New2-((2-(2,4-dinitrophenyl)hydrazineeylidene) derivatives: design, synthesis, in silico, and in vitro anticancer studies.

A series of novel hydrazone compounds have been synthesized by the condensation of hydrazines and different substituted salicylaldehydes at a molar ratio of 1:1 in one step reaction and characterized by FT-IR, ESI-MS, 1H NMR, and single crystal x-ray diffraction. The crystal structure of the compound shows a trans configuration around the C = N bond and triclinic system with P -1/-p 1. Synthesized compounds were screened for cytotoxicity activities against A375 (melanoma), HT-29 (Colon), and A549 (lung) cancer cell lines. Among them, compound 2 exhibited the highest cytotoxic effect against the A375 cell line (IC50 = 0.30 µM) and HT-29 cell line (1.68 µM), compared to those of apatinib as a reference standard drug (0.28, 1.49 µM, respectively). The cytocompatibility assay on the L929 normal cell line and the hemolysis assay on human RBC were used to validate the non-toxic action. From DFT calculation, the various parameters such as HOMO-LUMO energies, Hirshfeld, and MEP have been studied. Furthermore, in silico molecular docking with three receptors was studied. Among four compounds, compound 2 has the lowest binding energy against cyclin dependent kinase (ΔGb = -9.3 kcal/mol). In addition to this, molecular dynamics (MD) simulation was also performed. Based on this study, these novel hydrazones can be considered a promising anticancer agent due to their potent cytotoxicity activities and computational analysis.Communicated by Ramaswamy H. Sarma.

A comprehensive study on the photophysical and non-linear optical properties of thienyl-chalcone derivatives.

The impact of the substitutional position of the chorine atom on the non-linear optical (NLO) response of chalcone derivatives is reported in this paper. Two thienyl-chalcone derivatives, (E)-3-(2,4-dichloro-phenyl)-1-(2,5-dichlorothiophen-3-yl)prop-2-en-1-one (3A25D2) and (E)-3-(2,6-dichloro-phenyl)-1-(2,5-dichlorothiophen-3-yl)prop-2-en-1-one (3A25D4), are synthesized, and their crystal structures were determined by single-crystal X-ray diffraction analysis. The photophysical and third-order NLO properties of 3A25D2 and 3A25D4 were investigated experimentally and computationally. The third-order NLO properties of 3A25D2 and 3A25D4 dissolved in N,N-dimethylformamide (DMF) were studied using Z-scan technique with 800 nm, 70 femtosecond (fs) pulses, and 532 nm continuous wave (CW) laser excitation. Closed aperture data recorded with fs pulses revealed positive non-linearity of both the compounds, while a strong negative non-linearity was observed in the CW regime. Open aperture data revealed that both the compounds exhibit positive non-linear absorption in fs pulsed and CW domains. Several wave function analysis methods, such as the inter-fragment charge transfer (IFCT) analysis, hole-electron analysis, (hyper)polarizability density analysis, and decomposition of the (hyper)polarizability contribution by numerical integration, were carried out to study the optical properties and charge transfer mechanism. In addition, the influence of the medium (liquid and crystalline) and external field wavelength on the optical properties of the two molecules were analyzed. Thermal and electronic contributions toward NLO properties were studied experimentally. The theoretically calculated cubic hyperpolarizability γ(-ω; ω, ω, -ω) in liquid for 3A25D2 and 3A25D4 were 4.69 × 10-34 and 2.68 × 10-34 esu, whereas the corresponding femtosecond regime Z-scan results gave 4.35 × 10-34 and 3.78 × 10-34 esu, respectively.

Green synthesis of selenium based N-heterocyclic carbene compounds; structural, in-vitro anticancer and molecular docking studies.

Benzimidazolium salts (3-6) were synthesized as stable N-Heterocyclic Carbene (NHC) precursors and their selenium-NHC compounds/Selenones (7-10) were prepared using water as a solvent. Characterization of each of the synthesized compounds was carried out by various analytical and spectroscopic (FT-IR, 1H-, 13C NMR) methods. X-ray crystallographic analyses of single crystals obtained for salts 3 and 5 were carried out. Synthesized salts and their Se-NHCs were tested in-vitro for their anticancer potential against Cervical Cancer Cell line from Henrietta Lacks (HeLa), Breast cancer cell line (MDA-MB-231), Adenocarcinoma cell line (A549) and human normal endothelial cell line (EA.hy926). MTT assay was used for analysis and compared with standard drug 5-flourouracil. Benzimidazolium salts (3-6) and their selenium counter parts (7-10) were found potent anticancer agents. Salt 3-5 were found to be potent anticancer against HeLa with IC50 values 0.072, 0.017 and 0.241 µM, respectively, which are less than standard drug (4.9 µM). The Se-NHCs (7-10) had also shown significant anticancer potential against HeLa with IC50 values less than standard drug. Salts 3, 4 against EA.hy926, compounds 3,5,6, and 10 against MDA-MB-321, and compounds 4, 10 against A-549 cell line were found more potent anticancer agents with IC50 values less than standard drug. Molecular docking for (7-10) showed their good anti-angiogenic potential having low binding energy and significant inhibition constant values with VEGFA (vascular endothelial growth factor), EGF (human epidermal growth factor), COX1 (cyclooxygenase-1) and HIF (hypoxia inducible factor).

Ultrafast Nonlinear Optical and Structure-Property Relationship Studies of Pyridine-Based Anthracene Chalcones Using Z-Scan, Degenerate Four-Wave Mixing, and Computational Approaches.

The structural, thermal, linear, and femtosecond third-order nonlinear optical (NLO) properties of two pyridine-based anthracene chalcones, (2E)-1-(anthracen-9-yl)-3-(pyridin-2-yl)prop-2-en-1-one (2PANC) and (2E)-1-(anthracen-9-yl)-3-(pyridin-3-yl)prop-2-en-1-one (3PANC), were investigated. These two chalcones were synthesized following the Claisen-Schmidt condensation method. Optically transparent single crystals were achieved using a slow evaporation solution growth technique. The presence of functional groups in these molecules was established by Fourier transform infrared and NMR spectroscopic data. The detailed solid-state structure of both chalcones was determined from the single-crystal X-ray diffraction data. Both crystals crystallized in the centrosymmetric triclinic space group P1̅ with the nuance of unit cell parameters. The crystals (labeled as 2PANC and 3PANC) have been found to be transparent optically [in the entire visible spectral region] and were found to be thermally stable up to 169 and 194 °C, respectively. The intermolecular interactions were investigated using the Hirshfeld surface analysis, and the band structures (highest occupied molecular orbital-lowest unoccupied molecular orbital, excited-state energies, global chemical reactivity descriptors, and molecular electrostatic potentials) were studied using density functional theory (DFT) techniques. The ultrafast third-order NLO properties were investigated using (a) Z-scan and (b) degenerate four-wave mixing (DFWM) techniques using ∼50 fs pulses at 800 nm (1 kHz, ∼4 mJ) from a Ti:sapphire laser amplifier. Two-photon-assisted reverse saturable absorption, self-focusing nonlinear refraction, optical limiting, and optical switching behaviors were witnessed from the Z-scan data. 3PANC demonstrated a stronger two-photon absorption coefficient, while 2PANC depicted a stronger nonlinear refractive index among the two. The time-resolved DFWM data demonstrated that the decay times of 2PANC and 3PANC were ∼162 and ∼180 fs, respectively. The second hyperpolarizability (γ) values determined by DFT, Z-scan, and DFWM were found to be in good correlation (with a magnitude of ∼10-34 esu). The ultrafast third-order NLO response, significant NLO properties, and thermal stability of these chalcones brands them as potential candidates for optical power limiting and switching applications.

New 3-O-substituted xanthone derivatives as promising acetylcholinesterase inhibitors.

A new series of 3-O-substituted xanthone derivatives were synthesised and evaluated for their anti-cholinergic activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The results indicated that the xanthone derivatives possessed good AChE inhibitory activity with eleven of them (5, 8, 11, 17, 19, 21-23, 26-28) exhibited significant effects with the IC50 values ranged 0.88 to 1.28 µM. The AChE enzyme kinetic study of 3-(4-phenylbutoxy)-9H-xanthen-9-one (23) and ethyl 2-((9-oxo-9H-xanthen-3-yl)oxy)acetate (28) showed a mixed inhibition mechanism. Molecular docking study showed that 23 binds to the active site of AChE and interacts via extensive π-π stacking with the indole and phenol side chains of Trp86 and Tyr337, besides the hydrogen bonding with the hydration site and π-π interaction with the phenol side chain of Y72. This study revealed that 3-O-alkoxyl substituted xanthone derivatives are potential lead structures, especially 23 and 28 which can be further developed into potent AChE inhibitors.

Crystal structure of (E)-N'-(3,4-di-hydroxy-benzyl-idene)-4-hy-droxy-benzohydrazide.

In the title benzohydrazide derivative, C14H12N2O4, the azomethine C=N double bond has an E configuration. The hydrazide connecting bridge, (C=O)-(NH)-N=(CH), is nearly planar with C-C-N-N and C-N-N=C torsion angles of -177.33 (10) and -174.98 (12)°, respectively. The 4-hy-droxy-phenyl and 3,4-di-hydroxy-phenyl rings are slightly twisted, making a dihedral angle of 9.18 (6)°. In the crystal, mol-ecules are connected by N-H⋯O and O-H⋯O hydrogen bonds into a three-dimensional network, while further consolidated via π-π inter-actions [centroid-centroid distances = 3.6480 (8) and 3.7607 (8) Å]. The conformation is compared to those of related benzyl-idene-4-hy-droxy-benzohydrazide derivatives.

Crystal structure of a second monoclinic polymorph of 3-meth-oxy-benzoic acid with Z' = 1.

A new polymorphic form of the title compound, C8H8O3, is described in the centrosymmetric monoclinic space group P21/c with Z' = 1 as compared to the first polymorph, which crystallizes with two conformers (Z' = 2) in the asymmetric unit in the same space group. In the crystal of the second polymorph, inversion dimers linked by O-H⋯O hydrogen bonds occur and these are linked into zigzag chains, propagating along the b-axis direction by C-H⋯O links. The crystal structure also features a weak π-π inter-action, with a centroid-to-centroid distance of 3.8018 (6) Å. The second polymorph of the title compound is less stable than the reported first polymorph, as indicated by its smaller calculated lattice energy.

Conformational dimorphism of 2,2'-methyl-enebis(isoindoline-1,3-dione).

In this study, a new monoclinic polymorph (space group C2/c) of 2,2'-methyl-enebis(isoindoline-1,3-dione), C17H10N2O4, is reported and compared to the previously reported triclinic polymorph (space group P ). Similarly, both polymorphs consist of a unique mol-ecule in the asymmetric unit (Z' = 1). The mol-ecular conformations of the two polymorphs are very similar, as shown by the r.m.s. deviation of 0.368 Š(excluding all H atoms). The inter-molecular inter-actions of both polymorphs are described along with the Hirshfeld surface analysis, and the lattice energies are calculated.

Crystal structure and Hirshfeld surface analysis of a chalcone derivative: (E)-3-(4-fluoro-phen-yl)-1-(4-nitro-phen-yl)prop-2-en-1-one.

The mol-ecular structure of the title chalcone derivative, C15H10FNO3, is nearly planar and the mol-ecule adopts a trans configuration with respect to the C=C double bond. The nitro group is nearly coplanar with the attached benzene ring, which is nearly parallel to the second benzene ring. In the crystal, mol-ecules are connected by pairs of weak inter-molecular C-H⋯O hydrogen bonds into inversion dimers. The dimers are further linked by another C-H⋯O hydrogen bond and a C-H⋯F hydrogen bond into sheets parallel to (104). π-π inter-actions occur between the sheets, with a centroid-centroid distance of 3.8860 (11) Å. Hirshfeld surface analysis was used to investigate and qu-antify the inter-molecular inter-actions.

Crystal Correlation Of Heterocyclic Imidazo[1,2-a]pyridine Analogues and Their Anticholinesterase Potential Evaluation.

Imidazo[1,2-a]pyridine-based compounds are clinically important to the treatments of heart and circulatory failures, while many are under development for pharmaceutical uses. In this study, a series of imidazo[1,2-a]pyridine-based derivatives 2(a-o) were synthesized by reacting a-haloketones with 2-aminopyridines in a basic media at ambient temperature. Single crystal X-ray diffraction studies suggest that with low degree-of-freedom, the introduction of bulky adamantyl or electron-rich biphenyl moiety into the imidazopyridine derivatives will not affect its structural occupancy. Imidazo[1,2-a]pyridine-based derivatives with biphenyl side chain are potential AChE inhibitors. Compound 2h which bears a biphenyl side chain and methyl substituent at the position R4 of the imidazo[1,2-a]pyridine ring showed the strongest AChE inhibition with an IC50 value of 79 µM. However, imidazo[1,2-a]pyridine derivatives with phenyl side chain exhibit better BChE inhibition effect among the series. Compound 2j with 3,4-dichlorophenyl side chain and unsubstituted imidazo[1,2-a]pyridine ring appears to be the strongest BChE inhibitor with an IC50 value of 65 µM and good selectivity. The inhibitory effects of active compounds were further confirmed by computational molecular docking studies. The results unveiled that peripheral anionic sites of AChE and acyl pocket of BChE were the predominated binding sites for the subjected inhibitors.

Crystal structure and Hirshfeld surface analysis of (E)-3-(2-chloro-phen-yl)-1-(2,5-di-chloro-thio-phen-3-yl)prop-2-en-1-one.

The mol-ecular structure of the title compound, C13H7Cl3OS, consists of a 2,5- di-chloro-thio-phene ring and a 2-chloro-phenyl ring linked via a prop-2-en-1-one spacer. The dihedral angle between the 2,5-di-chloro-thio-phene and 2-chloro-phenyl rings is 9.69 (12)°. The mol-ecule has an E configuration about the C=C bond and the carbonyl group is syn with respect to the C=C bond. The mol-ecular conformation is stabilized by two intra-molecular C-H⋯Cl contacts and one intra-molecular C-H⋯O contact, forming S(5)S(5)S(6) ring motifs. In the crystal, the mol-ecules are linked along the a-axis direction through van der Waals forces and along the b axis by face-to-face π-stacking between the thio-phene rings and between the benzene rings of neighbouring mol-ecules, forming corrugated sheets lying parallel to the bc plane. The inter-molecular inter-actions in the crystal packing were further analysed using Hirshfield surface analysis, which indicates that the most significant contacts are Cl⋯H/ H⋯Cl (28.6%), followed by C⋯H/H⋯C (11.9%), C⋯C (11.1%), H⋯H (11.0%), Cl⋯Cl (8.1%), O⋯H/H⋯O (8.0%) and S⋯H/H⋯S (6.6%).

Crystal structure and Hirshfeld surface analysis of a bromo-chalcone: (E)-1-(3-bromo-phen-yl)-3-(2,6-di-chloro-phen-yl)prop-2-en-1-one.

In the title chalcone derivative, C15H9BrCl2O, the aryl rings are inclined to each by 14.49 (17)°, and the configuration about the C=C bond is E. There is a short intra-molecular C-H⋯Cl contact present resulting in the formation of an S(6) ring motif. In the crystal, the shortest inter-molecular contacts are Cl⋯O contacts [3.173 (3) Å] that link the mol-ecules to form a 21 helix propagating along the b-axis direction. The helices stack up the short crystallographic a axis, and are linked by offset π-π inter-actions [inter-centroid distance = 3.983 (1) Å], forming layers lying parallel to the ab plane. A qu-anti-fication of the inter-molecular contacts in the crystal were estimated using Hirshfeld surface analysis and two-dimensional fingerprint plots.

Crystal structure and Hirshfeld surface analysis of (2E)-3-(2,4-di-chloro-phen-yl)-1-(2,5-di-chloro-thio-phen-3-yl)prop-2-en-1-one.

The mol-ecular structure of the title compound, C13H6Cl4OS, consists of a 2,5-di-chloro-thio-phene ring and a 2,4-di-chloro-phenyl ring linked via a prop-2-en-1-one spacer. The dihedral angle between the 2,5-di-chloro-thio-phene ring and the 2,4-di-chloro-phenyl ring is 12.24 (15)°. The mol-ecule has an E configuration about the C=C bond and the carbonyl group is syn with respect to the C=C bond. The mol-ecular conformation is stabilized by intra-molecular C-H⋯Cl contacts, producing S(6) and S(5) ring motifs. In the crystal, the mol-ecules are linked along the a-axis direction through face-to-face π-stacking between the thio-phene rings and the benzene rings of the mol-ecules in zigzag sheets lying parallel to the bc plane along the c axis. The inter-molecular inter-actions in the crystal packing were further analysed using Hirshfield surface analysis, which indicates that the most significant contacts are Cl⋯H/ H⋯Cl (20.8%), followed by Cl⋯Cl (18.7%), C⋯C (11.9%), Cl⋯S/S⋯Cl (10.9%), H⋯H (10.1%), C⋯H/H⋯C (9.3%) and O⋯H/H⋯O (7.6%).

Crystal structure and Hirshfeld surface analysis of (2E)-3-(3-bromo-4-fluoro-phen-yl)-1-(3,4-di-meth-oxy-phen-yl)prop-2-en-1-one.

In the mol-ecule of the title compound, C17H14BrFO3, the aromatic rings are tilted with respect to the enone bridge by 13.63 (14) and 4.27 (15)°, and form a dihedral angle 17.91 (17)°. In the crystal, centrosymmetrically related mol-ecules are linked by pairs of C-H⋯O hydrogen bonds into dimeric units, forming rings of R22(14) graph-set motif. The dimers are further connected by weak C-H⋯O hydrogen inter-actions, forming layers parallel to (10). Hirshfeld surface analysis shows that van der Waals inter-actions constitute the major contribution to the inter-molecular inter-actions, with H⋯H contacts accounting for 29.7% of the surface.

Crystal structure and Hirshfeld surface analysis of (E)-3-(2-chloro-4-fluoro-phen-yl)-1-(2,5-di-chloro-thio-phen-3-yl)prop-2-en-1-one.

In the title chalcone-thio-phene derivative, C13H6Cl3FOS, the aromatic rings are inclined to one another by 12.9 (2)°, and the thio-phene ring is affected by π-conjugation. In the crystal, mol-ecules are linked by C-H⋯F hydrogen bonds, forming an R22(8) ring motif. A Hirshfeld surface analysis was conducted to verify the contribution of the different inter-molecular inter-actions. The shape-index surface clearly shows that the two sides of the mol-ecules are involved in the same contacts with neighbouring mol-ecules and the curvedness plots show flat surface patches characteristic of planar stacking.

Sensing study of quinoxaline analogues with theoretical calculation, single-crystal X-ray structure and real application in commercial fruit juices.

Single-crystal X-ray structures of dimeric quinoxaline aldehyde (QA), quinoxaline dihydrazone (DHQ) and HQNM (Goswami S et al. 2013 Tetrahedron Lett.54, 5075-5077. (doi:10.1016/j.tetlet.2013.07.051); Goswami S et al. 2014 RSC Adv.4, 20 922-20 926. (doi:10.1039/C4RA00594E); Goswami S et al. 2014 New J. Chem.38, 6230-6235. (doi:10.1039/C4NJ01498G)) are reported along with the theoretical study. Among them, QA is not acting as an active probe, but DHQ and HQNM are serving as selective and sensitive probe for the Fe3+ cation and the Ni2+ cation, respectively. DHQ can also detect the Fe3+ in commercial fruit juices (grape and pomegranate).

Crystal structure and Hirshfeld surface analysis of (2E)-3-(3-chloro-phen-yl)-1-(3,4-di-meth-oxy-phen-yl)prop-2-en-1-one.

In title compound, C17H15ClO3, the dihedral angle between the benzene and chloro-phenyl rings is 18.46 (7)°. In the crystal, mol-ecules are linked by C-H⋯O hydrogen contacts, enclosing an R22(14) ring motif, and by a further C-H⋯O hydrogen contact, forming a two-dimensional supra-molecular structure extending along the direction parallel to the ac plane. Hirshfeld surface analysis shows that van der Waals inter-actions constitute the major contribution to the inter-molecular inter-actions, with H⋯H contacts accounting for 36.2% of the surface.

Crystal structure and Hirshfeld surface analysis of a pyridiniminium bromide salt: 1-[2-(adamantan-1-yl)-2-oxoeth-yl]pyridin-4-iminium bromide.

In the cation of the title salt, C17H23N2O+·Br-, the adamantyl moiety and the pyridiniminium ring are inclined to the ketone bridge by torsion angles of -78.1 (2) (C-C-C=O) and 58.3 (2)° (C-C-N-C), respectively, and the ketone bridge has a C-C-C-N torsion angle of 174.80 (15)°. In the crystal, the cations are connected into chains parallel to the c axis by C-H⋯O hydrogen bonds. The chains are further linked into layers parallel to the bc plane by N-H⋯Br and C-H⋯Br hydrogen bonds, C-H⋯π inter-actions and π-π stacking inter-actions [centroid-to-centroid distance = 3.5657 (11) Å]. A Hirshfeld surface analysis, which comprises the dnorm surface, electrostatic potential map and two-dimensional fingerprint plots, was carried out to verify the contribution of the various inter-molecular inter-actions.

Synthesis, spectroscopic and Hirshfeld surface analysis and fluorescence studies of (2E,2'E)-3,3'-(1,4-phenyl-ene)bis-[1-(4-hy-droxy-phen-yl)prop-2-en-1-one] N,N-di-methyl-formamide disolvate.

In the bis-chalcone mol-ecule of the title compound, C24H18O4·2C3H7NO, the central benzene and terminal hy-droxy-phenyl rings form a dihedral angle of 14.28 (11)° and the central C=C double bond adopts a trans configuration. In the crystal, the bis-chalcone and solvate mol-ecules are inter-connected via O-H⋯O hydrogen bonds, which were investigated by Hirshfeld surface analysis. Solid-state fluorescence was measured at λex = 4400 Å. The emission wavelength appeared at 5510 Å, which corresponds to yellow light and the solid-state fluorescence quantum yield (Ff) is 0.18.

Crystal structure and Hirshfeld surface analysis of a pyridiniminium bromide salt: 1-[2-([1,1'-biphen-yl]-4-yl)-2-oxoeth-yl]-3-methyl-1,4-di-hydro-pyridin-4-iminium bromide.

In the cation of the title salt, C20H19N2O+·Br-, the phenyl rings are inclined to one another by 38.38 (8)°, whereas the central phenyl ring and the pyridiniminium ring are almost perpendicular with a dihedral angle of 87.37 (9)°. The N+=C cationic double bond was verified by the shortened bond length of 1.337 (2) Å. In the crystal, the Br- anion is linked to the cation by an N-H⋯Br hydrogen bond. C-H⋯O hydrogen bonds link adjacent pyridiniminium cations into inversion dimers with an R22(18) graph-set motif. These dimers are stacked in a phen-yl-phenyl T-shaped geometry through C-H⋯π inter-actions. A Hirshfeld surface analysis was conducted to verify the contributions of the different inter-molecular inter-actions.