2,3-Dimethylbenzoxazolium Methosulfate

An economically benign solvent-free approach to synthesise 2, 3-dimethylbenzoxazolium methosulfate is reported in the present work. The title compound is derived from 2-methylbenzoxazole reacting with a slight excess of dimethylsulfate, at room temperature. The reaction proceeds via an intrinsic exothermic reaction, and the benzoxazolium salt crystallized after a short time into a white crystalline form. The product was filtered off and washed with acetone and diethyl ether to provide the desired product in 89% yield. The target compound was evaluated by ESI/MS analysis

Cyanine dyes derived inhibition of insulin fibrillization

The potential of novel cyanine dyes to inhibit the insulin amyloid formation was evaluated using thioflavin T fluorescence assay, quantum-chemical calculations, molecular docking and molecular dynamics simulations. According to the ability to suppress the insulin fibrillization under physiological conditions the examined compounds were found to follow the order: trimethines > pentamethines > monomethines > heptamethines. Of these, the trimethines 3-3 and 3-5, and pentamethines 5-3 and 5-9 almost completely prevented the protein aggregation by retarding both nucleation (except 3-3) and elongation processes. The quantum-chemical calculations revealed a complex relationship between the dye structure and its inhibitory effects. The molecular docking studies showed that most cyanines bind specifically to the L17 ladder of the B chain, located at the dry steric zipper of the insulin fibril protofilament, and form the stable complexes with the helices of the insulin monomer. The molecular dynamics simulations provided evidence for the increase of insulin helicity in the presence of cyanines. Collectively, the presented findings highlight two possible mechanisms by which cyanines can inhibit the insulin fibrillization: i) stabilization of the native protein structure followed by the retardation of the protein nucleation (all dyes); and ii) blocking the lateral extension of beta-sheets via the dye-protein stacking interactions (3-3, 3-5, 5-3, 5-9). Overall, the obtained results may prove of importance for the design of small molecules capable of preventing amyloid fibril formation by insulin and other proteins. (C) 2018 Elsevier B.V. All rights reserved.Peer reviewe

Novel environmentally benign procedures for the synthesis of styryl dyes

A series of styrylpyridinium, styrylquinolinium and styrylbenzothiazolium dyes have been synthesized by novel environmentally benign procedures. The condensation of 4-methylpyridinium methosulphate, 2- or 4-methylquinolinium methosulphate or 2-methylbenzothiazolium methosulphate with aromatic aldehydes was performed under solvent-free conditions or microwave irradiation in the presence of different basic or acidic reagents. The chemical structures of the derived styrylcyanine dyes were confirmed by 1H NMR and UV–vis spectroscopies and elemental analysis

Association of novel monomethine cyanine dyes with bacteriophage MS2:A fluorescence study

Novel monomethine cyanine dyes Cl-YO, F-YO, Cl-YO-Et, Cl-YO-Bu, and YO-Pent were evaluated as agents to detect and characterise a small virus, the MS2 bacteriophage, using the dye and virus intrinsic fluorescence, kinetic and thermal properties, chemical denaturation, and molecular docking and quantum chemistry modelling. The examined compounds demonstrated enhanced fluorescence responses and high affinities (~1 μM−1) for the intact bacteriophage at physiological ionic strength. The linear Scatchard plots revealed the existence of one binding mode for most dyes. Strong evidence that the cyanines bind to the bacteriophage external surface were obtained, although the possibility of the dye penetration through the virus shell and subsequent complexation with the viral RNA was also tested. The main arguments in favour of the former were that i) the fluorescence of the MS2-bound fluorophores decreased under the influence of protein denaturants, urea and guanidine hydrochloride; ii) the fluorescence responses of the dyes to MS2 and bovine serum albumin were similar; and (iii) one order of magnitude higher sensitivity of the dyes to the yeast RNA was found. Simple docking studies suggested that one cyanine molecule is trapped in a cleft formed by three proteins composing the virus shell. Significant role of electrostatic forces in the stabilisation of the dye-MS2 complexes at low ionic strength (10 mM) was demonstrated, while the influence of steric, hydrophobic, and van-der-Waals interactions was expected to increase at physiological ionic strength. The spectral properties of the novel cyanine dyes compared to other fluorophores demonstrated higher sensitivity of the cyanines to MS2, rendering them promising agents for the investigation of the changes in the virus structure under the influence of heat (Cl-YO-Et, Cl-YO-Bu), denaturants (Cl-YO, F-YO), and ionic strength (all the compounds)

1-(3-Iodopropyl)-4-methylquinolin-1-ium Iodide

A solvent-free “one-pot” synthetic approach to 1-(3-iodopropyl)-4-methylquinolin-1-ium iodide is reported in the present work. The title compound is derived from N-alkylation of 4-methylquinoline with 1,3-diiodopropane proceeded at room temperature. The target quinolinium salt is obtained in a highly pure form. It’s structure was evaluated by 1H-NMR, 13C-NMR, and DEPT135 spectra

Structure-Fluorescence Contrast Relationship in Cyanine DNA Intercalators: Toward Rational Dye Design

The fluorescence enhancement mechanisms of a series of DNA stains of the oxazole yellow (YO) family have been investigated in detail using steady-state and ultrafast time-resolved fluorescence spectroscopy. The strong increase in the fluorescence quantum yield of these dyes upon DNA binding is shown to originate from the inhibition of two distinct processes: 1) isomerisation through large-amplitude motion that non-radiatively deactivates the excited state within a few picoseconds and 2) formation of weakly emitting H-dimers. As the H-dimers are not totally non-fluorescent, their formation is less efficient than isomerisation as a fluorescent contrast mechanism. The propensity of the dyes to form H-dimers and thus to reduce their fluorescence contrast upon DNA binding is shown to depend on several of their structural parameters, such as their monomeric (YO) or homodimeric (YOYO) nature, their substitution and their electric charge. Moreover, these parameters also have a substantial influence on the affinity of the dyes for DNA and on the ensuing sensitivity for DNA detection. The results give new insight into the development and optimisation of fluorescent DNA probes with the highest contrast

Ultrafast Excited-State Dynamics of DNA Fluorescent Intercalators: New Insight into the Fluorescence Enhancement Mechanism

The excited-state dynamics of the DNA bisintercalator YOYO-1 and of two derivatives has been investigated using ultrafast fluorescence up-conversion and time-correlated single photon counting. The free dyes in water exist in two forms: nonaggregated dyes and intramolecular H-type aggregates, the latter form being only very weakly fluorescent because of excitonic interaction. The excited-state dynamics of the nonaggregated dyes is dominated by a nonradiative decay with a time constant of the order of 5 ps associated with large amplitude motion around the monomethine bridge of the cyanine chromophores. The strong fluorescence enhancement observed upon binding of the dyes to DNA is due to both the inhibition of this nonradiative deactivation of the nonaggregated dyes and the dissociation of the aggregates and thus to the disruption of the excitonic interaction. However, the interaction between the two chromophoric moieties in DNA is sufficient to enable ultrafast hopping of the excitation energy as revealed by the decay of the fluorescence anisotropy. Finally, these dyes act as solvation probes since a dynamic fluorescence Stokes shift was observed both in bulk water and in DNA. Very similar time scales were found in bulk water and in DNA