Synthesis of Novel Nitro-Halogenated Aryl-Himachalene Sesquiterpenes from Atlas Cedar Oil Components: Characterization, DFT Studies, and Molecular Docking Analysis against Various Isolated Smooth Muscles.

We report the synthesis of two novel halogenated nitro-arylhimachalene derivatives: 2-bromo-3,5,5,9-tetramethyl-1-nitro-6,7,8,9-tetrahydro-5H-benzo[7]annulene (bromo-nitro-arylhimachalene) and 2-chloro-3,5,5,9-tetramethyl-1,4-dinitro-6,7,8,9-tetrahydro-5H-benzo[7]annulene (chloro-dinitro-arylhimachalene). These compounds were derived from arylhimachalene, an important sesquiterpene component of Atlas cedar essential oil, via a two-step halogenation and nitration process. Characterization was performed using 1H and 13C NMR spectrometry, complemented by X-ray structural analysis. Quantum chemical calculations employing density functional theory (DFT) with the Becke3-Lee-Yang-parr (B3LYP) functional and a 6-31++G(d,p) basis set were conducted. The optimized geometries of the synthesized compounds were consistent with X-ray structure data. Frontier molecular orbitals and molecular electrostatic potential (MEP) profiles were identified and discussed. DFT reactivity indices provided insights into the compounds' behaviors. Moreover, Hirshfeld surface and 2D fingerprint analyses revealed significant intermolecular interactions within the crystal structures, predominantly H-H and H-O contacts. Molecular docking studies demonstrate strong binding affinities of the synthesized compounds to the active site of protein 7B2W, suggesting potential therapeutic applications against various isolated smooth muscles and neurotransmitters.

A novel phosphate with CoII square planar coordination, BaCo0.5Fe(PO4)2: structural and magnetic features.

A novel phosphate containing barium, cobalt, and iron was synthesized in single-crystal and polycrystalline forms. Single crystal-based X-ray measurements revealed that it crystallizes in the monoclinic system with the P21/c space group. The structure is made up of linkages between FeO6 octahedra, CoO4 square planar units, CoO5 square pyramidal units, and PO4 tetrahedra through edges and/or vertices. The interconnection of these polyhedra leads to a three-dimensional framework with tunnels along the a-axis where the Ba2+ cations are located. The polycrystalline form was prepared via the sol-gel method and its XRD pattern was refined by the Le Bail method. Morphological and elemental mapping analyses of this phosphate were performed by scanning electron microscopy. In addition, infrared and Raman spectroscopy provided more insights into chemical bonding. The magnetic behavior was antiferromagnetic below TN ∼ 20 K. Optical measurements revealed a direct bandgap with an energy Eg of 2.83 eV.

Crystal structure of barium dinickel(II) iron(III) tris-[orthophosphate(V)], BaNi2Fe(PO4)3.

The orthophosphate BaNi2Fe(PO4)3 has been synthesized by a solid-state reaction route and characterized by single-crystal X-ray diffraction and energy-dispersive X-ray spectroscopy. The crystal structure comprises (100) sheets made up of [Ni2O10] dimers that are linked to two PO4 tetra-hedra via common edges and vertices and of linear infinite [010] chains of corner-sharing [FeO6] octa-hedra and [PO4] tetra-hedra. The linkage of the sheets and chains into a framework is accomplished through common vertices of PO4 tetra-hedra and [FeO6] octa-hedra. The framework is perforated by channels in which positionally disordered Ba2+ cations are located.

Crystal structure reinvestigation and spectroscopic analysis of tricadmium orthophosphate.

Single crystals of tricadmium orthophosphate, Cd3(PO4)2, have been synthesized successfully by the hydro-thermal route, while its powder form was obtained by a solid-solid process. The corresponding crystal structure was determined using X-ray diffraction data in the monoclinic space group P21/n. The crystal structure consists of Cd2O8 or Cd2O10 dimers linked together by PO4 tetra-hedra through sharing vertices or edges. Scanning electron microscopy (SEM) was used to investigate the morphology and to confirm the chemical composition of the synthesized powder. Infrared analysis corroborates the presence of isolated phosphate tetra-hedrons in the structure. UV-Visible studies showed an absorbance peak at 289 nm and a band gap energy of 3.85 eV, as determined by the Kubelka-Munk model.

Crystal growth, structure elucidation and CHARDI/BVS investigations of ß-KCoFe(PO4)2.

Single crystals of ß-KCoFe(PO4)2, potassium cobalt(II) iron(III) bis-(ortho-phosphate), were grown from the melt under atmospheric conditions. This phosphate crystallizes isotypically with KZnFe(PO4)2 in space group C2/c, adopting a zeolite-ABW type of structure. The structure of the present phosphate is distinguished by an occupational disorder of the two transition-metal sites with ratios Fe:Co of 0.5725:0.4275 for the first and 0.4275:0.5725 for the second site. In the crystal structure, PO4 and (Co,Fe)O4 tetra-hedra are linked through vertices to form elliptical rings with the sequence DDDDUUUU of up (U) and down (D) pointing vertices. Each eight-membered ring is surrounded by four other rings of the same type, delimiting inter-stices with rectangular shape. This arrangement leads to the formation of [(Co/Fe)(PO4)]- ∞ sheets parallel to (001). Stacking of the sheets into a three-dimensional framework results in the formation of two types of channels. The first one is occupied by potassium cations, whereas the second one remains vacant. Calculations of bond-valence sums and charge distribution were used to confirm the structure model.

Novel Hydrazono-2-Iminothiazolidin-4-Ones Based on a Monoterpenic Skeleton as Potential Antitumor Agents: Synthesis, DFT Studies, in†Vitro Cytotoxicity, Apoptosis Inducing Properties and Molecular Docking.

A series of novel 2-iminothiazolidin-4-one analogs have been synthesized from limonaketone, and structurally characterized by HR-MS, 1 H-NMR and 13 C-NMR spectroscopy techniques, and the structure of compound 4 was elucidated by XRD. The newly synthesized products were biologically evaluated in vitro for their cytotoxic activity against human cancer cell lines HT-1080, A549, and MCF-7. Thiazolidinones 9 and 10 were the most active compounds in HT-1080 cell lines (IC50 =15.85±1.75 and 16.13±1.55 µM, respectively). The apoptosis induction of the derivatives 9 and 10 were studied using annexin V staining, caspase-3/7 activity and cell cycle analysis. Compound 10 showed the highest ability of apoptosis induction and caspase-3/7 activation associated with S-phase growth arrest in HT-1080. Meanwhile, compound 9 has a moderate apoptotic effect and G0/G1-phase arrest in the after-mentioned cell. The molecular docking suggested that compounds 9 and 10 formed stable ligand-caspase-3 complexes. Besides, the presence of phenyl moiety in ligand 10 is responsible for the enhancement of the caspase-3 activation by the apparition of two additional hydrogen bonds with Cys163 and Gln161amino acids.

Synthesis, crystal structure and Hirshfeld surface analysis of dimethyl 3-(3-bromo-phen-yl)-6-methyl-7-oxo-3,5,6,7-tetra-hydro-pyrazolo-[1,2-a]pyrazole-1,2-di-carboxyl-ate.

The title compound, C17H17BrN2O5, resulted from the 1,3-dipolar cyclo-addition reaction between dimethyl acetyl-enedi-carboxyl-ate and (3-bromo-benzyl-idene)-4-methyl-5-oxopyrazolidin-2-ium-1-ide in CHCl3. The dihedral angle between the pyrazole rings (all atoms) is 32.91 (10)°; the oxo-pyrazole ring displays an envelope conformation whereas the other pyrazole ring adopts a twisted conformation. The bromo-phenyl ring subtends a dihedral angle of 88.95 (9)° with the mean plane of its attached pyrazole ring. In the crystal, the mol-ecules are linked by C-H⋯O hydrogen bonds and aromatic π-π inter-actions with an inter-centroid distance of 3.8369 (10) Å. The Hirshfeld surface analysis and fingerprint plots reveal that the mol-ecular packing is governed by H⋯H (37.1%), O⋯H/H⋯O (31.3%), Br⋯H/H⋯Br (13.5%) and C⋯H/H⋯C (10.6%) contacts. The energy framework indicates that dispersion energy is the major contributor to the mol-ecular packing.

Ultrasound-assisted one-pot three-component synthesis of new isoxazolines bearing sulfonamides and their evaluation against hematological malignancies.

In the present study, following a one-pot two-step protocol, we have synthesized novel sulfonamides-isoxazolines hybrids (3a-r) via a highly regioselective 1,3-dipolar cycloaddition. The present methodology capitalized on trichloroisocyanuric acid (TCCA) as a safe and ecological oxidant and chlorinating agent for the in-situ conversion of aldehydes to nitrile oxides in the presence of hydroxylamine hydrochloride, under ultrasound activation. These nitrile oxides could be engaged in 1,3-dipolar cycloaddition reactions with various alkene to afford the targeted sulfonamides-isoxazolines hybrids (3a-r). The latter were assessed for their antineoplastic activity against model leukemia cell lines (Chronic Myeloid Leukemia, K562 and Promyelocytic Leukemia, HL-60).

Synthesis, crystal structure determination of a novel phosphate Ag1.64Zn1.64Fe1.36(PO4)3 with an alluaudite-like structure.

Single crystals of Ag1.64Zn1.64Fe1.36(PO4)3 [silver zinc iron phosphate (1.64/1.64/1.36/3)] have been synthesized by a conventional solid-state reaction and structurally characterized by single-crystal X-ray diffraction. The title compound crystallizes with an alluaudite-like structure. All atoms of the structure are in general positions except for four, which reside on special positions of the space group, C2/c. The Ag+ cations reside at full occupancy on inversion centre sites and at partial occupancy (64%) on a twofold rotation axis. In this structure, the unique Fe3+ ion with one of the two Zn2+ cations are substitutionally disordered on the same general position (Wyckoff site 8f), with a respective ratio of 0.68/0.32 (occupancies were fixed so as to ensure electrical neutrality for the whole structure). The remaining O and P atoms are located in general positions. The three-dimensional framework of this structure consists of kinked chains of edge-sharing octa-hedra stacked parallel to [10]. These chains are built up by a succession of [MO6] (M = Zn/Fe or Zn) units. Adjacent chains are connected by the PO4 anions, forming sheets oriented perpendicular to [010]. These inter-connected sheets generate two types of channels parallel to the c axis, in which the Ag+ cations are located. The validity and adequacy of the proposed structural model of Ag1.64Zn1.64Fe1.36(PO4)3 was established by means of bond-valence-sum (BVS) and charge-distribution (CHARDI) analysis tools.

Antiproliferative and apoptotic activity of new indazole derivatives as potential anticancer agents.

To develop potent and selective anticancer agents, a series of novel polysubstituted indazoles was synthesized and evaluated for their in vitro antiproliferative and apoptotic activities against two selected human cancer cell lines (A2780 and A549). Several compounds showed an interesting antiproliferative activity, with IC50 values ranging from 0.64 to 17 µM against both cell lines. The most active indazoles were then tested in different pharmacological dilution conditions, adding five new cell lines (A2780, A549, IMR32, MDA-MB-231, and T47D) as targets, confirming their antiproliferative activity. Furthermore, selected compounds were able to trigger apoptosis to a significant extent and to cause, in part, a block of cells in the S phase of the cell cycle, with a concomitant decrease of cells in the G2/M and/or G0/G1 phases and the generation of hypodiploid peaks. However, molecule 7d caused a great increase of cells in G2/M and the appearance of polyploid cells. Altogether, our results suggest a good pharmacological activity for our selected polysubstituted indazoles, which are suggestive of a preferential mechanism of action as cell cycle-specific antimetabolites or as an inhibitor of enzyme activities involved in DNA synthesis, except for 7d, which, on the contrary, seems to have a mechanism involving the microtubule system.

Crystal structure of SrCo4(OH)(PO4)3, a new hy-droxy-phosphate.

Single crystals of strontium tetra-cobalt tris-(orthophosphate) hydroxide, SrCo4(OH)(PO4)3, were grown serendipitously under hydro-thermal conditions at 473 K. The crystal structure consists of undulating chains of edge-sharing [CoO6] octa-hedra that are linked into (010) layers by common vertices between chains. Adjacent layers are linked along [010] into a framework structure by tetra-hedral [CoO4] units and by PO4 tetra-hedra. The framework delimits channels extending along [100] in which the eleven-coordinate strontium cations are situated. Bifurcated O-H⋯O hydrogen bonds of weak strengths consolidate the crystal packing. The title compound was also characterized by infrared spectroscopy.

Crystal structure and Hirshfeld surface analysis of (C7H9N4O2)[ZnCl3(H2O)].

In the title mol-ecular salt, 1,3-dimethyl-2,6-dioxo-2,3,6,7-tetra-hydro-1H-purin-9-ium aqua-tri-chlorido-zincate(II), (C7H9N4O2)[ZnCl3(H2O)], the fused ring system of the cation is close to planar, with the largest deviation from the mean plane being 0.037 (3) Å. In the complex anion, the ZnII cation is coordinated by three chloride ions and one oxygen atom from the water ligand in a distorted tetra-hedral geometry. In the crystal, inversion dimers between pairs of cations linked by pairwise N-H⋯O hydrogen bonds generate R 2 2(10) rings. The anions are linked into dimers by pairs of O-H⋯Cl hydrogen bonds and the respective dimers are linked by O-H⋯O and N-H⋯Cl hydrogen bonds. Together, these generate a three-dimensional supra-molecular network. Hirshfeld surfaces were generated to gain further insight into the packing.

Synthesis and crystal structure of NaCuIn(PO4)2.

Single crystals of sodium copper(II) indium bis-[phosphate(V)], NaCuIn(PO4)2, were grown from the melt under atmospheric conditions. The title phosphate crystallizes in the space group P21/n and is isotypic with KCuFe(PO4)2. In the crystal, two [CuO5] trigonal bipyramids share an edge to form a dimer [Cu2O8] that is connected to two PO4 tetra-hedra. The obtained [Cu2P2O12] units are inter-connected through vertices to form sheets that are sandwiched between undulating layers resulting from the junction of PO4 tetra-hedra and [InO6] octa-hedra. The two types of layers are alternately stacked along [101] and are joined into a three-dimensional framework through vertex- and edge-sharing, leaving channels parallel to the stacking direction. The channels host the sodium cations that are surrounded by four oxygen atoms in form of a distorted disphenoid.

Crystal structure and Hirshfeld surface analysis of 4-allyl-2-meth-oxy-6-nitro-phenol.

The asymmetric unit of the title compound, C10H11NO4, which was synthesized via nitration reaction of eugenol (4-allyl-2-meth-oxy-phenol) with a mixture of nitric acid and sulfuric acid, consists of three independent mol-ecules of similar geometry. Each mol-ecule displays an intra-molecular hydrogen bond involving the hydroxide and the nitro group forming an S(6) motif. The crystal cohesion is ensured by inter-molecular C-H⋯O hydrogen bonds in addition to π-π stacking inter-actions between the aromatic rings [centroid-centroid distances = 3.6583 (17)-4.0624 (16) Å]. The Hirshfeld surface analysis and the two-dimensional fingerprint plots show that H⋯H (39.6%), O⋯H/H⋯O (37.7%), C⋯H/H⋯C (12.5%) and C⋯C (4%) are the most important contributors towards the crystal packing.

Crystal structure of silver strontium copper orthophosphate, AgSr4Cu4.5(PO4)6.

Crystals of the new compound, AgSr4Cu4.5(PO4)6, were grown successfully by the hydro-thermal process. The asymmetric unit of the crystal structure of the title compound contains 40 independent atoms (4 Sr, 4.5 Cu, 1 Ag, 6 P and 24 O), which are all in general positions except for one Cu atom, which is located on an inversion centre. The Cu atoms are arranged in CuO n (n = 4 or 5) polyhedra, linked through common oxygen corners to build a rigid three-dimensional motif. The connection of these copper units is assured by PO4 tetra-hedra. This arrangement allows the construction of layers extending parallel to the (100) plane and hosts suitable cavities in which Ag+ and Sr2+ cations are located. The crystal-structure cohesion is ensured by ionic bonds between the silver and strontium cations and the oxygen anions belonging to two adjacent sheets. Charge-distribution analysis and bond-valence-sum calculations were used to validate the structural model.

Ethyl 10α-hy-droxy-4,9-dimethyl-14-oxo-3,8,15-trioxa-tetra-cyclo-[10.3.0.02,4.07,9]penta-decane-13-spiro-5'-pyrazole-3'-carboxyl-ate.

The ten-membered ring in the title mol-ecule, C25H29ClN2O7, adopts an approximate chair-chair conformation, whereas the five-membered furan and pyrazole rings display envelope conformations. The mean plane of the furan ring is almost perpendicular to that of the pyrazole ring, as indicated by the dihedral angle between them of 86.45 (9)°. The pyrazole ring is slightly inclined to the plane of the attached phenyl ring, subtending a dihedral angle of 16.88 (8)°. The conformation of the mol-ecule is stabilized by six intra-molecular hydrogen bonds and crystal cohesion is ensured by five C-H⋯O hydrogen bonds, in addition to C-H⋯π inter-actions.

Crystal structure and Hirshfeld surface analysis of bis-[hydrazinium(1+)] hexa-fluorido-silicate: (N2H5)2SiF6.

In the title inorganic mol-ecular salt, (N2H5)2SiF6, the silicon atom at the centre of the slightly distorted SiF6 octa-hedron [range of Si-F distances = 1.6777 (4)-1.7101 (4) Å] lies on a crystallographic inversion centre. In the crystal, the ions are connected by N-H⋯N and N-H⋯F hydrogen bonds; the former link the cations into [010] chains and the latter (some of which are bifurcated or trifurcated) link the ions into a three-dimensional network. The two-dimensional fingerprint plots show that F⋯H/H⋯F inter-actions dominate the Hirshfeld surface (75.5%) followed by H⋯H (13.6%) and N⋯H/H⋯N (8.4%) whereas F⋯F (1.9%) and F⋯N/N⋯F (0.6%) have negligible percentages. The title compound is isostructural with its germanium-containing analogue.

Synthesis, crystal structure and Hirshfeld surface analysis of 2-chloro-3-[(E)-(2-phenyl-hydrazinyl-idene)meth-yl]quinoline.

A new quinoline-based hydrazone, C16H12ClN3, was synthesized by a condensation reaction of 2-chloro-3-formyl-quinoline with phenyl-hydrazine. The quinoline ring system is essentially planar (r.m.s. deviation = 0.012 Å), and forms a dihedral angle of 8.46 (10)° with the phenyl ring. The mol-ecule adopts an E configuration with respect to the central C=N bond. In the crystal, mol-ecules are linked by a C-H⋯π-phenyl inter-action, forming zigzag chains propagating along the [10] direction. The N-H hydrogen atom does not participate in hydrogen bonding but is directed towards the phenyl ring of an adjacent mol-ecule, so linking the chains via weak N-H⋯π inter-actions to form of a three-dimensional structure. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions to the crystal packing are from H⋯H (35.5%), C⋯H/H⋯C (33.7%), Cl⋯H/H⋯Cl (12.3%), N⋯H/H⋯N (9.5%) contacts.

Two new glaserite-type orthovanadates: Rb2KDy(VO4)2 and Cs1.52K1.48Gd(VO4)2.

The crystal structures of dirubidium potassium dysprosium bis-(vanadate), Rb2KDy(VO4)2, and caesium potassium gadolinium bis-(vanadate), Cs1.52K1.48Gd(VO4)2, were solved from single-crystal X-ray diffraction data. Both compounds, synthesized by the reactive flux method, crystallize in the space group P m1 with the glaserite structure type. VO4 tetra-hedra are linked to DyO6 or GdO6 octa-hedra by common vertices to form sheets stacking along the c axis. The large twelve-coordinate Cs+ or Rb+ cations are sandwiched between these layers in tunnels along the a and b axes, while the K+ cations, surrounded by ten oxygen atoms, are localized in cavities.

Crystal structure, spectroscopic characterization and Hirshfeld surface analysis of trans-di-aqua-[2,5-bis-(pyridin-4-yl)-1,3,4-oxa-diazole]di-thio-cyanato-nickel(II).

The reaction of 2,5-bis-(pyridin-4-yl)-1,3,4-oxa-diazole (4-pox) and thio-cyanate ions, used as co-ligand with nickel salt NiCl2·6H2O, produced the title complex, [Ni(NCS)2(C12H8N4O)2(H2O)2]. The NiII atom is located on an inversion centre and is octa-hedrally coordinated by four N atoms from two ligands and two pseudohalide ions, forming the equatorial plane. The axial positions are occupied by two O atoms of coordinated water mol-ecules. In the crystal, the mol-ecules are linked into a three-dimensional network through strong O-H⋯N hydrogen bonds. Hirshfeld surface analysis was used to investigate the inter-molecular inter-actions in the crystal packing.