly with concentration.

ChemInform Abstract: A Novel and One‐Pot Method for Synthesis of Unprecedented 3,3‐Dimethyl‐2‐amide Indoles under Metal‐Free Conditions.

AbstractTitle compounds (III) are prepared via a novel oxidative amination reaction between indolium salts (I) and cyclic secondary amines (II).

Cyanine Dyes

Cyanine dyes are highly conjugated, fluorescent molecules with absorption and emission wavelengths in the near infra-red region (700–900 nm). The simplest synthetic route to heptamethine cyanine dyes 1 (so-called because of the seven carbons in the conjugated backbone) was first described by Narayanan and Patonay who heated N-alkylated indolium salts 2 with 2-chloro-1-formyl-3-(hydroxyl methylene) (3) in a Vilsmeier-type reaction.[1] These heptamethine cyanine scaffolds can be readily modified through displacement of the labile chloride group by nucleophiles,[2] [3] [4] resulting in fluorescent molecules with varying quantum yields, extinction coefficients, and fluorescence maxima. Conjugation to biomolecules is achieved through chlorine substitution by 3-(4-hydroxyphenyl) propionic acid.

Synthesis and near-infrared absorption properties of linearly π-extended squarylium oligomers

Linear squarylium oligomers bearing extended π-conjugation systems were newly synthesized, and their near-infrared (NIR) light-absorbing properties were investigated. Replacement of the iodo substituent in a 5-iodinated indolino-squarylium dye to the 2-hydroxy-3,4-dioxocyclobut-1-en-1-yl functional group via the Pd-catalyzed cross-coupling with a tributylstannylsquarate followed by condensation with a quaternary indolium salt afforded the semi-squarylium-attached squarylium derivative, i.e., the squarylium dimer. The introduction of the semi-squarylium unit gave rise to a significant bathochromic shift towards the NIR region ( λ abs = 763 nm in CHCl 3 at 298 K). Starting from a 5,5′-diiodinated indolino-squarylium, the iterative extension of semi-squarylium units successfully yielded the linearly π-extended trimer and pentamer, that showed absorption maxima at 862 and 940 nm in CHCl 3 at 298 K, respectively. Especially, the pentamer exhibited a considerably low optical band gap of 1.1 eV.

Carbocyanines — derivatives of nitrogen-containing heterocycles with bridging groups in the chromophore

Tetramethylene-2,2′-bis(1,3,3-trimethyl-(3H)-indolium),-3-ethylbenzothiazolium,-1-methyl-quinolinium, and-1-methyl-and-1-butylbenz[c,d]indolium salts were synthesized starting from them trimethinecyanines containing an ethylene bridging group in the α, α′-positions of the chromophore have been prepared. These compounds are converted to their analogs containing a vinylene group by the action of benzoquinones. In the case of thiacarbocyanines the effect of the indicated bridging groups on the conformation and protonation route of the carbocyanines has been studied. The chromaticity of the dyes has been investigated.

3H‐indolium salts efficiently prepared from N‐substituted anilines and α‐branched ketones by an one‐pot synthesis

AbstractStarting with the N‐substituted anilines 4/12 and the α‐branched ketones 3 the 3H‐indolium salts 1 and their fused derivatives 13 are prepared by combining a sodium nitrite nitrosation, a zinc dust reduction, a hydrazone formation and a Fischer indolization to a reaction sequence in which the isolation and purification of intermediates is not necessary. The scope and limitations of this effective one‐pot synthesis are discussed.

Ring Transformations of Heterocyclic Compounds. Part 22. Pyrido[1,2‐a]indolium Salts from 2‐Methyl‐3H‐indoles by Pyrylium Mediated Three Carbon Anellation.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Ring transformations of heterocyclic compounds. XXII. Pyrido[1,2‐a]indolium salts from 2‐methyl‐3H‐indoles by pyrylium mediated three carbon annelation

AbstractThe synthesis of pyrido[1,2‐a]indolium perchlorates 8,11 from 2,4,6‐triarylpyrylium perchlorates 1 and 2‐methyl‐3H‐indoles 6,9 in the presence of a basic condensing agent (anhydrous sodium acetate, piperidine acetate, triethylamine/acetic acid, triethylamine) in ethanol by a 2,4‐[C3+C2N] pyrylium ring transformation is reported. Spectroscopic data of the transformation products and their mode of formation are discussed.