Title Compound Research Articles

Design, one-pot novel synthesis of substituted acridine derivatives: DFT, structural characterisation, ADME and anticancer DNA polymerase epsilon molecular docking studies

A novel type of reaction synthesis of an acridine derivative alkaloid of 9-chloro-1-methylacridine-4-carboxylic acid (CMAC) and structurally characterised. FT-IR, 1H NMR, 13C NMR, and GC-mass spectrometry were used. Density functional theory calculations were performed to understand the electronic properties of the molecular structures, including the frontier molecular orbital (FMO), molecular electrostatic potentials (MEP), NLO material properties, RDG studies, and global chemical reactivity descriptors. Furthermore, Theoretical IR, a vibrational wavenumber was obtained for the title compound by simulation and compared with the experimental wavenumbers. Vibrational energy distribution analysis (VEDA) software was used for potential energy decomposition (PED) analysis. Finally, the bioavailability of the title compound was examined by (ADME/Tox) absorption, distribution, metabolism, and excretion properties. DNA polymerase epsilon, which carries a P301R substitution (PDB ID: 6g0a), was used as the receptor for employing an in silico molecular docking process. The docking study revealed the significant interactions between the receptor active sites and the CMAC ligand.

Synthesis, characterization and supra-molecular analysis for (E)-3-(pyridin-4-yl)acrylic acid.

The title compound, C8H7NO2, crystallizes as prismatic colourless crystals in space group P , with one mol-ecule in the asymmetric unit. The pyridine ring is fused to acrylic acid, forming an almost planar structure with an E-configuration about the double bond with a torsion angle of -6.1 (2)°. In the crystal, strong O-H⋯N inter-actions link the mol-ecules, forming chains along the [101] direction. Weak C-H⋯O inter-actions link adjacent chains along the [100] direction, generating an R 2 2(14) homosynthon. Finally, π-π stacking inter-actions lead to the formation of the three-dimensional structure. The supra-molecular analysis was supported by Hirshfeld surface and two-dimensional fingerprint plot analysis, indicating that the most abundant contacts are associated with H⋯H, O⋯H/H⋯O, N⋯H/H⋯N and C⋯H/H⋯C inter-actions.

Crystal structure and Hirshfeld surface analysis of 8-benzyl-1-[(4-methyl-phen-yl)sulfon-yl]-2,7,8,9-tetra-hydro-1H-3,6:10,13-diep-oxy-1,8-benzodi-aza-cyclo-penta-decine ethanol hemisolvate.

The asymmetric unit of the title compound, 2C31H28N2O4S·C2H6O, contains a parent mol-ecule and a half mol-ecule of ethanol solvent. The main compound stabilizes its mol-ecular conformation by forming a ring with an R 1 2(7) motif with the ethanol solvent mol-ecule. In the crystal, mol-ecules are connected by C-H⋯O and O-H⋯O hydrogen bonds, forming a three-dimensional network. In addition, C-H⋯π inter-actions also strengthen the mol-ecular packing.

In Silico and Chromatographic Methods for Analysis of Biotransformation of Prospective Neuroprotective Pyrrole-Based Hydrazone in Isolated Rat Hepatocytes.

In the current study, chromatographic and in silico techniques were applied to investigate the biotransformation of ethyl 5-(4-bromophenyl)-1-(2-(2-(2-hydroxybenzylidene) hydrazinyl)-2-oxoethyl)-2-methyl-1H-pyrrole-3-carboxylate (11b) in hepatocytic media. The initial chromatographic procedure was based on the employment of the conventional octadecyl stationary phase method for estimation of the chemical stability. Subsequently, a novel and rapid chromatographic approach based on a phenyl-hexyl column was developed, aiming to separate the possible metabolites. Both methods were performed on a Dionex 3000 ThermoScientific (ACM 2, Sofia, Bulgaria) device equipped with a diode array detector set up at 272 and 279 nm for analytes detection. An acetonitrile: phosphate buffer of pH 3.5: methanol (17:30:53 v/v/v) was eluted isocratically as a mobile phase with a 1 mL/min flow rate. A preliminary purification from the biological media was achieved by protein precipitation with methanol. A validation procedure was carried out, where the method was found to correspond to all ICH (Q2) and M10 set criteria. Additionally, an in silico-based approach with the online server BioTransformer 3.0 was applied in an attempt to predict the possible metabolites of the title compound 11b. It was hypothesized that four CYP450 isoforms (1A2, 2C9, 3A4, and 2C8) were involved in the phase I metabolism, resulting in the formation of 12 metabolites. Moreover, docking studies were conducted to evaluate the formation of stable complexes between 11b and the aforementioned isoforms. The obtained data indicated three metabolites as the most probable products, two of which (M9_11b and M10_11b) were synthesized by a classical approach for verification. Finally, liquid chromatography with a mass detector was implemented for comprehensive and summarized analysis, and the obtained results revealed that the metabolism of the 11b proceeds possibly with the formation of glucuronide and glycine conjugate of M11_11b.

Crystal structure of 2,4-di-amino-5-(4-hy-droxy-3-meth-oxy-phen-yl)-8,8-dimethyl-6-oxo-6,7,8,9-tetra-hydro-5H-chromeno[2,3-b]pyridine-3-carbo-nitrile-di-methyl-formamide-water (1/1/1).

In the structure of the title compound, C22H22N4O4·C3H7NO·H2O, the entire tricyclic system is approximately planar except for the carbon atom bearing the two methyl groups; the meth-oxy-phenyl ring is approximately perpendicular to the tricycle. All seven potential hydrogen-bond donors take part in classical hydrogen bonds. The main mol-ecule and the DMF combine to form broad ribbons parallel to the a axis and roughly parallel to the ab plane; the water mol-ecules connect the residues in the third dimension.

Crystal structure and Hirshfeld surface analysis of 4,4'-di-meth-oxy-biphenyl-3,3',5,5'-tetra-carb-oxy-lic acid dihydrate.

In the crystal of the title compound, C18H14O10·2H2O, the arene rings of the biphenyl moiety are tilted at an angle of 24.3 (1)°, while the planes passing through the carboxyl groups are rotated at angles of 8.6 (1) and 7.7 (1)° out of the plane of the benzene ring to which they are attached. The crystal structure is essentially stabilized by O-H⋯O bonds. Here, the carboxyl groups of neighbouring host mol-ecules are connected by cyclic R 2 2(8) synthons, leading to the formation of a three-dimensional network. The water mol-ecules in turn form helical supra-molecular strands running in the direction of the crystallographic c-axis (chain-like water clusters). The second H atom of each water mol-ecule provides a link to a meth-oxy O atom of the host mol-ecule. A Hirshfeld surface analysis was performed to qu-antify the contributions of the different inter-molecular inter-actions, indicating that the most important contributions to the crystal packing are from H⋯O/O⋯H (37.0%), H⋯H (26.3%), H⋯C/C⋯H (18.5%) and C⋯O/O⋯C (9.5%) inter-actions.

Synthesis, solvent role, absorption and emission studies of cytosine derivative

The (E)-4-((4-hydroxy-3-methoxy-5-nitrobenzylidene) amino) pyrimidin-2(1H)-one (C5NV) was synthesized from cytosine and 5-nitrovanilline by simple straightforward condensation reaction. The structural characteristics of the compound was determined and optimized by WB97XD/cc-pVDZ basis set. The vibrational frequencies were computed and subsequently compared to the experimental frequencies. We investiated the electronic properties of the synthesized compound in gas and solvent phases using the time-dependent density functional theory (TD-DFT) approach, and compared them to experimental values. The fluorescence study showed three different wavelengths indicating the nature of the optical material properties. Frontier molecular orbital (FMO) and molecular electrostatic potential (MEP) analyses were conducted for the title compound, and electron localized functions (ELF) and localized orbital locators (LOL) were used to identify the orbital positions of localized and delocalized atoms. Non-covalent interactions (H-bond interactions) were investigated using reduced density gradients (RDGs). The objective of the study was to determine the physical, chemical, and biological properties of the C5NV. The molecular docking study was conducted between C5NV and 2XNF protein, its lowest binding energy score is −7.92 kcal/mol.

Spectroscopic characterizations, RDG and docking study of 2-[3-(4-chlorophenyl)-5-(4-(propane-2-yl) phenyl)-4,5-dihydro-1H pyrozol-1-yl]-4-(4-fluorophenyl)-1,3-thiazole

Abstract The theoretical calculations for 2-[3-(4-chlorophenyl)-5-(4-(propane-2-yl) phenyl)-4,5-dihydro-1H-pyrazol-1-yl]-4-(4-fluorophenyl)-1,3-thiazole (CPDFT) are performed using the Density Functional Theory (DFT) technique employing the B3LYP/cc-pVDZ and LanL2MB basis sets. Theoretical infrared (IR) and Raman frequencies as well as structural investigation were performed. The molecular structure demonstrating the presence of charge transfer and determining the bond length, bond angle of the header molecule. FMO deals about the both occupied and unoccupied orbitals of the molecule are computed. A molecular electrostatic potential map was created and analysed to identify the sites of electrophilic and nucleophilic areas of CPDFT. The ligand-protein interaction of the title compound was assessed by docking studies, indicating a strong affinity between the title compound and the target macromolecules. A reduced density gradient graph, electron localization electron and Localized orbital locator was employed to discern the non-covalent interactions of CPDFT.

Pyridazine derivative as potent antihyperglycemic agent: Synthesis, crystal structure, α-amylase and α-glucosidase inhibition and computational studies

In this study, a pyridazine derivative (PDZ-1) was synthesized and characterized by using 13C NMR, 1H NMR, FT-IR, UV–Vis, HRMS-ESI and single-crystal X-ray diffraction analysis (XRD). Density functional theory methods at the B3LYP/6–311++G** level of theory predict very good correlations in the geometrical parameters and spectra when they are compared with the corresponding experimental ones. The presence of dimer explains the broad IR band due to CH···O interactions. The scaled force constants and the 75 vibration modes of PDZ-1 have been completely assigned using the scaled quantum mechanical force field (SQMFF) methodology. The deactivating character of Cl atom probably explains that the densities of pyridazine rings in both media are higher than that corresponding to chlorobenzyl, as revealed by AIM study while NBO calculations show that the derivative is most stable in gas phase than ethanol solution. Frontier orbital studies reveal that PDZ-1 is most reactive in ethanol than in the gas phase. The title compound showed a potent α-glucosidase and α-amylase inhibition compared to Acarbose (IC50 = 113.6 ± 1.17 µM, 124.5 ± 0.64 µM, respectively) with IC50 values of 17.32 ± 0.76 and 109.41± 0.87 µM, respectively. In addition, molecular docking studies were performed to determine the binding modes and energies between PDZ-1 and the target enzymes.

5‐Bromosalicylaldehyde: Theoretical, Experimental and Spectroscopic (FT‐IR, Raman, H1 and C13‐NMR, UV‐Vis) Studies and Their Photovoltaic Parameters

AbstractThis study aims to identify a 5‐bromosalicylaldehyde (5BSA) and assess its performance for application in organic solar cells. In the current work, the 5BSA was investigated using various techniques such as FT‐IR, Raman, NMR, and UV‐Vis spectroscopy to characterize the title molecule. The possible conformers of the 5BSA were studied using the MMFF methodology in Spartan software. The geometry optimization of modifications for each conformation was computed using the DFT approach for the B3LYP/6‐311++G(d,p) functional. The energy and dipole moment of most stable form were determined −1879057.42 kcal/mol and 1.455 Debye, respectively. The FT‐IR and Raman vibrational frequencies, the H1 and C13 NMR chemical shift values (in vacuum and in DMSO‐d6), the UV spectrum calculations (both in vacuum and in the solvent ethanol), the HOMO‐LUMO energy, and the map of MEP. Meanwhile, by considering the properties of organic photovoltaic cells, the open‐circuit voltage (VOC), hole reorganization energy (λh) and electron reorganization energy (λe), light‐harvesting efficiency (LHE), total reorganization energy (λtotal), the short‐circuit current density (Jsc), the driving force (ΔGinject), binding energy (Eb) were also computed for the title compound. In addition, transition density matrix (TDM) and density of states (DOS) analyses were conducted for the 5BSA molecule.

Synthesis, crystal structure and Hirshfeld surface analysis of 2-phenyl-3-(prop-2-yn-1-yl-oxy)quin-oxaline.

In the title compound, C17H12N2O, the quinoxaline moiety shows deviations of 0.0288 (7) to -0.0370 (7) Å from the mean plane (r.m.s. deviation of fitted atoms = 0.0223 Å). In the crystal, corrugated layers two mol-ecules thick are formed by C-H⋯N hydrogen bonds and π-stacking inter-actions.

Crystal structure and Hirshfeld surface analysis of 6-imino-8-(4-methyl-phen-yl)-1,3,4,6-tetra-hydro-2H-pyrido[1,2-a]pyrimidine-7,9-dicarbo-nitrile.

In the ten-membered 1,3,4,6-tetra-hydro-2H-pyrido[1,2-a]pyrimidine ring system of the title compound, C17H15N5, the 1,2-di-hydro-pyridine ring is essentially planar (r.m.s. deviation = 0.001 Å), while the 1,3-diazinane ring has a distorted twist-boat conformation. In the crystal, mol-ecules are linked by N-H⋯N and C-H⋯N hydrogen bonds, forming a three-dimensional network. In addition, C-H⋯π inter-actions form layers parallel to the (100) plane. Thus, crystal-structure cohesion is ensured. According to a Hirshfeld surface study, H⋯H (40.4%), N⋯H/H⋯N (28.6%) and C⋯H/H⋯C (24.1%) inter-actions are the most important contributors to the crystal packing.

Poly[(μ-2,3-diethyl-7,8-di-methyl-quinoxaline-κ2N:N)(2,3-diethyl-7,8-di-methyl-quinoxaline-κN)-μ-nitrato-κ2O:O'-nitrato-κ2O,O'-disilver(I)].

The structure of the title compound, [C14H18N2)2Ag2](NO3)2, contains subtle differences in ligand, metal, and counter-anion coordination. One quinoxaline ligand uses one of its quinoxaline N atoms to bond to one silver cation. That silver cation is bound to a second quinoxaline which, in turn, is bound to a second silver atom; thereby using both of its quinoxaline N atoms. A nitrate group bonds with one of its O atoms to the first silver and uses the same oxygen to bond to a silver atom (related by symmetry to the second), thereby forming an extended network. The second nitrate group on the other silver bonds via two nitrate O atoms; one silver cation therefore has a coordination number of three whereas the second has a coordination number of four. One of the quinoxaline ligands has a disordered ethyl group.

Structural Characterization of 4-(4-Nitrophenyl)thiomorpholine, a Precursor in Medicinal Chemistry

4-(4-nitrophenyl)thiomorpholine, the title compound, has been used as a precursor for the corresponding 4-thiomorpholinoaniline, which is a useful building block in medicinal chemistry. The crystal and molecular structures of the title compound, however, have not been described thus far. We synthesized the title compound by means of a nucleophilic aromatic substitution reaction of 4-fluoronitrobenzene and thiomorpholine and structurally characterized it by X-ray crystallography, DFT calculations, and Hirshfeld surface analysis. In the crystal, the molecule exhibits an approximately CS-symmetric structure, with the nitrogen-bound 4-nitrophenyl group in a quasi axial position on the six-membered thiomorpholine ring in a low-energy chair conformation. The solid-state structure of the title compound is markedly different from that of its morpholine analogue. This can be ascribed to the formation of centrosymmetric dimers through intermolecular C–H···O weak hydrogen bonds involving the methylene groups adjacent to the sulfur atom and face-to-face aromatic stacking.

Trans-Di-bromido-tetra-kis-(5-methyl-1H-pyrazole-κN2)manganese(II).

The title compound, trans-di-bromido-tetra-kis-(5-methyl-1H-pyrazole-κN 2)manganese(II), [MnBr2(C4H6N2)4] or [Mn(3-MePzH)4Br2] (1) crystallizes in the triclinic P space group with the cell parameters a = 7.6288 (3), b = 8.7530 (4), c = 9.3794 (4) Å and α = 90.707 (4), β = 106.138 (4), γ = 114.285 (5)°, V = 542.62 (5) Å3, T = 120 K. The asymmetric unit contains only half the mol-ecule with the manganese atom is situated on a crystallographic inversion center. The 3-MePzH ligands are present in an AABB type manner with two methyl groups pointing up and the other two down. The supra-molecular architecture is characterized by several inter-molecular C-H⋯N, N-H⋯Br, and C-H⋯π inter-actions. Earlier, a polymorphic structure of [Mn(3-MePzH)4Br2] (2) with a similar geometry and also an AABB arrangement for the pyrazole ligands was described [Reedijk et al. (1971 ▸). Inorg. Chem. 10, 2594-2599; a = 8.802 (6), b = 9.695 (5), c = 7.613 (8) Å and α = 105.12 (4), β = 114.98 (4), γ = 92.90 (3)°, V = 558.826 (5) Å3, T = 295 K]. A varying supra-molecular pattern was reported, with the structure of 1 featuring a herringbone type pattern while that of structure 2 shows a pillared network type of arrangement along the a axis. A nickel complex [Ni(3-MePzH)4Br2] isomorphic to 1 and the analogous chloro derivatives of FeII, CoII and CuII are also known.

4-Fluoro-benzyl (Z)-2-(2-oxoindolin-3-yl-idene)hydrazine-1-carbodi-thio-ate.

The title compound, C16H12FN3OS, a fluorinated di-thio-carbazate imine derivative, was synthesized by the one-pot, multi-component condensation reaction of hydrazine hydrate, carbon di-sulfide, 4-fluoro-benzyl chloride and isatin. The compound demonstrates near-planarity across much of the mol-ecule in the solid state and a Z configuration for the azomethine C=N bond. The Z form is further stabilized by the presence of an intra-molecular N-H⋯O hydrogen bond. In the extended structure, mol-ecules are linked into dimers by N-H⋯O hydrogen bonds and further connected into chains along either [20] or [100] by weak C-H⋯S and C-H⋯F hydrogen bonds, which further link into corrugated sheets and in combination form the overall three-dimensional network.

Supramolecular complex catalyzed green synthesis of 9-(2-Ethylhexyl) carbazole: Structural, optical and DFT investigations

Green chemical principles such as (a) bio-renewable solvent utilization, (b) phase transfer catalysis (c) coloumn chromatography free methodologies, and (d) mild reaction conditions (i.e., room temperature, open atmosphere enough to carry out alkylation of carbazole) were optimized during the synthesis of 9-(2-Ethylhexyl) carbazole. High yield of title compound (96 %) was achieved with 1.0 equivalents of base NaOH and catalytic amount (0.1 equivalents) of 18C6 using a combination of 2-MeTHF and water green solvents. Structure of the Carbazole, 9-(2-Ethylhexyl)carbazole was conformed by analyzing the spectral data such as NMR, IR and Mass. DFT studies were explored to analyze various energy components and reactivity descriptors of the title product. The energy gap in between HOMO and LUMO of the this compound is found to be -4.59ev. Further, UV–Visible spectral analysis has been carried out in various solvents in different molarities to understand the stability of the compound with respect to various wavelength points. The increment of dielectric constant of the solvent (from 1,4 Dioxane to Acetonitrile in upward direction) also indicates major blue side shift. These studies are expected to offer critical insight into the correlation between structural, optical parameters.

Synthesis, structural examination, molecular interaction analysis, invitro and insilico anticancer activity investigation of a new curcumin derivative: 1- (4 – chlorobenzoyl) - 3, 5 - bis ((E) - 4 - methoxybenzylidene) piperidin - 4 – one

The title material, C28H24ClNO4, was synthesized using the Claisen-Schmidt condensation reaction and Schotten-Baumann reaction methods and crystallized. Geometrical parameters were determined for the grown crystal using the Single Crystal X-Ray Diffraction (SCXRD) technique. The title compound has been characterized and anzalyzed for its optical properties via1H1 and 13C NMR, FT-Raman, and FT-IR, UV and PL spectra. The melting point and thermal stability have been investigated using TG/DTA thermograms.Hirshfeld surfaces were developed in order to observe and quantify short contacts, CH…π and π...π stacking interactions. To determine how various interactions influence the overall Hirshfeld surface, 2D fingerprint plots were created, and it was discovered that the H…H contact's contribution was the most significant. Cytotoxic effect on HEK293 cell lines was performed and found to be highly toxic. To determine the compound's efficacy as an anticancer agent, a research was conducted using MCF-7 cell lines. Molecular docking simulation revealed that the title material (ligand) fits well at the active site of the target protein with PDB ID: 1M17. Pharmacokinetic, and ADMET properties revealed that the compound is exceedingly orally active, and after further biological and pharmaceutical investigations, the compound can be recommended as a drug candidate.

Synthesis, crystal structure, DFT, vibrational properties, Hirshfeld surface and antitumor activity studies of a new compound 2-(2-chloro-6-(m-tolyl)imidazo[1,2-a]pyridin-3-yl)-N,N-diethylacetamide

Imidazo[1,2-a]pyridine derivatives are a kind of fused heterocyclic substances, which play an important role in the chemical field and have been proved to be the core fragments of various drug molecules. In this study, a new title compound was finally synthesized by cyclization, substitution, Suzuki coupling, hydrolysis and condensation. And the crystal of the title compound was obtained by single crystal culture. The structure of 2-(2-chloro-6-(m-tolyl)imidazo[1,2-a]pyridin-3-yl)-N,N-diethylacetamide was confirmed by 1H NMR, 13C NMR, FT-IR and single crystal X-ray diffraction. In addition, the title compound was theoretically calculated at the level of 6–311+G (2d, p) based on density functional method B3LYP, and the molecular structure optimized by DFT was consistent with the results obtained by X-ray diffraction. By calculating the Hirschfield surfaces and 2D fingerprints of molecules, the interactions between molecules can be visually revealed based on the size and color of the spots near the atoms. In addition, according to the characteristic vibration absorption band, the vibration of the title compound is reliably attributed. Furthermore, MEP, RDG, and ELF analyses were conducted to characterize the reaction sites susceptible to electrophilic and nucleophilic attacks. FMOs was used to evaluate the stability of the molecular structure. Finally, the results of the determination of biological activity showed that the compound exhibited significant inhibitory activity against HCT116 cancer cell.

5-(9-(p-Tolyl)-2,3,4,4a,9,9a-hexahydro-1H-1,4-methanocarbazol-6-yl)thiophene-2-carbaldehyde

Donor–π spacer–acceptor (D–π–A) dyes are among the most attractive structures for the design of organic dye-sensitized solar cells (DSSCs). Typically, the key intermediates for these sensitizers are D–π compounds containing an aldehyde group to which an anchor acceptor group is attached via the Knoevenagel reaction. In this communication, 5-(9-(p-tolyl)-2,3,4,4a,9,9a-hexahydro-1H-1,4-methanocarbazol-6-yl)thiophene-2-carbaldehyde was prepared via the Suzuki cross-coupling reaction. The structure of the newly synthesized compound was established by means of high-resolution mass spectrometry, 1H NMR, 13C NMR, IR, and UV–Vis spectroscopy. The title compound would be used in the synthesis of sensitizers for DSSCs.