Intermolecular interactions play a vital role in crystal structures. Therefore, we conducted a topological study, using Hirshfeld surfaces and atom in molecules (AIM) analysis, to decompose and analyze, respectively, the different intermolecular interactions in six hydrazone-diacetyl platinum(II) complexes. Using AIM and natural bond orbital (NBO) analyses, we determined the type, nature, and strength of the interactions. All the studied complexes contain C-H⋯O interactions, and the presence of bond critical points along the intermolecular paths underlines their significance. The electron densities (ρ(r)) at the bond critical points (0.0031–0.0156 e/a₀³) fall within the typical range for H-bonding interactions. Also, the positive values of the Laplacian of the electron density (∇²ρ(r)) revealed the depletion of electronic charge on the interatomic path, another characteristic feature of closed-shell interactions. The ratios of the absolute potential energy density to the kinetic energy density (|V(r)|/G(r)) and ρ(r) are highest for the O2⋯H15-N3 interaction in [Pt(COMe)₂(2-pyCMe=NNH₂)] (1); hence, this interaction has the highest covalent character of all the O⋯H intermolecular interactions. Interestingly, in [Pt(COMe)₂(H₂NN=CMe-CMe=NNH₂)] (3), there are significant N-H⋯Pt interactions. Using the NBO method, the second-order interaction energies, E⁽²⁾, of these interactions range from 3.894 to 4.061 kJ/mol. Furthermore, the hybrid Pt orbitals involved in these interactions are comprised of d_xy, d_xz, and s atomic orbitals. Full article

A one-pot reaction was described that results in various pyrazole-thiobarbituric acid derivatives as new pharmacophore agents. These new heterocycles were synthesized in high yields with a broad substrate scope under mild reaction conditions in water mediated by NHEt₂. The molecular structures of the synthesized compounds were assigned based on different spectroscopic techniques. The new compounds were evaluated for their antibacterial and antifungal activity. Compounds 4h and 4l were the most active compounds against C. albicans with MIC = 4 µg/L. Compound 4c exhibited the best activity against S. aureus and E. faecalis with MIC = 16 µg/L. However, compounds 4l and 4o were the most active against B. subtilis with MIC = 16 µg/L. Molecular docking studies for the final compounds and standard drugs were performed using the OpenEye program. Full article

5-[(3-Fluorophenyl)(2-hydroxy-6-oxocyclohex-1-en-1-yl)-methyl]-6-hydroxy-1,3-di-methylpyrimidine-2,4(1H,3H)-dione 3 was synthesized via a multicomponent reaction. The Aldol–Michael addition reactions of N,N-dimethylbarbituric acid, cyclohexane-1,3-dione, and 3-fluorobenzaldehyde in aqueous solution gave the product in high yield. The molecular structure of the compound was confirmed by spectroscopic methods and X-ray crystallography. The title compound (C₁₉H₁₉FN₂O₅·H₂O) crystallizes in the Monoclinic form, P2₁/c, a = 7.8630 (5) Å, b = 20.0308 (13) Å, c = 11.3987 (8) Å, β = 104.274 (3)°, V = 1739.9 (2)° ų, Z = 4, R_int = 0.117, wR(F²) = 0.124, T = 100 K. Full article

Reaction of barbituric acid derivatives and di-substituted benzaldehyde in water afforded arylidene-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione derivatives (1 and 2). The one step reaction proceeded efficiently, smoothly, and in excellent yield. The arylidene compounds were characterized by spectrophotometric tools plus X-ray single crystal diffraction technique. Quantum chemical calculations were performed using the DFT/B3LYP method to optimize the structure of the two isomers (1 and 2) in the gas phase. The optimized structures were found to agree well with the experimental X-ray structure data. The highest occupied (HOMO) and lowest unoccupied (LUMO) frontier molecular orbitals analyses were performed and the atomic charges were calculated using natural populationanalysis. Full article

Urease enzyme (EC 3.5.1.5) has been determined as a virulence factor in pathogenic microorganisms that are accountable for the development of different diseases in humans and animals. In continuance of our earlier study on the helicobacter pylori urease inhibition by barbituric acid derivatives, 3D-QSAR (three dimensional quantitative structural activity relationship) advance studies were performed by Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) methods. Different partial charges were calculated to examine their consequences on the predictive ability of the developed models. The finest developed model for CoMFA and CoMSIA were achieved by using MMFF94 charges. The developed CoMFA model gives significant results with cross-validation (q²) value of 0.597 and correlation coefficients (r²) of 0.897. Moreover, five different fields i.e., steric, electrostatic, and hydrophobic, H-bond acceptor and H-bond donors were used to produce a CoMSIA model, with q² and r² of 0.602 and 0.98, respectively. The generated models were further validated by using an external test set. Both models display good predictive power with r²_pred ≥ 0.8. The analysis of obtained CoMFA and CoMSIA contour maps provided detailed insight for the promising modification of the barbituric acid derivatives with an enhanced biological activity. Full article

Successful alkylations of the nitrogen of ethyl indol-2-carboxylate were carried out using aq. KOH in acetone. The respective N-alkylated acids could be obtained without separating the N-alkylated esters by increasing the amount of KOH and water. The use of NaOMe in methanol led to transesterification instead of the alkylation, while the use of NaOEt led to low yields of the N-alkylated acids. Hydrazinolysis of the ester gave indol-2-carbohydrazide which then was allowed to react with different aromatic aldehydes and ketones in ethanol catalyzed by acetic acid. Indol-2-thiosemicarbazide was used in a heterocyclization reaction to form thiazoles. The new structures were confirmed using NMR, mass spectrometry and X-ray single crystal analysis. Full article

A novel thiophene-containing compound, 2-acetyl-3-amino-5-[(2-oxopropyl)sulfanyl]-4-cyanothiophene (4) was synthesized by reaction of malononitrile with CS₂ in the presence of K₂CO₃ under reflux in DMF and the subsequent reaction with chloroacetone followed by cyclization. This compound has been characterized by means of FT-IR, ¹H-NMR, ¹³C-NMR, and mass spectrometry as well as elemental analysis. In addition, the molecular structures of compound 4 was determined by X-ray crystallography. The geometry of the molecule is stabilized by an intramolecular interaction between N1–H1···O1 to form S6 graf set ring motif. In the crystal, molecules are linked via N1–H2···O1 and C7–H7A···N2 interactions to form a three-dimensional network. Molecular structure and other spectroscopic properties of compound 4 were calculated using DFT B3LYP/6-31G (d,p) method. Results revealed a good agreement between the optimized geometric parameters and the observed X-ray structure. Furthermore, and by employing the natural bond orbital (NBO) method, the intramolecular charge transfer (ICT) interactions along with natural atomic charges at different sites, were calculated; results indicated strong n→π* ICT from LP(1)N5→BD*(2)C15-C16 (63.23 kcal/mol). In addition, the stabilization energy E(2) of the LP(2)O3→ BD*(1)N5-H6 ICT (6.63 kcal/mol) indicated the presence of intramolecular N-H···OH bonding. Similarly, calculations of the electronic spectra of compound 4 using, TD-DFT revealed a good agreement with the experimental data. Finally, compound 4 was evaluated for its in vitro cytotoxic effect against PC-3 and HeLa cell lines, as an anticancer agent, and found to be nontoxic. Full article

Alkylated, benzylated and bromoalkylated benzimidazole-thione that intramolecularly heterocyclized to 3,4-dihydro-2H-[1,3]thiazino[3,2-a]benzimidazole were synthesized. The chemical structure of the synthesized product was characterized by Infra Red, ¹H-NMR, ¹³C-NMR, and Mass spectroscopy. Furthermore, the molecular structures of 8 and 9 were confirmed by X-ray single crystallography in different space groups, Pbca and P2₁/c, respectively. Full article

The synthesis of the new diethyl ammonium salt of diethylammonium(E)-5-(1,5-bis(4-fluorophenyl)-3-oxopent-4-en-1-yl)-1,3-diethyl-4,6-dioxo-2-thioxohexaydropyrimidin-5-ide 3 via a regioselective Michael addition of N,N-diethylthiobarbituric acid 1 to dienone 2 is described. In 3, the carboanion of the thiobarbituric moiety is stabilized by the strong intramolecular electron delocalization with the adjacent carbonyl groups and so the reaction proceeds without any cyclization. The molecular structure investigations of 3 were determined by single-crystal X-ray diffraction as well as DFT computations. The theoretically calculated (DFT/B3LYP) geometry agrees well with the crystallographic data. The effect of fluorine replacement by chlorine atoms on the molecular structure aspects were investigated using DFT methods. Calculated electronic spectra showed a bathochromic shift of the π-π* transition when fluorine is replaced by chlorine. Charge decomposition analyses were performed to study possible interaction between the different fragments in the studied systems. Molecular docking simulations examining the inhibitory nature of the compound show an anti-diabetic activity with Pa (probability of activity) value of 0.229. Full article

The synthesis of 2,6-bis(hydroxy(phenyl)methyl)cyclohexanone 1 is described. The molecular structure of the title compound 1 was confirmed by NMR, FT-IR, MS, CHN microanalysis, and X-ray crystallography. The molecular structure was also investigated by a set of computational studies and found to be in good agreement with the experimental data obtained from the various spectrophotometric techniques. The antimicrobial activity and molecular docking of the synthesized compound was investigated. Full article

Ethyl 5-acetyl-4-methyl-2-(phenylamino)thiophene-3-carboxylate (2) and there derivatives 3a–c, 4, 6a–c and 9a–f were synthesized. The structure of compound 2 was deduced by ¹H-NMR, ¹³C-NMR, FT-IR, MS, microanalysis, and single-crystal X-ray crystallography. The compound crystallized in the monoclinic system, with space group P2₁/c and cell coordinates a = 8.5752(16) Å, b = 21.046(4) Å, c = 8.2941(12) Å, β = 101.131(6)°, V = 1468.7(4) ų, and Z = 4. Compounds 2, 3a–c, 4, 5a–c and 9a–f were subjected into in vitro antimicrobial activity tests. Compounds 3a and 3c were more potent than standard drug amphotericin B, showing MIC values of 23.8 ± 0.42 and 24.3 ± 0.68, respectively, against Aspergillus fumigatus while the standard drug MIC was 23.7 ± 0.1. Compound 3c was also more potent (MIC 24.8 ± 0.64) than the standard drug amphotericin B (MIC 19.7 ± 0.2) against Syncephalastrum racemosum. Compounds 4 and 9f also showed promising anti-microbial activity. Molecular modeling was performed for the most active compounds. Full article

This paper describes an efficient and regioselective method for the synthesis of novel fluorinated spiro-heterocycles in excellent yield by cascade [5+1] double Michael addition reactions. The compounds 7,11-bis(4-fluorophenyl)-2,4-dimethyl- 2,4-diazaspiro[5.5] undecane-1,3,5,9-tetraone (3a) and 2,4-dimethyl-7,11-bis (4-(trifluoromethyl)phenyl)-2,4-diazaspiro[5.5]undecane-1,3,5,9-tetraone (3b) were characterized by single-crystal X-ray diffraction, FT-IR and NMR techniques. The optimized geometrical parameters, infrared vibrational frequencies and NMR chemical shifts of the studied compounds have also been calculated using the density functional theory (DFT) method, using Becke-3-Lee-Yang-Parr functional and the 6-311G(d,p) basis set. There is good agreement between the experimentally determined structural parameters, vibrational frequencies and NMR chemical shifts of the studied compounds and those predicted theoretically. The calculated natural atomic charges using NBO method showed higher polarity of 3a compared to 3b.The calculated electronic spectra are also discussed based on the TD-DFT calculations. Full article

Several series of novel substituted thienothiophene derivatives were synthesized by reacting the synthone 1 with different reagents. The newly synthesized compounds were characterized by means of different spectroscopic methods such as IR, NMR, mass spectrometry and by elemental analyses. The new compounds displayed significant activity against both Gram-positive and Gram negative bacteria, in addition to fungi. Molecular docking and POM analyses show the crucial role and impact of substituents on bioactivity and indicate the unfavorable structural parameters in actual drug design: more substitution doesn’t guaranty more efficiency in bioactivity. Full article

An eco-benign synthesis of pyrimidine derivatives 2a,b containing different functional groups with different electronic character starting from nitroalkenes 1a and 2b has been described. The structures for 1a and 2a,b have been characterized by single crystal X-ray diffraction analysis. The thermal data of the molecules pointed towards important structural aspects of their stability. The mechanism of their thermal decomposition is discussed. The thermodynamic parameters of the dissociation steps were evaluated and discussed. DFT calculations reveal that the compound 1a possesses a high calculated dipole moment value (8.28 D) which indicates its high reactivity towards its surrounding molecules. Full article

In this work, synthesis, antimicrobial activities and molecular docking studies of some new series of substituted quinazolinone 2a–h and 3a–d were described. Starting form 2-aminobenzamide derivatives 1, a new series of quinazolinone derivatives has been synthesized, in high yields, assisted by microwave and classical methods. Some of these substituted quinazolinones were tested for their antimicrobial activity against Gram-negative bacteria (Pseudomonas aeruginosa and Esherichia coli) and Gram-positive bacteria (Staphylococcus aureus, and Bacillus subtilis), and anti-fungal activity against (Aspergillus fumigatus, Saccharomyces cervevisiae, and Candida albicans) using agar well diffusion method. Among the prepared products, 3-benzyl-2-(4-chlorophenyl)quinazolin-4(3H)-one (3a) was found to exhibits the most potent in vitro anti-microbial activity with MICs of 25.6 ± 0.5, 24.3 ± 0.4, 30.1 ± 0.6, and 25.1 ± 0.5 µg/mL against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Esherichia coli, respectively. Compound 3a was found to exhibits the most potent in vitro anti-fungal activity with MICs of 18.3 ± 0.6, 23.1 ± 0.4, and 26.1 ± 0. 5 µg/mL against Aspergillus fumigatus, Saccharomyces cervevisiae, and Candidaal bicans, respectively. Full article

In this contribution, two novel supported and non-supported ruthenium(II) complexes of type [RuCl₂(dppme)(NN)] where [dppme is H₂C=C(CH₂PPh₂)₂ and NN is N1-(3-(trimethoxysilyl)propyl)ethane-1,2-diamine] were prepared. The NN co-ligand caused release of one of the dppme ligands from [RuCl₂(dppme)₂] precursor to yield complex 1. The process of substitution of dppme by NN was monitored by ³¹P{¹H}-NMR. Taking advantage of the presence of trimethoxysilane group in the backbone of complex 1, polysiloxane xerogel counterpart, X1, was prepared via sol-gel immobilization using tetraethoxysilane as cross-linker. Both complexes 1 and X1 have been characterized via elemental analysis, CV and a number of spectroscopic techniques including FT-IR, ¹H-, ¹³C-, and ³¹P-NMR, and mass spectrometry. Importantly, carbonyl selective hydrogenation was successfully accomplished under mild conditions using complex 1 as a homogenous catalyst and X1 as a heterogeneous catalyst, respectively. Full article

A series of new 2-aminobenzamide derivatives (1–10) has been synthesized in good to excellent yields by adopting both conventional and/or a time-efficient microwave assisted methodologies starting from isatoic anhydride (ISA) and characterized on the basis of their physical, spectral and microanalytical data. Selected compounds of this series were then tested against various bacterial (Bacillus subtilis (RCMB 000107) and Staphylococcus aureus (RCMB 000106). Pseudomonas aeruginosa (RCMB 000102) and Escherichia coli (RCMB 000103) and fungal strains (Saccharomyces cerevisiae (RCMB 006002), Aspergillus fumigatus (RCMB 002003) and Candida albicans (RCMB 005002) to explore their potential as antimicrobial agents. Compound 5 was found to be the most active compound among those tested, which showed excellent antifungal activity against Aspergillus fumigatus (RCMB 002003) more potent than standard Clotrimazole, and moderate to good antibacterial and antifungal activity against most of the other strains of bacteria and fungi. Furthermore, potential pharmacophore sites were identified and their activity was related with the structures in the solution. Full article

An efficient method for the synthesis of a variety of pyrimidine derivatives 3a–t by reaction of barbituric acids 1a,b as Michael donor with nitroalkenes 2a–k as Michael acceptor using an aqueous medium and diethylamine is described. This 1,4-addition strategy offers several advantages, such as using an economic and environmentally benign reaction media, high yields, versatility, and shorter reaction times. The synthesized compounds were identified by ¹H-NMR, ¹³C-NMR, CHN, IR, and MS. The structure of compound 3a was further confirmed by single crystal X-ray structure determination. Full article

[NiCl₂(C₁₄H₁₂N₂)(H₂O)] complex has been synthesized from nickel chloride hexahydrate (NiCl₂·6H₂O) and 2,9-dimethyl-1,10-phenanthroline (dmphen) as N,N-bidentate ligand. The synthesized complex was characterized by elemental analysis, infrared (IR) spectroscopy, ultraviolet-visible (UV-vis) spectroscopy and differential thermal/thermogravimetric analysis (TG/DTA). The complex was further confirmed by single crystal X-ray diffraction (XRD) as triclinic with space group P-1. The desired complex, subjected to thermal decomposition at low temperature of 400 °C in an open atmosphere, revealed a novel and facile synthesis of pure NiO nanoparticles with uniform spherical particle; the structure of the NiO nanoparticles product was elucidated on the basis of Fourier transform infrared (FT-IR), UV-vis spectroscopy, TG/DTA, XRD, scanning electron microscopy (SEM), energy-dispersive X-ray spectrometry (EDXS) and transmission electron microscopy (TEM). Full article

A simple protocol, involving the green synthesis for the construction of novel bis-pyrimidine derivatives, 3a–i and 4a–e are accomplished by the aqueous diethylamine media promoted tandem Aldol-Michael reaction between two molecules of barbituric acid derivatives 1a,b with various aldehydes. This efficient synthetic protocol using an economic and environmentally friendly reaction media with versatility and shorter reaction time provides bis-pyrimidine derivatives with high yields (88%–99%). Full article

Thioenethiophene derivatives represent an important class of compounds with diverse biological activities. We describe here the synthesis of a new series of thieno[2,3-b]thiophene containing bis-heterocyclic compounds 3–7. All the compounds were evaluated for their in vitro antioxidant potential, α-glucosidase and β-glucuronidase inhibiton and anticancer activity against PC-3 cell lines. Compounds 2b (IC₅₀ = 1.3 ± 0.2 μM), 5a (IC₅₀ = 2.3 ± 0.4 μM) and 5b (IC₅₀ = 8.7 ± 0.1 μM) showed a potent inhibition of β-glucuronidase enzyme, more active than the standard d-saccharic acid 1,4-lactone (IC₅₀ = 45.8 ± 2.5 μM). Compounds 5a (IC₅₀ = 22.0 ± 0.3 μM) and 5b (IC₅₀ = 58.4 ± 1.2 μM) were also found to be potent α-glucosidase inhibitors as compared to standard drug (acarbose, IC₅₀ = 841 ± 1.7 μM). Full article

An efficient and convenient strategy for the enantioselective synthesis of enantiomerically enriched 10-ethyl-7,8-dihydro-γ-ionone isomers (R)-(+)-7, and (S)-(−)-7 are described utilizing a lipase mediated resolution protocol, and reductive elimination of the secondary allylic alcohol as the key step. The enantioselective and diastereoselective lipase kinetic acetylation of 4-hydroxy-γ-ionone derivatives 6a afforded the 4-acetyl-γ-ionone derivatives (−)-8, and the 4-hydrox-γ-ionone derivatives (+)-6a, which are suitable precursors of the desired products. Stereospecific palladium-mediated elimination of allylic acetate provides the target compounds with an excellent enantiomeric excess and yield. Additionally, the novel 4,5-didehydro-α-ionone 13 is obtained from readily prepared (2,6,6-trimethylcyclohexa-2,4-dien-1-yl) methanol 9. The structures of all newly synthesized compounds have been elucidated by ¹H, ¹³C NMR, GC-MS, and IR spectrometry. These compounds represent a new class of odorants that may be of pivotal relevance in industrial perfumery. Full article

The hemilabile chiral C₂ symmetrical bidentate substituted amide ligands (1R,2R)-5_a-d and (1S,2S)-6_a-d were synthesized in quantitative yield from (1R,2R)-(+)-3-methylenecyclo-propane-1,2-dicarboxylic acid (1R,2R)-3 and (1S,2S)-(-)-3-methylene-cyclopropane-1,2-dicarboxylic acid (1S,2S)-3, in two steps, respectively. The chiral Feist’s acids (1R,2R)-3 and (1S,2S)-3 were obtained in good isomeric purity by resolution of trans-(±)-3-methylene-cyclopropane-1,2-dicarboxylic acid from an 8:2 mixture of tert-butanol and water, using (R)-(+)-α-methylbenzyl amine as a chiral reagent. This process is reproducible on a large scale. All these new synthesized chiral ligands were characterized by ¹H-NMR, ¹³C-NMR, IR, and mass spectrometry, as well as elemental analysis and their specific rotations were measured. These new classes of C₂ symmetric chiral bisamide ligands could be of special interest in asymmetric transformations. Full article

This paper reports details about the synthesis of a series of novel functionalized symmetrical bis-heterocyclic compounds containing a thieno[2,3-b]thiophene motif. Bis-thiazole derivatives 2, 3a-c and thiazolo[3,2-a]pyridine derivatives 4a-c are achieved. The hitherto unknown dihydrothiophene derivatives 6a-d via bis-pyridimium salt 5 are obtained. Additionally, the novel hydrazonothieno[2,3-b]thiophene derivatives 10a-c are obtained via bis-tosylacetylthieno[2,3-b]thiophene derivative 9. All compounds are characterized by ¹H-, ¹³C-NMR, GCMS, IR, and UV-vis spectrometry. These compounds represent a new class of sulfur and nitrogen containing heterocycles that should also be of interest as new materials. Full article

The synthesis of several novel chiral phosphoramidite ligands (L1–L8) with C₂ symmetric, pseudo C₂ symmetric secondary amines and chiral Brønsted acids 1a,b has been achieved. These chiral auxiliaries were obtained from commercially available d-mannitol, and secondary amines in moderate to excellent yields. Excellent diastereoselectivites of ten chiral auxiliaries were obtained. The chiral phosphoramidite ligands and chiral Brønsted acids were fully characterized by spectroscopic methods. Full article

A comprehensive and facile method for the synthesis of new functionalized bis-heterocyclic compounds containing a thieno[2,3-b]thiophene motif is described. The hitherto unknown bis-pyrazolothieno[2,3-b]thiophene derivatives 2a–c, bis-pyridazin othieno[2,3-b]thiophene derivatives 4, bis-pyridinothieno[2,3-b]thiophene derivatives 6a,b, and to an analogous bis-pyridinothieno[2,3-b]thiophene nitrile derivatives 7 are obtained. Additionally, the novel bis-pyradazinonothieno[2,3-b]thiophene derivatives 9, and nicotinic acid derivatives 10, 11 are obtained via bis-dienamide 8. The structures of all newly synthesized compounds have been elucidated by ¹H, ¹³C NMR, GCMS, and IR spectrometry. These compounds represent a new class of sulfur and Nitrogen containing heterocycles that should also be of interest as new materials. Full article

A facile and convenient synthesis of some novel hydrazones, schiff’s base and pyrazoles from thieno[2,3-b]thiophene derivatives 1 have been achieved in high yields assisted by microwave and classical methods. The structures of all the title compounds have been elucidated by elemental analysis, IR, MS, ¹H-NMR and ¹³C-NMR. Generally, these findings represent a new class of sulfur and nitrogen moieties that should also be of interest as new materials. Full article

A series of new bis(heterocycles) featuring thieno[2,3-b]thiophene rings was synthesized in a combinatorial manner. Intramolecular cyclization of enaminone derivatives with appropriate N-nucleophiles afforded the target compounds. All compounds were characterized by ¹H-, ¹³C-NMR, GCMS, IR, and UV-Vis spectrometry. These compounds represent a new class of sulfur- and nitrogen-containing heterocycles that should also be of interest as new materials. Full article