New Charge Transfer Complexes of K+-Channel-Blocker Drug (Amifampridine; AMFP) for Sensitive Detection; Solution Investigations and DFT Studies

UV–Vis spectroscopy was used to investigate two new charge transfer (CT) complexes formed between the K⁺-channel-blocker amifampridine (AMFP) drug and the two π-acceptors 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) and tetracyanoethylene (TCNE) in different solvents. The molecular composition of the new CT complexes was estimated using the continuous variations method and found to be 1:1 for both complexes. The formed CT complexes’ electronic spectra data were further employed for calculating the formation constants (K_CT), molar extinction coefficients (ε_CT), and physical parameters at various temperatures, and the results demonstrated the high stability of both complexes. In addition, sensitive spectrophotometric methods for quantifying AMFP in its pure form were proposed and statistically validated. Furthermore, DFT calculations were used to predict the molecular structures of AMFP–DDQ and AMFP–TCNE complexes in CHCl₃. TD-DFT calculations were also used to predict the electronic spectra of both complexes. A CT-based transition band (exp. 399 and 417 nm) for the AMFP–TCNE complex was calculated at 411.5 nm (f = 0.105, HOMO-1 → LUMO). The two absorption bands at 459 nm (calc. 426.9 nm, f = 0.054) and 584 nm (calc. 628.1 nm, f = 0.111) of the AMFP–DDQ complex were theoretically assigned to HOMO-1 → LUMO and HOMO → LUMO excitations, respectively.     

A New Pt(II) Complex with Anionic s-Triazine Based NNO-Donor Ligand: Synthesis,X-ray Structure,Hirshfeld Analysis and DFT Studies

The reaction of PtCl₂ with s-triazine-type ligand (HTriaz) (1:1) in acetone under heating afforded a new [Pt(Triaz)Cl] complex. Single-crystal X-ray diffraction analysis showed that the ligand (HTriaz) is an NNO tridentate chelate via two N-atoms from the s-triazine and hydrazone moieties and one oxygen from the deprotonated phenolic OH. The coordination environment of the Pt(II) is completed by one Cl⁻¹ ion trans to the Pt-N_(hydrazone). Hirshfeld surface analysis showed that the most dominant interactions are the H···H, H···C and O···H intermolecular contacts. These interactions contributed by 60.9, 11.2 and 8.3% from the whole fingerprint area, respectively. Other minor contributions from the Cl···H, C···N, N···H and C···C contacts were also detected. Among these interactions, the most significant contacts are the O···H, H···C and H···H interactions. The amounts of the electron transfer from the ligand groups to Pt(II) metal center were predicted using NBO calculations. Additionally, the electronic spectra were assigned based on the TD-DFT calculations.     

Curing Kinetics Modeling of Epoxy Modified by Fully Vulcanized Elastomer Nanoparticles Using Rheometry Method

In this study, the curing kinetics of epoxy nanocomposites containing ultra-fine full-vulcanized acrylonitrile butadiene rubber nanoparticles (UFNBRP) at different concentrations of 0, 0.5, 1 and 1.5 wt.% was investigated. In addition, the effect of curing temperatures was studied based on the rheological method under isothermal conditions. The epoxy resin/UFNBRP nanocomposites were characterized via Fourier transform infrared spectroscopy (FTIR). FTIR analysis exhibited the successful preparation of epoxy resin/UFNBRP, due to the existence of the UFNBRP characteristic peaks in the final product spectrum. The morphological structure of the epoxy resin/UFNBRP nanocomposites was investigated by both field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM) studies. The FESEM and TEM studies showed UFNBRP had a spherical structure and was well dispersed in epoxy resin. The chemorheological analysis showed that due to the interactions between UFNBRP and epoxy resin, by increasing UFNBRP concentration at a constant temperature (65, 70 and 75 °C), the curing rate decreases at the gel point. Furthermore, both the curing kinetics modeling and chemorheological analysis demonstrated that the incorporation of 0.5% UFNBRP in epoxy resin matrix reduces the activation energy. The curing kinetic of epoxy resin/UFNBRP nanocomposite was best fitted with the Sestak–Berggren autocatalytic model.     

Novel 1,3-Thiazole Analogues with Potent Activity against Breast Cancer: A Design,Synthesis, In Vitro,and In Silico Study

Breast cancer is the most common cancer in women, responsible for over half a million deaths in 2020. Almost 75% of FDA-approved drugs are mainly nitrogen- and sulfur-containing heterocyclic compounds, implying the importance of such compounds in drug discovery. Among heterocycles, thiazole-based heterocyclic compounds have demonstrated a broad range of pharmacological activities. In the present study, a novel set of 1,3-thiazole derivatives was designed and synthesized based on the coupling of acetophenone derivatives, and phenacyl bromide was substituted as a key reaction step. The activity of synthesized compounds was screened against the proliferation of two breast cancer cell lines (MCF-7 and MDA-MB-231). Almost all compounds exhibited a considerable antiproliferative activity toward the breast cancer cells as compared to staurosporine, with no significant cytotoxicity toward the epithelial cells. Among the synthesized compounds, compound 4 exhibited the most potent antiproliferative activity, with an IC₅₀ of 5.73 and 12.15 µM toward MCF-7 and MDA-MB-231 cells, respectively, compared to staurosporine (IC₅₀ = 6.77 and 7.03 µM, respectively). Exploring the mechanistic insights responsible for the antiproliferative activity of compound 4 revealed that compound 4 possesses a significant inhibitory activity toward the vascular endothelial growth factor receptor-2 (VEGFR-2) with (IC₅₀ = 0.093 µM) compared to Sorafenib (IC₅₀ = 0.059 µM). Further, compound 4 showed the ability to induce programmed cell death by triggering apoptosis and necrosis in MCF-7 cells and to induce cell cycle arrest on MCF-7 cells at the G1 stage while decreasing the cellular population in the G2/M phase. Finally, detailed in silico molecular docking studies affirmed that this class of compounds possesses a considerable binding affinity toward VEGFR2 proteins. Overall, these results indicate that compound 4 could be a promising lead compound for developing potent anti-breast cancer compounds.     

Novel one-dimensional polymeric Cu(II) complexes via Cu(II)-assisted hydrolysis of the 2,4-bis(3,5-dimethyl-1H-pyrazol-1-yl)-6-methoxy-1,3,5-triazine pincer ligand: Synthesis,structure, and antimicrobial activities

Two unexpected one-dimensional coordination polymers, [Cu(PT)(H₂O)Cl]_n 1 and [Cu₂(BPT)(ClO₄)₃(H₂O)₄]_n·2nH₂O 2 , of symmetrical triazine-based ligands were synthesized by Cu(II)-mediated hydrolysis of the 2,4-bis(3,5-dimethyl-1H-pyrazol-1-yl)-6-methoxy-1,3,5-triazine ( MBPT ) pincer ligand. The reaction of Cu(ClO₄)₂·6H₂O with MBPT proceeded via hydrolysis of the methoxy group to produce the dicompartmental 4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-1,3,5-triazin-2(1H)-one ligand ( HBPT ) that then undergoes in situ complexation with Cu(II) to afford 2 . In case of CuCl₂, the reaction proceeds further with C–N cleavage of one pyrazolyl unit leading to the formation of 6-(3,5-dimethyl-1H-pyrazol-1-yl)-1,3,5-triazine-2,4(1H,3H)-dione ligand ( HPT ) that also undergoes in situ complexation with Cu(II) affording 1 . The role of Cu(II) is to increase the Lewis acid reactivity of the water molecule where similar hydrolytic reactions for MBPT were observed in acidic medium in presence of an aqueous HCl (1:1 v/v) solution. The molecular and supramolecular structures of complexes 1 and 2 were investigated using X-ray diffraction of single crystal, Hirshfeld analysis, and density functional theory calculations. The Cl…H (11.7%) and O…H (24.7%) contacts are the most important in 1 , whereas the molecular packing of 2 is controlled mainly by the O…H (58.7%) hydrogen bonds. Complex 2 showed better activity against Escherichia coli, Bacillus subtilis, and Candida albicans compared with the standard antibiotics amoxicillin, tetracycline, and ampicillin. In general, complexes 1 and 2 showed good antimicrobial activity than these antibiotics and have the advantage to be used as both antibacterial and antifungal agents.     

On-plate deposition of oxidized proteins to facilitate protein footprinting studies by radical probe mass spectrometry

The on-plate deposition of oxidized proteins is described to advance footprinting applications by radical probe mass spectrometry (RP-MS). An electrospray ionization (ESI) needle assembly mounted vertically over a 384-target matrix-assisted laser desorption/ionization (MALDI) plate enabled the limited oxidation of proteins as they were released in the charged droplets ahead of their deposition on the plate. This method combined with on-plate proteolytic digestion protocols expedites the analysis of proteins oxidized by RP-MS, and avoids the need to collect and reconstitute samples prior to analysis by MALDI mass spectrometry. Oxidation of peptides from solutions in water as well as an ammonium bicarbonate solution was investigated to test the optimal conditions required for on-plate oxidation of proteins. These comprised of peptides with a wide range of reactive amino acids including Phe, Tyr, Pro, His, Leu, Met and Lys that were previously shown to oxidize in both electrospray discharge and synchrotron radiolysis based footprinting experiments. The on-plate deposition of lysozyme oxidized at electrospray needle voltages of 6 and 9 kV were carried out to demonstrate conditions suitable for footprinting experiments as well as those that induce the onset of protein damage. Copyright ? 2012 John Wiley & Sons, Ltd.     

Electromembrane extraction of zwitterionic compounds as acid or base: Comparison of extraction behavior at acidic and basic pHs

This study has performed on electromembrane extraction (EME) of some zwitterionic compounds based on their acidic and basic properties. High performance liquid chromatography (HPLC) equipped with UV detection was used for determination of model compounds. Cetirizine (CTZ) and mesalazine (MS) were chosen as model compounds, and each of them was extracted from acidic (as a cation) and basic (as an anion) sample solutions, separately. 1-Octanol and 2-nitrophenyl octylether (NPOE) were used as the common supported liquid membrane (SLM) solvents. EME parameters, such as extraction time, extraction voltage and pH of donor and acceptor solutions were studied in details for cationic and anionic forms of each model compound and obtained results for two ionic forms (cationic and anionic) of each compound were compared together. Results showed that zwitterionic compounds could be extracted in both cationic and anionic forms. Moreover, it was found that the extraction of anionic form of each model compound could be done in low voltages when 1-octanol was used as the SLM solvent. Results showed that charge type was not highly effective on the extraction efficiency of model compounds whereas the position of charge within the molecule was the key parameter. In optimized conditions, enrichment factors (EF) of 27–60 that corresponded to recoveries ranging from 39 to 86% were achieved.     

Adding Value to the Oil Cake as a Waste from Oil Processing Industry: Production of Lipase and Protease by <Emphasis Type="Italic">Candida utilis</Emphasis> in Solid State Fermentation

Olive oil cake is a by-product from the olive oil processing industry and can be used for the lipase and protease production by Candida utilis in solid state fermentation. Different carbon and nitrogen sources were evaluated, and the results showed that the supplementation of the substrate with maltose and starch as carbon sources and yeast extract as a nitrogen source significantly increased the lipase production. The best results were obtained with maltose, whereas rather low lipase and protease activities were found with glucose and oleic acid. Response surface methodology and a five-level–three-factor central composite rotatable design were used to evaluate the effects of the initial moisture content, inoculum size and fermentation time on both lipase and protease activity levels. A lipase activity value of ≈25 U g^-1 and a protease activity value of 110 U g^-1 were obtained under the optimized fermentation conditions. An alkaline treatment of the substrate appeared to be efficient, leading to increases of 39% and 133% in the lipase and protease production, respectively. The results showed that the olive cake could be a good source for enzyme production by solid state fermentation.     

Chemical constituents of Cichorium intybus and their inhibitory effects against urease and alpha-chymotrypsin enzymes

Phytochemical investigation of the aerial parts of Cichorium intybus L. resulted in the isolation and identification of two new natural metabolites, 2,6-di[but-3(E)-en-2-onyl]naphthalene (1), and 3,3',4,4'-tetrahydroxychalcone (2), along with nine known compounds. Their structures were determined by spectroscopic techniques including 1D and 2D NMR. The known compounds were identified as scopoletin (3), 4-hydroxyphenylacetic acid (4), 3-hydroxy-4-methoxybenzoic acid (5), 4,4'-dihydroxychalcone (6), 6,7-dihydroxycoumarine (7), 1-triacontanol (8), lupeol (9), beta-sitosterol (10), and beta-sitosterol-3-O-beta-glucopyranoside (11). Compounds 4-6 and 8 are reported for the first time from C. intybus. Compounds 2 and 3 showed weak inhibitory activities against urease and alpha-chymotrypsin enzymes, respectively.