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

A green synthesis of isatoic anhydrides from isatins with urea-hydrogen peroxide complex and ultrasound

The oxidation of isatins at room temperature, using the cheap and environmentally friendly urea-hydrogen peroxide complex and ultrasonic irradiation, has been investigated. The ultrasonic irradiation dramatically reduces the reaction time. With easy and reproducible reaction procedures, different isatoic anhydrides were obtained in excellent yield and with high purity.The authors acknowledge support for this work from the Ministerio de Ciencia y Tecnología through project CTQ2005-01060 and a Grant (SAB2004-0060) for T.D. as a Visiting Professor

Thermodynamic characterization of the dimerization equilibrium of newly synthesized polymethine cyanine dyes

The monomer–dimer equilibrium and thermodynamics of three new cyanine dyes were investigated by spectrophotometric and chemometric methods. The dimerization constants of these new cyanine dyes were determined by studying the dependence of their absorption spectra on the temperature in the range 25–80 °C at concentrations of 3.0×10-4, 1.9×10-4 and 1.1×10-4 M for dye 1, 2 and 3, respectively. The processing of the data, performed for the quantitative analysis of pure spectral profiles, was based on the simultaneous resolution of the overlapping bands in the whole set of absorption spectra. From the dimerization constant and its dependence on temperature, the values of the standard enthalpy change and entropy change of dimerization were calculated

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

Novel Trimethine Cyanine Dye as Potential Amyloid Marker

The applicability of the novel cyanine dye AK 3-1 to the detection and characterization of pathogenic protein aggregates, amyloid fibrils, was tested using the absorption spectroscopy technique. In an organic solvent dimethyl sulfoxide (DMSO), absorption spectra of AK3-1 exhibits vibrational structure with the relative intensity of 0-0 sub-band being higher than that for the 0-1 sub-band. In an aqueous phase the dye absorption band undergoes hypsochromic shift relative to DMSO due to H-aggregation of the dye. The interaction of AK3-1 with the native and fibrillar insulin was followed by the decrease of monomer band and the enhancement of H-dimer band. To evaluate the relative contributions of the monomeric and aggregated forms, the absorption spectra of the protein-bound dye were deconvoluted using the asymmetric log-normal (LN) function. The analysis of the set of fitting parameters provides evidence for the protein-induced AK3-1 self-association into the head-to-head dimers, with the magnitude of this effect being much more pronounced for fibrillar protein form. The molecular docking studies showed that the AK3-1 monomer tends to associate with the specific arrangement of side chains in the β-sheet formed by L17 leucine residues (of the insulin B-chain), located on the dry steric zipper interface of the fibril, while the dye dimers form stable complexes with the amyloid groove formed by the residues Q15 and E17 of the A-chain, and located on the wet interface of the fibril. The latter binding site is more easily accessible and is additionally stabilized by the electrostatic interactions between the positively charged dye and the E17 residue. This binding mode seems to be prevailing over that for the AK3-1 monomers. Based on the results obtained, AK3-1 may be recommended as a prospective amyloid marker complementary to the classical amyloid reporters Thioflavin T and Congo Red

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

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