Quinoline Moiety Research Articles

Selective detection of fluoride via amplified donor-acceptor interaction of 6H-indolo[2,3-b]quinoline.

In this report, 6H-indolo[2,3-b]quinoline (hereafter 2a) was synthesized and employed as an optical chemosensor for fluoride. The sensitivity of 2a towards fluoride was established from the change in both the absorption and emission signals. The various in-situ1H NMR, UV-Vis, and density functional studies indicate that the 1:2 binding interaction between 2a and fluoride followed by deprotonation to its corresponding di-anion (2a2-), which in turn boosted the donor-acceptor interaction between indole and quinoline moiety in 2a2-via expansion of torsion angle by 10.2° as compared to 2a. Consequently the significant changes in both the absorption and emission signal of 2a allow us to detect and estimate the concentration of fluoride up to 0.2 μM from the mixture of different anions.

Design, synthesis and biological evaluation of quinoline-indole derivatives as anti-tubulin agents targeting the colchicine binding site

A series of novel isocombretastatin A-4 (isoCA-4) analogs were designed and synthesized by replacing 3,4,5-trimethoylphenyl and isovanillin of isoCA-4 with quinoline and indole moieties, respectively. The structure activity relationships (SARs) of these synthesized quinoline-indole derivatives have been intensively investigated. Two compounds 27c and 34b exhibited the most potent activities against five cancer cell lines with IC50 values ranging from 2 to 11 nM, which were comparable to those of Combretastatin A-4 (CA-4, 1). Further mechanism investigations revealed that 34b effectively inhibited the microtubule polymerization by binding to the colchicine site of tubulin. Further cellular mechanism studies elucidated that 34b disrupted cell microtubule networks, arrested the cell cycle at G2/M phase, induced apoptosis and depolarized mitochondria of K562 cells. Moreover, 34b displayed potent anti-vascular activity in both wound healing and tube formation assays. Importantly, 27c and 34b significantly inhibited tumor growth in H22 xenograft models without apparent toxicity, suggesting that 27c and 34b deserve further research as potent antitumor agents for cancer therapy.

Environmentally Benign Neat Mechanochemical Synthesis and Photophysical Studies of Indolylquinolines via Silica gel Catalyzed Metal free A3‐Coupling

AbstractAn efficient neat mechanochemical method for the synthesis of fluorescent indolylquinonlines via A3‐coupling reaction of 1‐phenylsulfonylindole‐3‐carbaldehyde (1), substituted anilines 2(a–j) and substituted phenylacetylene 3(a,b) using SiO2 as an effective catalyst has been developed. The photophysical properties of newly synthesized indolylquinoline derivatives 4(a–l) were established and it depends on the nature of substituent at C6 position of quinoline moiety.

Indenoquinaldine-Based Unsymmetrical Squaraine Dyes for Near-Infrared Absorption: Investigating the Steric and Electronic Effects in Dye-Sensitized Solar Cells.

A series of near-infrared (NIR)-responsive unsymmetrical squaraine dyes (ISQ1-3) incorporating a fused indenoquinaldine-based donor have been designed and synthesized. C12 alkyl chains were incorporated at the sp3 -hybridized carbon center of the indene unit of the indenoquinaldine in an out-of-plane orientation to control dye aggregation on the surface of titanium dioxide, and indole (ISQ1), benzo[e]indole (ISQ2), and quinoline (ISQ3) moieties were included as the donor component bearing the anchoring carboxy group to extend the absorption in the NIR region and to systematically study the effect of the electronic modification on the performance of dye-sensitized solar cells (DSSC). All the dyes exhibit intense absorption (ϵ≥105 m-1 cm-1 ) in the NIR region, and the dye-adsorbed TiO2 films exhibit broad panchromatic absorption. The incident photon-to-current efficiency (IPCE) spectrum of the ISQ3-based DSSC device displays a panchromatic IPCE response up to 880 nm. Additionally, the ISQ3-sensitized device provides the best efficiency of 4.15 % with a short circuit current density (JSC ) of 10.02 mA cm-2 , open-circuit voltage (VOC ) of 0.58 V, and fill factor (ff) of 72 % in the presence of 10 equivalents of 3α,7α-dihydroxy-5β-cholanic acid (CDCA). Electrochemical impedance spectroscopy analysis showed attenuated charge recombination in the ISQ3-sensitized DSSC, which contributes to its higher value of VOC compared with the other dyes.

Synthesis and Electroluminescent Properties of Quinoline-Substituted Anthracene Derivatives for Organic Light-Emitting Diodes.

In this study, two anthracene derivatives with quinoline moieties were synthesized. To investigate their electroluminescent (EL) properties, multilayered OLEDs with the following sequence; indiumtin-oxide (ITO)/N, N'-di(1-naphthyl)-N, N'-diphenyl-(1,1'-biphenyl)-4,4'-diamine (NPB) (20 nm)/Blue emitting materials (30 nm)/bathophenanthroline (Bphen) (30 nm)/lithium quinolate (Liq) (2 nm)/Al (100 nm) were fabricated using these materials as emitters. Two devices exhibited EL in blue to sky-blue regions. Especially, a device using 2,3-diphenyl-6-(10-(naphthalen-7-yl)anthracen-9-yl)quinoline (1) as an emitting material exhibited blue emission with a luminous efficiency, a power efficiency, an external quantum efficiency, and Commission International de L'Eclairage (CIE) coordinates of 1.01 cd/A, 0.43 lm/W, 0.80% at 20 mA/cm2, and (0.17, 0.22) at 6.0 V, respectively.

Hybrid Molecules: Promising Compounds for the Development of New Treatments Against Leishmaniasis and Chagas Disease.

Leishmaniasis and Chagas disease are endemic pathologies in tropical countries. These cause high morbidity and a public health problem. Current chemotherapies are based on conventional drugs with variable efficacy and toxicity related with the length of therapeutic schemes and high doses. When two pharmacological agents are combined into a single molecule, the result is the so-called hybrid molecule. In the search for new treatments against Chagas disease and leishmaniasis, several studies have shown that hybrid molecules display high antiprotozoal activity and this emerging strategy is quite promising in the field of new drug discovery and development. This review focuses on the antiprotozoal activity of different hybrids obtained from the hybridization of pharmacophores, showing that the most of the efforts have been concentrated in the molecular hybridization of quinoline, chalcone and hydrazone moieties.

Efficient Synthesis, Antimicrobial, Antioxidant Assessments and Geometric Optimization Calculations of Azoles‐ Incorporating Quinoline Moiety

A novel series of Schiff bases, hydrazide, and hydrazine derivatives containing quinoline moiety were synthesized via condensation of 3‐substituted quinolines 1a and 1b with different aromatic amines or hydrazines. Furthermore, various heterocyclic ring systems: 1,3,4‐thiadiazole, thiazolidin‐4‐one, 2‐thioxo‐imidazolidin‐4‐one, and thiazole derivatives 10–13 were synthesized by refluxing hydrazinecarbothioamide derivative 9 with different acetic acid derivatives. Theoretical calculation of the title compounds were carried out using density functional theory method. The geometrical optimization of the prepared target compounds was theoretically analyzed. The synthesized compounds were examined for their antimicrobial and antioxidant activities. The obtained results revealed clearly that compounds 8 and 13 displayed promising activity as an antimicrobial activity and compounds 3, 5, 6, 7, and 9 exhibited better radical scavenging ability.

Synthetic approach to novel glycosyltriazole-3-hydroxyquinolone conjugates and their antimicrobial properties

A synthetic approach to novel 2-(1-glycosyl-1,2,3-triazol-4-yl)-3-hydroxyquinolone conjugates has been developed. The methodology involves preparation of a suitable quinoline intermediate and its subsequent conjugation with various acylated glycosyl azides by CuAAC click reaction. A choice of protective group at quinoline moiety appeared to be crucial for subsequent 3-step deprotection sequence that has to kept glycosyl triazole bond intact. Evaluation of antimicrobial properties of the conjugates revealed that their activity was strongly affected by protecting group of the quinoline moiety. Some of the conjugates inhibited exclusively G+ bacterial strains including honeybee larval pathogen Paenibacillus larvae, which were most susceptible to 2-substituted, particularly 2-glycosylated, dibenzylated quinolines.

Thermally stable benzo[f]quinoline based bipolar host materials for green phosphorescent OLEDs

Abstract New bipolar host materials with the different number of benzo[f]quinoline and carbazole groups were synthesized for green phosphorescent organic light-emitting diodes (PHOLEDs). We controlled the number of the electron transporting benzo[f]quinoline moieties and the hole transporting carbazole moieties to adjust charge balance at the emitting layer (EML) with those bipolar host materials. In addition, we found that they give relatively high triplet energy level (T1 > 2.50 eV) which is suitable for green host materials. As a result, the green PHOLEDs employing those materials together with bis(2-phenylpyridine)(acetylacetonato) iridium (III) [Ir(ppy)2(acac)] as a dopant showed moderately high current efficiency up to 42.85 cd/A.

The Influence of the Quinoline Moiety on Direct Pd‐Catalyzed Arylation of Five‐Membered Heterocycles

Herein we report a study on the reactivity of C2‐quinoline‐substituted furan, thiophene and pyrrole derivatives in palladium‐catalyzed direct C–H arylation. The regioselectivity of the reaction was strongly influenced by site position of the attached five‐membered heterocycle thus giving rise to C3‐ and/or C5‐arylated products. Furthermore, the Hammett correlation performed on 5‐substituted‐8‐(furan‐2‐yl)quinolines indicates that a marginally positive charge is building up in the rate determining transition state and thus pointing towards the electrophilic metalation‐deprotonation reaction mechanism.

Synthesis of C-2 and C-3 substituted quinolines and their evaluation as anti-HIV-1 agents

A plenty of natural products and synthetic derivatives containing quinoline moiety have been reported to possess various pharmacological activities. Quinolines such as 2-styrylquinolines and 8-hydroxyquinolines are extensively studied for their anti-HIV-1 activity and found to act mainly through HIV-1 integrase enzyme inhibition. In continuation of our efforts to search for newer anti-HIV-1 molecules, thirty-one quinoline derivatives with different linkers to ancillary phenyl ring were synthesized and evaluated for in vitro anti-HIV-1 activity using TZM-bl assays. Compound 31 showed higher activity in TZM-bl cell line against HIV-1VB59 and HIV-1UG070 cell associated virus (IC50 3.35 ± 0.87 and 2.57 ± 0.71 μM) as compared to other derivatives. Compound 31 was further tested against cell free virus HIV-1VB59 and HIV-1UG070 (IC50 1.27 ± 0.31 and 2.88 ± 1.79 μM, TI 42.20 and 18.61, respectively). This lead molecule also showed good activity in viral entry inhibition assay and cell fusion assay defining its mode of action. The activity of compound 31 was confirmed by testing against HIV-1VB51 in activated peripheral blood mononuclear cells (PBMCs). Binding interactions of 31 were compared with known entry inhibitors.

SERS and DFT study of 5F‐PB‐22

AbstractIn this work, a joint experimental and theoretical study on the synthetic cannabinoid, 5F‐PB‐22 (1‐(5‐fluoropentyl)‐8‐quinolinyl ester‐1H‐indole‐3‐carboxylic acid) is reported. The molecular vibrations of 5F‐PB‐22 were investigated by Raman and surface‐enhanced Raman spectroscopy (SERS) spectroscopies. In parallel, quantum chemical calculations based on density functional theory (DFT) with the hybrid B3LYP exchange‐correlation functional coupled with the standard 3‐21G basis set were used to determine the geometrical and vibrational characteristics of 5F‐PB‐22 and to predict the adsorption geometry of the molecule on the silver colloidal surface. The SERS spectrum of 5F‐PB‐22 was recorded using a 532‐nm laser line and a hydroxylamine phosphate reduced silver colloid as the SERS substrate. SERS and Raman spectral bands have been assigned by comparison with the DFT calculated spectrum. A self‐aggregation spectrum was obtained, but in order to obtain a spectrum with NaCl as the aggregating agent, a two‐step procedure was developed. It was found that 10‐mM NaCl can be used as a trigger for aggregation before adding 5F‐PB‐22 followed by the addition of 20‐ to 100‐mM NaCl to complete aggregation. Using this procedure, 5F‐PB‐22 was easily detected at 2.12 × 10−8 M. Based on a predicted molecular adsorption geometry from the calculated molecular electrostatic potential and the SERS spectrum, it is proposed that the quinoline moiety of the molecule lies in a preponderant parallel orientation to the silver surface with the plane of the indole ring being perpendicular to the surface. The molecular orientation is affected by the surface coverage by 5F‐PB‐22 and the presence of Cl−.

Reactivity of cis‐platinum(II) complexes with 2‐(4‐substituted)phenylthiomethyl)quinoline nonleaving ligands toward thiourea nucleophiles

AbstractThe sequential substitution of aqua ligands from [Pt{2‐(phenylthiomethyl)quinoline}(H2O)2]CF3SO3, Pt(L1), [Pt{2‐(4‐tert‐butylphenylthiomethyl)quinoline}(H2O)2]CF3SO3 Pt(L2), and [Pt{2‐(4‐fluorophenylthiomethyl) quinoline}(H2O)2]CF3SO3 Pt(L3) by thiourea nucleophiles (Nu) was studied under pseudo–first‐order conditions as a function of concentration and temperature using stopped‐flow and UV‐visible spectrophotometric techniques. The observed pseudo–first‐order rate constants for the substitutions can be described by the rate law: kobs(1/2) = k2(1/2)[Nu], where the subscript denotes the consecutive substitution steps. The first aqua ligand was substituted opposite to the strong σ‐trans‐directing thioether followed by the aqua ligand opposite to the quinoline or pyridine moieties. Second‐order rate constants, k2(1st), for the substitution of the first aqua ligand by thiourea nucleophiles ranged between 9 and 22 M−1 s−1 for Pt(L1), 86 and 326 M−1 s−1 for Pt(L2), and 58 –287 M−1 s−1 for Pt(L3). The ranges of the second‐order rate constant, k2(2nd), were always lower than the k2(1st)’s and are 0.3‐9 M−1 s‐1 for Pt(L1), 2‐20 M−1 s−1 for Pt(L2), and 0.3‐5 M−1 s−1 for Pt(L3). Aqua substitution from Pt(L2) is slower for both steps than from Pt4, its pyridyl derivative from our previous study. A Job's method of continuous variation plot suggests a species with a metal‐to‐nucleophile ratio of 1:3 as the ultimate product of the chloride substitution from the Pt(II) complexes by the incoming thiourea nucleophiles. The high and negative activation entropy and low and positive activation enthalpy values support an associative mechanism of activation, characteristic of substitution reactions occurring in square‐planar complexes.

Njaoamine I, a cytotoxic polycyclic alkaloid from the Haplosclerida sponge Haliclona (Reniera) sp.

A new cytotoxic polycyclic alkaloid containing a quinoline moiety, njaoamine I (1) has been isolated from the methanol extract of the sponge Haliclona (Reniera) sp. collected at Okuza Island, Tanzania. The structure of compound 1 was determined by 1D and 2D NMR and HRMS data analysis. Its relative configuration was elucidated by a NOESY experiment and confirmed by comparison of its NMR spectral data to those of njaoamines A–H. Moreover, njaoamine G (2) was also detected by LC/MS analysis of the methanol extract. Njaoamine I (1) displays cytotoxic activity against a panel of three human tumor cell lines in the micromolar range.

Solvent- and Catalyst-Free One-Pot Green Bound-Type Fused Bis-Heterocycles Synthesis via Groebke-Blackburn-Bienaymé Reaction/SNAr/Ring-Chain Azido-Tautomerization Strategy.

A new, efficient, green, endogenous water-triggered, solvent- and catalyst-free ultrasound-assisted one-pot Groebke–Blackburn–Bienaymé reaction/SNAr/ring-chain azido-tautomerization strategy to synthesize bound-type fused bis-heterocycles imidazo or benzo[d]imidazo[2,1-b]thiazoles and 1,5-disubstituted tetrazole (1,5-DsT) containing quinoline moiety is described, which allows synthesis of two types of fused heterocycles in one step under mild green conditions. Antibacterial and antiamebic activities of selected newly synthesized compounds were carried out against three bacterial species: Gram-positive bacterium Staphylococcus aureus ATCC 6538 and Gram-negative bacteria Pseudomonas aeruginosa ATCC 13384 and Escherichia coli O55 and against one amebic species: Entamoeba histolytica.

First Examples of Povarov Reaction of Cyclopentadienones

We describe herein the first examples of Povarov reaction of tetrasubstituted cyclopentadienones in the preparation of quinoline compounds. Polycyclic compounds bearing tetrahydro‐3H‐cyclopenta[c]quinoline and dihydro‐1H‐cyclopenta[c]naphtha[2,3‐h]quinoline moieties have been synthesized by one pot reaction of tetrasubstituted cyclopentadienones with N‐arylamines and formaldehyde in the presence of trifluoroacetic acid. The control of the regioselectivity was total as well with symmetrical and non symmetrical cyclopentadienones. The X‐ray structures of new quinolines were reported.

Different Positron Emission Tomography Tau Tracers Bind to Multiple Binding Sites on the Tau Fibril: Insight from Computational Modeling.

Using the recently reported cryo-EM structure for the tau fibril [ Fitzpatrick et al. (2017) Nature 547, 185-190 ], which is a potential target concerning Alzheimer's disease, we present the first molecular modeling studies on its interaction with various positron emission tomography (PET) tracers. Experimentally, based on the binding assay studies, at least three different high-affinity binding sites have been reported for tracers in the tau fibril. Herein, through integrated modeling using molecular docking, molecular dynamics, and binding free energy calculations, we provide insight into the binding patterns of various tracers to the tau fibril. We suggest that there are four different high-affinity binding sites available for many of the studied tracers showing varying binding affinity to different binding sites. Thus, PBB3 binds most strongly to site 4, and interestingly, this site is not a preferable site for any other tracers. For THK5351, our data show that it strongly binds to sites 3 and 1, the former one being more preferable. We also find that MK6240 and T807 bind to site 1 specifically. The modeling data also give some insight into whether a tracer bound to a specific site can be replaced by others or not. For example, the displacement of T807 by PBB3 as reported experimentally can also be explained and attributed to the larger binding affinity of the latter compound in all binding sites. The binding free energy results explain very well the small binding affinity of THK523 compared to all the aryl quinoline moieties containing THK tracers. The ability of certain tau tracers, like FDDNP and THK523, to bind to amyloid fibrils has also been investigated. Furthermore, such off-target interaction of tau tracers with amyloid beta fibrils has been validated using a quantum mechanical fragmentation approach.

5-Deazaflavinas: síntesis química

Las 5-Deazaflavinas, están involucradas en reacciones enzimáticas redox de una variedad de sistemas biológicos y guardan similitud estructural con la riboflavina. Las propiedades electroquímicas y fotoquímicas son resultado de la sustitución del N-5 del anillo de la isoaloxazina por un átomo de carbono. En esta revisión, se describen los avances en la obtención de 5-deazaflavinas y análogos a partir de ácido barbitúrico, análogos de uracilo, triamino-tricloropirimidinas y quinolincarbonitrilos. El grado y tipo de sustitución de las 5-deazaflavinas, se obtiene a través de los aldehídos y aminas utilizadas, vía reacciones clásicas, simples y convergentes. Comparando las diferentes estrategias sintéticas reportadas, para la construcción de 5-deazaflavinas y análogos, estas se clasifican en dos estrategias generales: i) la construcción del anillo de quinolina sobre el anillo pirimidínico o ii) la construcción del anillo pirimidínico sobre el anillo quinolínico.

Application of spectroelectrochemistry in elucidation of electrochemical mechanism of azoquinoline dye 2-methyl-5-[(E)-phenyldiazenyl]quinolin-8-ol

In situ spectroelectrochemical detection of reaction intermediates was used as a decisive method for elucidation of a rather complex redox mechanism of azoquinoline dye 2-methyl-5-[(E)-phenyldiazenyl]quinolin-8-ol (R-N=N-Ph; where Ph = phenyl, R = 2-methyl-8-hydroxyquinoline fragment). Electrochemical properties were studied in non-aqueous solution by cyclic voltammetry, UV–Vis and IR spectroelectrochemistry and high pressure liquid chromatography with diode array detector. Oxidation and reduction mechanisms involve coupled electron and proton transfers. Oxidation proceeds primarily on hydroxyl group at quinoline moiety and (E)-5-(phenyldiazenyl)quinoline-7,8-diol as the main oxidation product has been suggested. The electrochemically active site for reduction is the azo group. This was proved by in situ UV–Vis and IR spectroelectrochemical data. Detailed analysis of the effects of the presence of acids and bases evidenced the presence of two species in equilibrium: HOR(NH+)-N=N-Ph and HOR-N=N-Ph. The compound containing the hydrazo group (5-(2-phenylhydrazinyl)quinolin-8-ol (R-N=N-Ph) is the main reduction product. Molecular orbital calculations and DFT calculations of IR spectra support the experimental results. In situ IR spectroelectrochemical experiments proved that no reaction of R-N=N-Ph anion or dianion with the solvent acetonitrile was observed during the reduction of the azodye.

Exploration of photophysical properties of green light emitting bis(8-hydroxyquinoline) zinc (Znq2) metal chelate under various environments

Investigations have been made on the photophysical behaviour of 8-hydroxy quinoline zinc metal chelate (Znq2) under various environments such as temperature, humidity, UV radiation, acidic and basic solvents and polymer (PMMA: polymethylmetacrylate) matrix in order to explore the effect of these parameters on the photo luminescence (PL) spectra. Znq2 is solvated in acetic acid and chloroform at different molar concentrations to calculate optical energy band gap as well as to study the shift of π → π* and the n → π* optical transitions in Zn2+ ions and 8-hydroxy quinoline moieties. When the complex was subjected to annealing, the position of the emission peak remained unaltered at 504 nm with hypochromic shift at higher temperatures. The same has been observed when the complex is subjected to humid environment and UV exposure with no alteration in the emission peak in the former case and 1nm alteration in the later. The excitation and emission spectra of Znq2 were recorded in basic and acidic solvents at different molar concentrations so as to establish a relation with the obtained absorption spectra. However, the emission peak blue shifted in basic media and red shifted in acidic media with variation in optical density. The PL spectra of molecular doped Znq2 in PMMA blended films display an emission peak at 499 nm under excitation wavelength of 437 nm. CIE coordinates of Znq2 were found to be close in all considered environments. These results prove that the emission from the synthesized metal complex can be tuned in the wavelength range of 433–524 nm by selecting the solvent or the polymer according to the requirement, inferring its potential as emissive material for the fabrication of organic light emitting diode (OLED), displays as well as in other optoelectronic applications where green light is essential.