Vol 13, No 2 (2022)

June 2022

Table of Contents


Hakan Arslan
DOI 10.5155/eurjchem.13.2.i-ii.2290
Editorial Board
Hakan Arslan
DOI 10.5155/eurjchem.13.2.iii-vi.2291
Graphical Contents

Research Article

Ruchika Sharma, Sandeep Ashok Sankpal, Pradeep Jangonda Patil, Saminathan Murugavel, Sonachalam Sundramoorthy, Rajni Kant
DOI 10.5155/eurjchem.13.2.135-144.2225

2-Amino-4-(2, 5-dimethoxyphenyl)-4a,5,6,7-tetrahydronaphthalene-1,3,3(4H)-tricarbonitrile has been synthesized and characterized by conventional spectroscopic techniques (FT-IR and 1H NMR) and the three-dimensional structure elucidated by single crystal X-ray diffraction studies (SC-XRD). It exists in monoclinic crystal system with space group P21/c and lattice parameters: a = 14.641(13) Å, b = 8.653(4) Å, c = 16.609(10) Å, β = 116.34(3)°, and Z = 4. In the crystal packing, molecules are connected through N-H···O and N-H···N intermolecular and intramolecular C-H···O interactions. The N1-H11···N2 interaction results in the formation of a dimer corresponding to R22(12) graph-set motif. The molecular structure has been theoretically optimized by using density functional theory (DFT) with the basis set B3LYP/6-311G (d,p). The optimized bond geometry shows consistency with the SC-XRD data. Besides this, the molecular electrostatic potential (MEP), Mulliken charges, and frontier molecular orbital analysis have been described. The dnorm, shape index, curvedness, crystal voids, 2D fingerprint (FP) plots, and 3D energy frameworks using Hirshfeld surface (HS) studies have also been computed and investigated. The molecular docking studies for 2-amino-4-(2, 5-dimethoxyphenyl)-4a,5,6,7-tetrahydronaphthalene-1,3,3(4H)-tricarbonitrile with DNA gyrase/lanosterol 14α-demethylase suggest that the compound may act as an active antimicrobial drug.

Brock Anton Stenfors, Felix Nyuangem Ngassa
DOI 10.5155/eurjchem.13.2.145-150.2279

Arylsulfonates are a useful class of synthetic precursors, affording either their arylamine or arylsulfonamide counterparts upon amination via regioselective C–O/S–O bond cleavage. Herein, the synthesis of 2,4-dinitrophenyl 2,4,6-trimethylbenzenesulfonate is described, utilizing our previously developed synthetic methods, and crystallographic characterization. While the mechanism for nucleophilic substitution at the sulfonyl group remains largely unknown, experimental work within our group and in the literature lend credence to a mechanism analogous to its carbonyl counterpart. Characterization of the molecular structure of the title compound, C15H14N2O7S, at 173 K, features a sulfonate group with S=O bond lengths of 1.4198(19) and 1.4183(19) Å and a S–O bond length of 1.6387(18) Å. Viewing down the S–O bond reveals gauche oriented aromatic rings. Crystal data for C15H14N2O7S: Monoclinic, space group P21/c (no. 14), a = 6.8773(10) Å, b = 8.9070(14) Å, c = 25.557(4) Å, β = 93.0630(18)°, V = 1563.3(4) Å3, Z = 4, T = 173.15 K, μ(MoKα) = 0.251 mm-1, Dcalc = 1.557 g/cm3, 12259 reflections measured (3.192° ≤ 2Θ ≤ 50.682°), 2861 unique (Rint = 0.0493, Rsigma = 0.0419) which were used in all calculations. The final R1 was 0.0457 (I > 2σ(I)) and wR2 was 0.1306 (all data).

Parashuram Gudimani, Samundeeswari Lokesh Shastri, Varsha Pawar, Nagashree Uday Hebbar, Lokesh Anand Shastri, Shrinivas Joshi, Shyam Kumar Vootla, Sheela Khanapure, Vinay Sunagar
DOI 10.5155/eurjchem.13.2.151-161.2220

Beta-aryl keto hexanoic acids (5a-l) were synthesized efficiently, followed by esterification that afforded beta-aryl keto methylhexanoates (6a-l). The chemo-selective ketoxime beta-aryl methyl hexanoates (7a-l) were isolated in good yields. Spectroscopic methods were used to characterize the obtained moieties. The antioxidant, anti-inflammatory, and antibacterial properties of the effectively synthesized compounds 7a-l were also investigated. The anti-inflammatory activity of the compounds 7c, 7f, 7i, and 7l was excellent, with a low IC50 value at micromolar concentration, which was much better than the reference diclofenac. All synthesized compounds 7a-l were assessed for their in vitro antibacterial activity against S. aureus, B. subtilis and E. coli.  Most of the compounds exhibited promising activity against Gram-positive bacterial strain, compound 7i showed excellent activity compared to standard streptomycin and in the case of E. coli, compounds 7b, 7c, 7j, 7k and 7l have shown moderate activity. Further, the cytotoxic activities of the compounds were assessed against lung cancer cells (A549) by using MTT assay. The possible interaction mechanism of the molecules 7c and 7g with Gram-negative strain E. coli DNA gyrase B in complex with PDB ID: 4DUH was studied.

Samreen Zahra, Saboora Qaisa, Asma Sheikh, Hamim Bukhari, Chaudhry Athar Amin
DOI 10.5155/eurjchem.13.2.162-167.2231

This study reports the base-catalyzed aqueous sol-gel synthesis of zinc oxide nanoparticles. The solution was primarily comprised of zinc nitrate hexahydrate as a metal precursor, isopropyl alcohol and water as solvents, and glycerin as a stabilizing agent. The effect of calcination temperature on the structure and morphology of the prepared nanoparticles was investigated by varying the calcination temperature from 500 to 900 °C. The X-ray diffraction analysis, infrared spectroscopy, thermogravimetric analysis, and field emission scanning electron microscopy were employed to determine the crystal structure, surface functional groups, thermal stability, and surface morphology of the nanoparticles. The particle size was found to be directly proportional to the calcination temperature.

Evrim Arslan, Ivan Bernal, Roger Lalancette
DOI 10.5155/eurjchem.13.2.168-171.2278

A toluene reaction of vanadyl bis(acetylacetonate) with 1,3,5-triazine produces a symmetrical three-fold hydrolytic cleavage of the triazine, and these three formamide moieties are found in the crystal structure. One of the resulting formamides attaches itself to the sixth (axial) position of the vanadyl complex, producing materials in which the remaining two formamides are trapped in the resulting lattice. Those crystals belong in space group Pca21, Z = 4 and the final R-factor = 0.030 for 3213 data collected at 100 K.

Kodjo Djidjole Etse, Koffi Senam Etse, Marie-Luce Akossiwoa Quashie
DOI 10.5155/eurjchem.13.2.172-179.2271

This work reports for the first time, the analysis of intermolecular interactions in crystal structures of auxin (Indole-3-acetic acid) crystallized as pure sample (Aux-A) or co-crystallized with transport inhibitor response 1 (Aux-B). Using crystal packing of pure auxin and a cluster of residues in a radius of 6 Å around this ligand in the transport inhibitor response 1 binding domain, various properties were calculated and mapped on the Hirshfeld surface (HS). The HSs of the two molecules are characterized by close parameters of volume, area, globularity, and asphericity revealing the efficiency of the considered cluster. The HS mapped over descriptors like de, di and dnorm showed red spots corresponding to hydrogen bonds contacts. In addition to the shape index and curvedness descriptors, the results highlight weak interactions stabilizing the auxin structures. The analyses of electrostatic potential, electron density, and deformation density maps confirm the slightly change in the electron donor and acceptor groups localization. Furthermore, the molecular fingerprint analyses revealed a notable discrepancy in the shape and percentage value of the various contacts. Decomposition of the fingerprint shows that the contributions of important contacts (H···H, H···O, and O···O) are higher in Aux-B than in Aux-A. Finally, the quantitative approach by the determination of the molecular interaction energies of the two structures in their respective crystallographic environment revealed that Aux-A is slightly more stabilized than Aux-B.

Balaji Nagarajan, Gunasekar Manoharan, Ganapathy Narayanan Shanmugam, Nataraj Palaniyappan, Abhinav Yarragunta
DOI 10.5155/eurjchem.13.2.180-185.2252

Effective chromatographic separation was achieved on a phenyl-hexyl stationary phase (50×2.1 mm, 1.9 micron particles) with the economical and straightforward mobile phase combination delivered in isocratic mode at a flow rate of 0.6 mL/min at 254 nm using a ultra-performance liquid chromatography (UPLC) system. In the developed method, the resolution between molindone and its related compounds was more significant than 2.0. Regression analysis shows an r2 value (correlation coefficient) greater than 0.999 for molindone and its associated compounds. This method could detect related compounds of molindone at a level below 0.009% with respect to a test concentration of 500 µg/mL for a 2.0 µL injection volume. The method has shown good, consistent recoveries for related compounds (90-110%). The test solution was found to be stable in the diluent for 48 hours. The drug was subjected to stress conditions. The mass balance was found to be close to 99.3%.

Chad Miller, Steven Schildcrout, Howard Mettee, Ganesaratnam Balendiran
DOI 10.5155/eurjchem.13.2.186-195.2275

1H- and 13C-NMR chemical shifts were measured for four fibric acids (bezafibrate, clofibric acid, fenofibric acid, and gemfibrozil), which are lipid-lowering drugs. Correlation is found with DFT-computed chemical shifts from the conformational analysis. Equilibrium populations of optimized conformers at 298 K are very different when based on computed Gibbs energies rather than on potential energies. This is due to the significant entropic advantages of extended rather than bent conformational shapes. Abundant conformers with intramolecular hydrogen bonding via five-member rings are computed for three fibric acids, but not gemfibrozil, which lacks suitable connectivity of carboxyl and phenoxy groups. Trends in computed atom-positional deviations, molecular volumes, surface areas, and dipole moments among the fibric acids and their constituent conformations indicate that bezafibrate has the greatest hydrophilicity and fenofibric acid has the greatest flexibility. Theoretical and experimental comparison of chemical shifts of standards with sufficient overlap of fragments containing common atoms, groups, and connectivity may provide a reliable minimal set to benchmark and generate leads.

Cheikh Ndoye, Gregory Excoffier, Gorgui Awa Seck, Ousmane Diouf, IbraIbrahima Elhadji Thiam, Mamadou Sidibe, Mohamed Gaye
DOI 10.5155/eurjchem.13.2.196-205.2253

The reactions of Schiff base 1-(1-hydroxypropan-2-ylidene)thiosemicarbazide (H2L), with salt of thiocyanate metal (II) (Co, Ni, or Zn), provided one dinuclear and two new mononuclear complexes, formulated respectively as {[Co(LH)2]2·[Co(NCS)4] ·2(MeOH)} (1), {[Ni(H2L)2]·[(NCS)2]} (2) and [Zn(H2L)(NCS)2] (3). These compounds have been studied and characterized by elemental analysis, infrared, and ultraviolet-visible (UV-vis) spectroscopies. The structures of the three complexes have been resolved by X-ray crystallography technique. The dinuclear complex 1 crystallizes in the orthorhombic space group Fdd2 with the following unit cell parameters a = 33.1524 (3) Å, b = 19.3780 (2) Å, c = 13.2533 (2) Å, V = 8514.28 (17) Å3, Z = 16, R1 = 0.025 and wR2 = 0.063, the mononuclear complex 2 crystallizes in the monoclinic space group P21/n with the following unit cell parameters a = 11.5752 (1) Å, b = 12.3253 (1) Å, c = 14.2257 (2) Å, β = 106.855 (1)°, V = 1942 (4) Å3, Z = 4, R1 = 0.038 and wR2 = 0.106 and  the mononuclear complex 3 crystallizes in the monoclinic space group P21/c with the following unit cell parameters a = 6.1121 (2) Å, b = 26.8272 (7)  Å, c = 8.0292 (2) Å, β = 99.876 (3)°, V = 1297.04 (6) Å3, Z = 4, R1 = 0.026 and wR2 = 0.057. The asymmetric unit of Complex 1 contains one cationic unit in which the ligand acts in its monodeprotonated form in tridentate fashion and one half of the anionic unit containing two thiocyanate co-ligands. In complexes 2 and 3, the ligand acts in its neutral form in a tridentate manner. In complex 2, two ligand molecules coordinate the Ni(II) center, and the thiocyanate moieties remains uncoordinated. In complex 3, the Zn(II) is coordinated by one ligand molecule and two thiocyanate groups through their nitrogen atoms. Numerous hydrogen bonds consolidated the structures of complexes 1, 2, and 3 in a three-dimensional network.

Bubun Banerjee, Varun Sharma, Aditi Sharma, Gurpreet Kaur, Vivek Kumar Gupta
DOI 10.5155/eurjchem.13.2.206-213.2234

The co-crystal of 2-aminobenzothiazol with 4-fluorobenzoic acid were synthesized and characterized by elemental analyses, spectral studies (FT-IR, NMR, HRMS) and single-crystal X-ray diffraction analysis. This compound co-crystallizes in the monoclinic space group P21/c (no. 14), a = 11.7869(14) Å, b = 4.0326(5) Å, c = 27.625(3) Å, β = 92.731(10)°, = 1311.6(3) Å3, Z = 4, T = 293(2) K, μ(CuKα) = 2.345 mm-1, Dcalc = 1.470 g/cm3, 3568 reflections measured (7.508° ≤ 2Θ ≤ 134.202°), 2280 unique (Rint = 0.0262, Rsigma = 0.0413) which were used in all calculations. The final R1 was 0.0446 (I > 2σ(I)) and wR2 was 0.1274 (all data). The crystal structure is stabilized by elaborate system of N–H···O and O-H···O hydrogen bonds to form supramolecular structures. Furthermore, the 3D Hirshfeld surfaces and the associated 2D fingerprint plots have been analyzed for molecular interactions.

Hind Ali Abdullatif, Adel Magdy Michael, Yossra Ahmed Trabik, Miriam Farid Ayad
DOI 10.5155/eurjchem.13.2.214-223.2236

This work describes a comparative study of two multivariate chemometric and univariate spectrophotometric methods for the determination of a ternary drug mixture containing oxytetracycline HCl, bromhexine HCl, and lidocaine HCl. All methods show high sensitivity and similar linearity range. Meanwhile, the chemometric method has the advantage of higher accuracy, higher specificity and better regression parameters. The two spectrophotometric methods are constant multiplication coupled with spectrum subtraction and successive ratio subtraction coupled with spectrum subtraction while the chemometric method used partial least square and principal component regression models. In addition, a spiking technique was used to increase the concentration of bromhexine HCl in the dosage form, allowing its determination despite its low contribution. Methods were successfully applied in the dosage form Oxyclear® veterinary injection in pure powder as well as in its pharmaceutical formulation. Statistical comparison showed no significant difference between the developed methods and the reference method.

Mohammad Suhail
DOI 10.5155/eurjchem.13.2.224-229.2237

Different conformers of many aliphatic compounds such as ethane, butane, cyclohexane and their derivatives have been studied to find the most reactive as well as the most stable conformer. For the first time, two conformers of p-xylene were found using theoretical DFT calculation and the vibrational modes, Raman activity, and other spectra of each conformer were also studied. The most significant data that clearly distinguished both conformers was depolarization spectra. Besides, many other parameters were found different in both conformers of p-xylene such as Mulliken charge’s, optimization energy, HOMO’s of both conformers. Also, the presented study predicts, why eclipsed conformer of p-xylene is more reactive than staggered conformer. The reactivity of the eclipsed form is explained on the basis of HOMO-LUMO energy gap. Also, the presented study opens the door for future work to be done because each conformer can produce a specific product. Moreover, the rates of reaction are also dependent on the conformers and their relative stability.

Tahir Mehmood, Bhumiben Chandubhai Patel, Jayarama Prakasha Reddy
DOI 10.5155/eurjchem.13.2.230-233.2256

A 1:1 co-crystal of phenazine and phenothiazine was prepared. The crystal structure was determined by using a single crystal X-ray crystallography technique. Analysis of the crystal revealed that the molecular complex crystallizes in monoclinic P21/n space group, C12H8N2·C12H9NS, a = 9.068(2) Å, b = 8.872(2) Å, c = 23.935(4) Å, β = 92.16(4)°, = 1924.1(6) Å3, Z = 4, T = 293(2) K, μ(MoKα) = 0.182 mm-1, Dcalc = 1.310 g/cm3, 8057 reflections measured (3.4° ≤ 2Θ ≤ 46.54°), 2751 unique (Rint = 0.0559, Rsigma = 0.0618) which were used in all calculations. The final R1 was 0.0548 (>2sigma(I)) and wR2 was 0.1029 (all data). The molecules recognize each other through N-H···N and C-H···N hydrogen bonds, thus producing a tetramer unit. These units further interact with one another via C-H···S hydrogen bonds.

Nilankar Diyali, Meena Chettri, Abhranil De, Bhaskar Biswas
DOI 10.5155/eurjchem.13.2.234-240.2265

Hydrazine functionalized Schiff base, 1,2-di(benzylidene)hydrazine has been synthesized through a condensation between hydrazine and benzaldehyde under reflux, and structurally characterized. The crystal structure analysis reveals that the Schiff base crystallizes in an orthorhombic crystal system with the Pbcn space group. Crystal data for C14H12N2: a = 13.130(2) Å, b = 11.801(2) Å, c = 7.5649(16) Å, = 1172.1(4) Å3, Z = 4, T = 298.0(2) K, μ(MoKα) = 0.071 mm-1, Dcalc = 1.180 g/cm3, 10252 reflections measured (6.206° ≤ 2Θ ≤ 65.352°), 2027 unique (Rint = 0.0381, Rsigma = 0.0283) which were used in all calculations. The final R1 was 0.0627 (I > 2σ(I)) and wR2 was 0.2462 (all data). It is evident that the imine protons are intramolecularly locked with the imine-N bond, and the phenyl rings exist in anti orientation with respect to the =N-N= bond adopting a nearly planar conformation. The Schiff base grows a one-dimensional framework in the crystalline phase through long-distant C-H···π interaction. Hirshfeld surface and energy framework analyses have also been performed to understand the supramolecular forces and their contributions meticulously. The hydrazine functionalized Schiff base showed an excellent antidiabetic activity through α-amylase inhibitory assay relative to a standard compound, acarbose under an identical condition.


Review Article

Nesrin Mahmoud Morsy, Ashraf Sayed Hassan
DOI 10.5155/eurjchem.13.2.241-252.2245

Considering the essential biological and medicinal properties of chalcones, the synthesis of these compounds has attracted the interest of medicinal and organic chemists. This review aims to describe the different strategies developed so far for the synthesis of chalcones and their applications. After a brief introduction of the chalcones and their biological activities, different synthetic approaches such as chemical and other methods are described and organized on the basis of the catalysts and the other reagents employed in the syntheses. Some of the reactions have been applied successfully to the synthesis of biologically important compounds. Moreover, the biological and pharmacological activities of chalcones have been shown.