European Journal of Chemistry

A simple and efficient synthesis of substituted pyrazolo[1,5-a]pyrimidine derivatives has been developed by the use of ultrasound. 5-Methyl-4-phenyl-1H-pyrazol-3-amine required for the synthesis of pyrazolo[1,5-a]pyrimidine derivatives has been easily obtained by the reaction of 3-(dimethylamino)-2-phenylacrylonitrile (formed from readily available 2-phenylacetonitrile) with hydrazine hydrate in refluxing ethanol. The 5-aminopyrazole was then reacted with various formylated active proton compounds in presence of KHSO₄ in aqueous medium under ultrasound irradiation to give the desired products. The chemical structures of the newly synthesized compounds were confirmed by IR, ¹H NMR, ¹³C NMR and Mass spectral data. X-ray crystallographic study of a selected compound 6-(4-chlorophenyl)-2-methyl-3-phenylpyrazolo[1,5-a]pyrimidin-7-amine (7c) was performed to ascertain the regioselectivity of the reaction. Crystal data for compound 7c: Triclinic, space group P-1 (no. 2), a = 8.0198(3) Å, b = 14.0341(6) Å, c = 14.2099(6) Å, α = 87.672(2)°, β = 83.902(2)°, γ = 89.120(2)°, V = 1588.87(11) Å³, Z = 4, T = 293(2) K, μ(MoKα) = 0.248 mm^-1, D_calc = 1.400 g/cm³, 12918 reflections measured (4.012° ≤ 2Θ ≤ 49°), 5152 unique (R_int = 0.0411, R_sigma = 0.0429) which were used in all calculations. The final R₁ was 0.0486 (I > 2σ(I)) and wR₂ was 0.1320 (all data).

A quantitative structure activity relationship (QSAR) model for a series of N-(1-benzyl-3,5-dimethyl-1H-pyrazole-4-yl) benzamide derivatives having autophagy inhibitory activities as potent anticancer agents was developed by the multiple linear regressions (MLR) method. In this study, previous compounds were used in the model development were divided into a set of fifteen compounds as training set and set of four compounds as test set. A model with high prediction ability and high correlation coefficients was obtained. This model showed r = 0.968, r² = 0.937 and Q² = 0.880, the QSAR model was also employed to predict the experimental compounds in an external test set, and to predict the activity of a new designed set of 3,5-dimethyl-4-substituted-pyrazole derivatives (1-15), result showed that compound 3 has the most promising inhibition activity (EC₅₀ = 0.869 μM) against human pancreatic ductal adenocarcinoma cell MIA PaCa-2 compared to the reference chloroquine with (EC₅₀ = 14 μM). Thus, the model showed good correlative and predictive ability. Docking studies was performed for designed compounds, docking analysis showed the best compound 1 with high docking affinity of -24.8616 kcal/mol.

This is a quality control study and analysis of Portland cement taken from four Pakistani cement plants (Deewan, Kohat, Lucky and Maple Leaf). These four samples were analysed and the determination of major oxides present was carried out. Loss on ignition and the percentage of insoluble residue was also determined. Our research shows percentage of major oxides present in these four samples i.e. calcium oxide, silicon dioxide, aluminium oxide, iron oxide, sulphur trioxide and magnesium oxide. According to the American Society for Testing and Materials Cement (ASTM C150), the percentage of these oxides, loss on ignition and insoluble residue of these four plants are within the specified quality control range. The present study compared the quality of different oxides at the Portland cement brands in Pakistan. The percentages of SiO₂,SO₃, CaO, Al₂O₃,MgO and Fe₂O₃ were calculated according to American Society for Testing and Materials (ASTM C150) uniform standards. The percentages of all of the brands were within the limits specified by the standard (ASTM C150).

New fluorine-substituted polyfunctional pyrimido-[1,2-b]-[1,2,4]triazines and [1,3,5]-triazino[1,2-b]-[1,2,4]triazines were synthesized via the reaction between 3-amino-6-(2-aminophenyl)-1,2,4-triazin-5(2H)-one with polyfunctional oxygen/sulfur/nitrogen reagents under different conditions. Structures of the target compounds were deduced by elemental analysis and spectral measurements (IR, ¹H/¹³C NMR, and mass spectra). According to the obtained inhibitor assay results, the inhibition activity of the new fluorine-substituted 1,2,4-triazines toward CDK2 decreased in the order of compounds 3 > 8 > 9 > 6 > 13 > 15.

A facile and highly efficient FeF₃-catalyzed method has been developed for the direct synthesis of functionalized dihydropyrimidines from readily available starting materials via Biginelli reaction. These reactions proceed at low-catalyst loadings with high functional group tolerance under mild conditions. This method provides efficient reusability of the catalyst and good to excellent yields of the products, making the protocol more attractive, economical, and environmentally benign. FeF₃ is an attractive catalyst for the Biginelli reaction because of its high acidity, thermal stability and water tolerance.

The experiment was conducted on alfalfa seeds that were brought from Marjajah in the city of Touggourt. After the traditional extraction process, some of its physical properties were measured, including, refractive index, pH, with a yellowish green color, odor, prick, and transport value of 363 cm/S and on blood clotting. The results showed that the seed extract of alfalfa has an effect on blood clotting on the internal and external pathway by the prothrombin rate (TP) obtained that sample 1 has the largest clotting time of 22 seconds and by the time of cefalin kaolin (TCK), the highest coagulation time for sample 2 by 46 seconds. The prothrombin rate and the time of cefalin kaolin chronometer tests also show that alfalfa seed extract exercises an important anticoagulant activity compared to the two coagulation methods, because this activity is more pronounced towards the internal pathway that the external pathway passes, that is, the alfalfa seed extract is better than the normal witness and less than the positive witness heparin.

Metal-organic frameworks (MOFs) are a new class of nanoporous materials that have attracted much attention for the adsorption of small molecules, due to the large size of the cavities. In this study, we investigate the adsorption and diffusion of hydrogen (H₂) and carbon monoxide (CO) guest molecules to the UiO-66 framework, as one of the most widely used MOFs, by using Monte Carlo simulation method. The results prove that an increment in the temperature decreases the amount of the adsorbed H₂ and CO on the UiO-66 framework. While an enhancement of the pressure increases the amount of the adsorbed H₂ and CO on the UiO-66 framework. Besides, the adsorption of H₂ and CO on UiO-66 is the type I isotherm. The calculated isosteric heat for CO/UiO-66 is slightly higher than that of H₂/UiO-66. The means of square displacement (MSD) value is less for CO molecule; hence, the movement of the guest molecule within the host cavity slows down and the guest molecule travels a shorter distance over a period of time. The guest molecule with higher molecular mass possesses less mobility, and therefore, it will have less permeability.

Quinoline and benzofuran moieties are commonly used for the synthesis of therapeutically beneficial molecules and drugs since they possess a wide range of pharmacological activities including potent anticancer activity as compared to other heterocyclic compounds. Many of well-known antimalarial, antimicrobial, anti-helminthic, analgesic, anti-inflammatory, antiprotozoal, and antitumor compounds contain quinoline/benzofuran skeleton. The aim of this study was to analyze ten new quinoline and eighteen benzofuran derivatives for carcinoma cell line growth inhibition and to predict possible interactions with the target. The anticancer activity of these compounds against colon cancer (HCT-116) and triple-negative breast cancer (MDA-MB-468) cell lines was determined and performed molecular docking to predict the possible interactions. Among ten quinoline derivatives, Q1, Q4, Q6, Q9, and Q10 were found to be the most potent against HCT-116 and MDA-MB-468 with IC₅₀ values ranging from 6.2-99.6 and 2.7-23.6 μM, respectively. Using the IC₅₀ values, a model equation with quantitative structure activity relationship (QSAR) was generated with their descriptors such as HBA1, HBA2, kappa (1, 2 and 3), Balaban index, Wiener index, number of rotatable bonds, log S, log P and total polar surface area (TPSA). The effect of benzofuran derivatives was moderate in cytotoxicity tests and hence only quinolines were considered for further analysis. The molecular docking indicated the mammalian / mechanistic target of rapamycin (mTOR), Topoisomerase I and II as possible targets for these molecules. The predicted results obtained from QSAR and molecular docking analysis of quinoline derivatives showed high correlation in comparison to the results of the cytotoxic assay. Overall, this study indicated that quinolines are more potent as anticancer agents compared to benzofurans. Further, compound Q9 has emerged as a lead molecule which could be the base for further development of more potent anticancer agents.

The use of computational chemistry as an effective means of designing eco-friendly organic corrosion inhibitors has been greatly enhanced by the development of Density Functional Theory (DFT). In this study, the inhibitory activity of four antiretroviral drugs, namely, lamivudine, emtricitabine, didanosine and stavudine, was analyzed by this theory. The quantum chemical parameters/descriptors calculated using DFT at B3LYP/6-31G(d) level were used to explain the mechanism of electron transfer between the inhibitors and the copper surface. The results showed that these compounds adsorb on copper surface. It is important to consider the effect of films formed by the adsorption products. In addition, the Fukui functions and the dual descriptor were used as indicators to locate the electrophilic and nucleophilic attack sites within each compound. Finally, the DFT has enabled to accurately predict the adsorption properties and the good inhibition performance of the molecules in the solution studied.

N-Benzyl-4-methylbenzenesulfonamides were prepared via a two-step synthetic process involving the treatment of 4-methylbenzenesulfonyl chloride with a primary amine to give the corresponding 4-methylbenzenesulfonamide. Benzylation of the sulfonamide affords the substituted N-benzyl-4-methylbenzenesulfonamides. The similarities between the two steps of synthesis lend credence to the development of a one-pot synthesis of substituted N-benzyl-4-methylbenzenesulfonamides from 4-methylbenzenesulfonyl chloride. This method was applied to the synthesis of N-allyl-N-benzyl-4-methylbenzenesulfonamide and characterized through spectroscopic and crystallographic means. The crystal structure of N-allyl-N-benzyl-4-methylbenzenesulfonamide was obtained by single-crystal X-ray diffraction. The crystal structure reveals an orthorhombic Pna2₁ space group with cell parameters a = 18.6919 (18) Å, b = 10.5612 (10) Å, c = 8.1065 (8) Å, V = 1600.3 (3) ų and Z = 4, T = 173.15 K, μ(MoKα) = 0.206 mm^-1, Dcalc = 1.251 g/cm³, 14455 reflections measured (4.36° ≤ 2Θ ≤ 54.96°), 3619 unique (R_int = 0.0439, R_sigma = 0.0429) which were used in all calculations. The final R₁ was 0.0428 (I > 2σ(I)) and wR₂ was 0.1079 (all data). Molecules are linked through C-H···N hydrogen bonds and C-H···π interactions.

The title compound, tetra(µ-2-3-(2-oxybenzylideneamino)-1-hydroxypropan-2-olato)-4-nitrophenolatedi-cobalt(III)-di-iron(III) dimethylsulfoxidehexasolvate, crystallizes in the monoclinic space group P2₁/c and represent the first example of heterometallic Co^III-Fe^III complex with 3-((5-nitro-2-hydroxybenzylidene)amino)propane-1,2-diol/2-(((2,3-dihydroxy propyl)iminio)methyl)-4-nitrophenolate) - a hydroxyl rich Schiff base ligand which was obtained in situ. Crystal data for C₅₂H₇₄Cl₂Co₂Fe₂N₈O₂₆S₆ (M = 1720.01 g/mol): monoclinic, space group P2₁/c (no. 14), a = 16.353(3) Å, b = 15.234(2) Å, c = 15.201(3) Å, β = 113.99(2)°, V = 3460.0(12) Å³, Z = 2, T = 173(2) K, μ(MoKα) = 1.225 mm^-1, Dcalc = 1.651 g/cm³, 14130 reflections measured (5.7° ≤ 2Θ ≤ 57.266°), 7748 unique (R_int = 0.1051, R_sigma = 0.2148) which were used in all calculations. The final R₁ was 0.0914 (I > 2σ(I)) and wR₂ was 0.2279 (all data). The metal ions have distorted octahedral coordination geometry and are joined in a tetranuclear {Co₂Fe₂(µ-O)₆} core by O-bridging atoms from the ligand. There are numerous intermolecular interactions occurring between the components of the crystal: π-hole interaction between NO₂···NO₂ groups of the ligands, short S···S, O···O and C··· C interactions and weak and strong hydrogen bonds.

The structure of the title compound, 4-(dimethylamino)pyridin-1-ium-2,5-dichloro-3,6-dioxocyclohexa-1,4-diene-1,4-bis(olate) 4-dimethylaminopyridine water undeca-solvate, C₅₇H₈₇Cl₅N₁₂O₂₁, obtained from interaction between chloranilic acid (caH₂), and dimethyl aminopyridine (DMAP) has been determined by single crystal X-ray diffraction. The title compound, (DMAPH)₅(ca)_2.5·(DMAP)·11H₂O, crystallized in the triclinic crystal system with space group, P  (no. 2), a = 13.3824(15) Å, b = 13.4515(17) Å, c = 19.048(2) Å, α = 86.014(4)°, β = 88.821(4)°, γ = 86.367(4)°, V = 3413.3(7) ų, Z = 2, T = 100(2) K, μ(MoKα) = 0.294 mm^-1, Dcalc = 1.414 g/cm³, 59413 reflections measured (3.76° ≤ 2Θ ≤ 56°), 16405 unique (R_int = 0.0517, R_sigma = 0.0589) which were used in all calculations. The final R₁ was 0.0460 (I ≥ 2σ(I)) and wR₂ was 0.1271 (all data). Using supramolecular chemistry principles, proton donors (chloranilic acid) and acceptor (DMAP) were combined to generate a multicomponent hydrogen-bonded system. Due to the presence of protonated bases (DMAPH⁺), the dominant interactions are the N⁺-H···O hydrogen bonds, whereas the negative charges of an acceptor from the chloranilate dianion (ca^2-) are delocalized. Additionally, three sets of water clusters in the title compound were identified, namely a cyclic pentamer, a linear, and an acute-shaped trimer water cluster. It was further observed that strong hydrogen bond interactions occurred between the solvated aqua molecule(s) acting as a proton donor and the neutral DMAP acting as a proton acceptor. The crystal packing is further stabilized by O-H···Cl and C-H···Cl weak halogen interactions. The lattice metric strength is further held by observed π-π stacking interactions (centroid-centroid) with inter centroid distances between sets of the DMAPH rings of 3.624(3), 3.642(4), 3.739(3), 3.863(3) and 3.898(3) Å, respectively.