Efficient synthesis and antitumor activity of novel oxazaphosphinane derivatives: X-ray crystallography, DFT study and molecular docking.

A novel potentially biologically active oxazaphosphinane derivatives was synthesized by facile synthetic approaches from the combination of hydroxyaniline, aldehyde, and triethylphosphite. The crystal structure of compound 1b has been determined. Single crystals belong to the triclinic system with p - 1 space. The relative in vitro antitumor activity against human cell lines (PRI, K562, and JURKAT) of these derivatives in comparison to chlorombucil is reported. All synthesized compound showed excellent activity with IC50 value of 0.014-0.035 mM. The binding energy of the Epidermal growth factor receptor (EGFR)-oxazaphosphinane complex and the calculated inhibition constant using docking simulation showed that all molecules has the ability to inhibit EGFR therapeutic target. In addition, DFT calculation has been used to analyze the electronic and geometric characteristics.Communicated by Ramaswamy H. Sarma.

An unexpected single crystal structure of nickel(II) complex: Spectral, DFT, NLO, magnetic and molecular docking studies.

This work explores the study of a synthesized nickel complex as a possible inhibitor against the main protease (Mpro) of the recent emerging coronavirus disease (COVID-19). Overall, the template reaction of 3-acetyl-2-hydroxy-6-methyl-4H-pyran-4-one with nickel(II) chloride hexahydrate in N,N-dimethylformamide (DMF) medium leads to the formation of neutral nickel complex. This resulting complex is formulated as [Ni(DHA)2(DMF)2] on the basis of FT-IR, UV-Vis., single-crystal X-ray diffraction analysis, magnetic susceptibility and CV measurements as well as DFT quantum chemical calculations. Its single crystal suggests was found to be surrounded by the both pairs of molecules of DHA and DMF through six oxygen atoms with octahedral coordination sphere. The obtained magnetic susceptibilities are positive and agree with its paramagnetic state. In addition to the experimental investigations, optimized geometry, spectroscopic and electronic properties were also performed using DFT calculation with B3LYP/6-31G(d,p) level of theory. The nonlinear optical (NLO) properties of this complex are again examined. Some suitable quantum descriptors (EHOMO, ELUMO, Energy gap, Global hardness), Milliken atomic charge, Electrophilic potion and Molecular Electrostatic Potential) have been elegantly described. Molecular docking results demonstrated that the docked nickel complex displayed remarkable binding energy with Mpro. Besides, important molecular properties and ADME pharmacokinetic profiles of possible Mpro inhibitors were assessed by in silico prediction.

Alkali and alkaline earth coordination polymers constructed from benzene-1,2,4,5-tetracarboxylic acid and flexible dicarboxylate acid ligands: syntheses, structures and spectroscopic and thermal properties.

Two new metal coordination complexes, namely, poly[aqua(µ6-benzene-1,2,4,5-tetracarboxylic acid-κ8O1:O1,O2:O2':O4:O4,O5:O5')(µ-but-2-enedioato-κ2O1:O4)potassium(I)], [K2(C4H2O4)(C10H6O8)(H2O)2]n or [K2(fum)(H4btec)(H2O)2]n, (1), and poly[aqua(µ8-2,5-dicarboxybenzene-1,4-dicarboxylato-κ12O1:O1',O2:O2,O2':O2':O4:O4',O5:O5,O5':O5')(µ-ethanedioato-κ4O1,O2:O1',O2')strontium(II)], [Sr2(C2O4)(C10H4O8)(H2O)2]n or [Sr2(ox)(H2btec)(H2O)2]n, (2) (H4btec = benzene-1,2,4,5-tetracarboxylic acid, H2btec = 2,5-dicarboxybenzene-1,4-dicarboxylate, fum = fumarate and ox = oxalate), have been obtained under hydrothermal conditions by reacting the different alkali and alkaline earth metal salts with H4btec, fumaric acid (H2fum) and oxalic acid (H2ox). Complexes (1) and (2) were structurally characterized by single-crystal X-ray diffraction, IR and UV-Vis spectroscopy, powder X-ray diffraction (PXRD) and thermogravimetic analysis-differential scanning calorimetry (TGA-DSC). Complex (1) displays a two-dimensional (2D) layer with the K+ ion in a distorted pentagonal bipyramidal geometry and exhibits a uninodal 6-connected hxl/Shubnikov plane net (3,6) with {36.46.53} topology. Complex (2) displays a three-dimensional (3D) network structure, in which the Sr2+ ion is in a distorted monocapped square antiprism geometry. The framework possess a binodal (5,8)-connected net with the Schläfli symbol {32.410.58.64.74}{32.46.52}2. The 3D Hirshfeld surfaces and 2D fingerprint plots show that the main interactions are the O...H/H...O intermolecular interactions. Moreover, the thermal decompositions of (1) and (2) in the temperature range 303-1273 K revealed that they both decompose in three steps and transform to the corresponding metal oxide.

Mechanistic basis of breast cancer resistance protein inhibition by new indeno[1,2-b]indoles.

The ATP-binding cassette transporter ABCG2 mediates the efflux of several chemotherapeutic drugs, contributing to the development of multidrug resistance (MDR) in many cancers. The most promising strategy to overcome ABCG2-mediated MDR is the use of specific inhibitors. Despite many efforts, the identification of new potent and specific ABCG2 inhibitors remains urgent. In this study, a structural optimization of indeno[1,2-b]indole was performed and a new generation of 18 compounds was synthesized and tested as ABCG2 inhibitors. Most compounds showed ABCG2 inhibition with IC50 values below 0.5 µM. The ratio between cytotoxicity (IG50) and ABCG2 inhibition potency (IC50) was used to identify the best inhibitors. In addition, it was observed that some indeno[1,2-b]indole derivatives produced complete inhibition, while others only partially inhibited the transport function of ABCG2. All indeno[1,2-b]indole derivatives are not transported by ABCG2, and even the partial inhibitors are able to fully chemosensitize cancer cells overexpressing ABCG2. The high affinity of these indeno[1,2-b]indole derivatives was confirmed by the strong stimulatory effect on ABCG2 ATPase activity. These compounds did not affect the binding of conformation-sensitive antibody 5D3 binding, but stabilized the protein structure, as revealed by the thermostabilization assay. Finally, a docking study showed the indeno[1,2-b]indole derivatives share the same binding site as the substrate estrone-3-sulfate.

Synthesis, crystal structure, and thermal properties of poly[aqua-(µ5-2,5-di-carb-oxy-benzene-1,4-di-carboxyl-ato)strontium].

A coordination polymer formulated as [Sr(H2BTEC)(H2O)] n (H4BTEC = benzene-1,2,4,5-tetra-carb-oxy-lic acid, C10H6O8), was synthesized hydro-thermally and characterized by single-crystal and powder X-ray diffraction, scanning electron microscopy and thermal analysis. Its crystal structure is made up of a zigzag inorganic chain formed by edge-sharing of [SrO8] polyhedra running along [001]. Adjacent chains are connected to each other via the carboxyl-ate groups of the ligand, resulting in a double-layered network extending parallel to (100). O-H⋯O hydrogen bonds of medium-to-weak strength between the layers consolidate the three-dimensional structure. One of the carb-oxy-lic OH functions was found to be disordered over two sets of sites with half-occupancy.

Syntheses, supramolecular networks and Hirshfeld surface and thermal analyses of two new cadmium chloride coordination polymers with an N,O-chelating ligand.

Two new coordination polymers, namely poly[[(3-aminopyrazin-4-ium-2-carboxylate-κ2N1,O)di-µ-chlorido-cadmium(II)] monohydrate], {[CdCl2(C5H5N3O2)]·H2O}n, (1), and poly[2-amino-3-carboxypyrazin-1-ium [(3-aminopyrazine-2-carboxylato-κ2N1,O)di-µ-chlorido-cadmium(II)] monohydrate], {(C5H6N3O2)[Cd(C5H4N3O2)Cl2]·H2O}n, (2), have been synthesized from the reaction of cadmium(II) chloride and 3-aminopyrazine-2-carboxylic acid (Hapca) under mild conditions in acidic media. The two coordination polymers have been characterized by single-crystal X-ray diffraction and show chloride-bridged zigzag chains with octahedrally coordinated metal ions, where Hapca acts as a bidentate ligand via the π-conjugated N atom and a carboxylate O atom. The chains are further interconnected via noncovalent interactions into three-dimensional supramolecular networks. The dominant H...O and H...Cl interactions for both compounds were quantified using Hirshfeld surface analysis. The thermal stability and topological analysis of the two-dimensional networks of (1) and (2) are also discussed.

A novel three-dimensional SrII coordination polymer based on benzene-1,2,4,5-tetracarboxylate: hydrothermal synthesis, crystal structure and spectroscopic and thermal studies.

Coordination of the anions of benzenecarboxylic acids with metal cations leads to coordination polymers with various structural features. Very few examples of strontium-based structures have been reported. A new three-dimensional coordination polymer, namely poly[aqua(µ12-benzene-1,2,4,5-tetracarboxylato)distrontium(II)], [Sr2(C10H2O8)(H2O)]n, has been synthesized under hydrothermal conditions and characterized by thermal analysis, vibrational spectroscopy (Raman and IR), single-crystal X-ray diffraction and powder X-ray diffraction. The coordination geometries around the two independent SrII ions can be described as a distorted dodecahedron and a distorted monocapped square antiprism. The compound features a three-dimensional structure containing inorganic motifs, with two-dimensional layers connected through organic linkers, and possesses a topologic structure of a binodal (6,12) connected alb net with the Schläfli symbol {415}2{448.618}. The final product of thermal decomposition is strontium oxide (SrO).

Bis(4-amino-benzene-sulfonamide-κN (4))di-chlorido-zinc.

In the title compound, [ZnCl2(C6H8N2O2S)2], the Zn(II) ion lies on a twofold rotation axis and has a slightly distorted tetra-hedral coordination geometry, involving two Cl atoms and two N atoms from the amino groups attached directly to the benzene rings [Zn-Cl = 2.2288 (16) Šand Zn-N = 2.060 (5) Å]. The dihedral angle between the benzene rings is 67.1 (3)°. The crystal packing can be describe as layers in a zigzag arrangement parallel to (001). The amine H atoms act as donor atoms and participate in inter-molecular N-H⋯O and N-H⋯Cl hydrogen bonds, forming a three-dimensional network.

Bis(3-amino-pyrazine-2-carboxyl-ato-κ(2) N (1),O)di-aqua-nickel(II) dihydrate.

In the title compound, [Ni(C5H4N3O2)2(H2O)2]·2H2O, the Ni(II) ion lies on an inversion center and is coordinated in an slightly distorted octa-hedral environment by two N,O-chelating 3-amino-pyrazine-2-carboxyl-ate (APZC) ligands in the equatorial plane and two trans-axial aqua ligands. In the crystal, O-H⋯O, N-H⋯O and O-H⋯N hydrogen bonds involving the solvent water mol-ecules, aqua and APZC ligands form layers parallel to (010). These layers are linked further via O-H⋯O, N-H⋯O and C-H⋯O hydrogen bonds involving the axial aqua ligands, amino groups and the carboxyl-ate groups of the APZC ligands, forming a three-dimensional network.

1-Chloro-methyl-sulfinyl-2-nitro-benzene.

In the title compound, C(7)H(6)ClNO(3)S, the nitro group forms a dihedral angle of 2.7 (4)° with the benzene ring. The bond-angle sum at the S atom is 303.7°. In the crystal, mol-ecules are linked by weak C-H⋯O hydrogen bonds, forming layers lying parallel to (-101).

(Benzene-carbothio-amide-κS)-penta-carbonyl-tungsten(0).

The asymmetric unit of the title complex, [W(C(7)H(7)NS)(CO)(5)], comprises two independent mol-ecules. In each, the W atom is coordinated by five CO groups and the S atom of the benzencarbothioamide ligand in a distorted octa-hedral geometry. The crystal packing can be described as undulating layers of W(CO)(5) and benzene-carbothio-amide parallel to (001). In the crystal, components are linked via inter-molecular N-H⋯O and C-H⋯O hydrogen bonds to form a dimeric chains along the [010] direction. Intra-molecular N-H⋯C inter-actions are also observed.