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

Development of fluorochromic polymer doped materials as platforms for temperature sensing using three dansyl derivatives bearing a sulfur bridge

PM003/2016. Funding Information: G. D. thanks to the European Regional Development Fund within the Operational Programme Science and Education for Smart Growth 2014 - 2020 under the Project Center of Excellence: National center of mechatronics and clean technologies - BG05M2OP001-1.001-0008 for the financial support. Publisher Copyright: © 2023 The Author(s)Three novel bis-dansyl derivatives bearing a sulfur bridge have been synthesized, fully characterized, and their photophysical characterization studied in solution, as well as, in the solid state. All compounds exhibit fluorescence emission with quantum yields up to 60%, which vary significantly depending on the solvent used, and the inherent molecular structure. Moreover, these compounds demonstrate positive solvatofluorochromic behaviour emitting from bluish-green to yellow. Kamlet-Taft studies were performed to better understand the solute–solvent interactions. Due to the intrinsic characteristics of the compounds, efforts were made to understand their potential usefulness for environmental remediation and thus metal ion sensing studies were investigated. Compounds L1 and L2 showed high sensitivity to Cu2+ and Hg2+ ions and were found to modulate their emission extensively, with L2 capable of detecting and quantifying up to 4 µM of Hg2+. Considering the solid-state emission of these compounds, the application towards temperature sensing was put forth. L3 was found to quench its emission in a linear relation with temperature up to 170 °C. Several doped polymer thin films were fabricated, which served as a platform to establish a linear relation with temperature beyond their melting point. Polymethylmetacrylate (PMMA) films emitted up to temperatures of 218 °C, which could be fully restored at room temperature. These results suggest the potential application of these bis-chromophoric compounds as molecular thermometers.publishersversionpublishe

Pollutant metal ions detection and preparation of water-soluble fluorescent polymeric particles

Funding Information: G.D. thanks to the European Regional Development Fund within the Operational Programme Science and Education for Smart Growth 2014–2020 under the Project Center of Exellence: National center of mechatronics and clean technologies - BG05M2OP001-1.001-0008 for the financial support. Funding Information: This work was supported by the Associate Laboratory for Green Chemistry - LAQV which is financed by national funds from FCT/MCTES ( UIDB/50006/2020 and UIDP/50006/2020 ) as well as the PROTEOMASS Scientific Society (Portugal) for funding support (General Funding Grant 2022–2023). F.D. thanks to FCT / MEC (Portugal) for his doctoral grant 2021.05161.BD . E.O thanks FCT / MEC (Portugal) for the individual contract, CEECIND/00648/2017. J.F-.L. thanks the FCT / MEC (Portugal) for the individual research contract DL57. HMS acknowledges the Associate Laboratory for Green Chemistry-LAQV ( LA/P/0008/2020 ) funded by FCT / MCTES for his research contract. Funding Information: The financial support by the Bulgarian National Science Fund (BNSF) under grant – “Novel styryl and polymethine fluorophores as potential theranostic agents “contract N◦ КП-06-М59/1 from 15.11.2021 is gratefully acknowledged by A.K. This work is also developed and acknowledged by A.K. as part of contract №: BG-RRP-2.004-0002-C01, Laboratory of Organic Functional Materials (Project BiOrgaMCT), Procedure BG-RRP-2.004, Establishing of a network of research higher education institutions in Bulgaria”, funded by BULGARIAN NATIONAL RECOVERY AND RESILIENCE PLAN ”. Publisher Copyright: © 2023 The AuthorsPolarity-sensitive dansyl derivatives L1 and L2 were synthesized and their ability to sense pollutant metal ions was investigated. All compounds were found to be highly sensitive towards Cu2+ and Hg2+ metal ions, while L2 being able to detect and quantify Hg2+ concentrations as low as 2.5 μM. Both L1 and L2 exhibit positive solvatofluorochromic behaviour, modulated in the presence of water, which in turn results in fluorescence enhancement via aggregation-induced emission (AIE). Seeking stability and water solubility, luminescent L1-based polystyrene-block-polybutadiene-block-polystyrene (SBS) microparticles (size: 520 ± 76 nm) were successfully prepared while maintaining the fluorescence emission of fluorophore L1 (φ = 22%). This work exemplifies the multiple properties of dansyl-derivatives and their promising applications in biomedicine and environmental fields.publishersversionpublishe

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

CCDC 1879001: Experimental Crystal Structure Determination

Data associated with the article "Pavic, A., Savić, N. D., Glišić, B. Đ., Crochet, A., Vojnovic, S., Kurutos, A., ... & Djuran, M. I. (2019). Silver (I) complexes with 4, 7-phenanthroline efficient in rescuing the zebrafish embryos of lethal Candida albicans infection. Journal of Inorganic Biochemistry."Supplementary material for: [http://dx.doi.org/10.1016/j.jinorgbio.2019.03.017]Related to published version: [https://vinar.vin.bg.ac.rs/handle/123456789/8127

Silver(I) complexes with 4,7-phenanthroline efficient in rescuing the zebrafish embryos of lethal Candida albicans infection

Five novel silver(I) complexes with 4,7-phenanthroline (4,7-phen), [Ag(NO3-O)(4,7- phen-μ-N4,N7)]n (1), [Ag(ClO4-О)(4,7-phen-μ-N4,N7)]n (2), [Ag(CF3COO-O)(4,7- phen-μ-N4,N7)]n (3), [Ag2(H2O)0.58(4,7-phen)3](SbF6)2 (4) and {[Ag2(H2O)(4,7- phen-μ-N4,N7)2](BF4)2}n (5) were synthesized, structurally elucidated and biologically evaluated. These complexes showed selectivity towards Candida spp. in comparison to the tested bacteria and effectively inhibited the growth of four different Candida species, particularly of C. albicans strains, with minimal inhibitory concentrations (MICs) in the range of 2.0–10.0 μM. In order to evaluate the therapeutic potential of 1–5, in vivo toxicity studies were conducted in the zebrafish model. Based on the favorable therapeutic profiles, complexes 1, 3 and 5 were selected for the evaluation of their antifungal efficacy in vivo using the zebrafish model of lethal disseminated candidiasis. Complexes 1 and 3 efficiently controlled and prevented fungal filamentation even at sub-MIC doses, while drastically increased the survival of the infected embryos. Moreover, at the MIC doses, both complexes totally prevented C. albicans filamentation and rescued almost all infected fish of the fatal infection outcome. On the other side, complex 5, which demonstrated the highest antifungal activity in vitro, affected the neutrophils occurrence of the infected host, failed to inhibit the C. albicans cells filamentation and showed a poor potential to cure candidal infection, highlighting the importance of the in vivo activity evaluation early in the therapeutic design and development process. The mechanism of action of the investigated silver(I) complexes was related to the induction of reactive oxygen species (ROS) response in C. albicans, with DNA being one of the possible target biomolecules

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