CuII Pyrazolyl-Benzimidazole Dinuclear Complexes with Remarkable Antioxidant Activity.

Three dinuclear coordination complexes generated from 1-n-butyl-2-((5-methyl-1H-pyrazole-3-yl)methyl)-1H-benzimidazole (L), have been synthesized and characterized spectroscopically and structurally by single crystal X-ray diffraction analysis. Reaction with iron(II) chloride and then copper(II) nitrate led to a co-crystal containing 78 % of [Cu(NO3 )(µ-Cl)(L')]2 (C1 ) and 22 % of [Cu(NO3 )(µ-NO3 )(L')]2 (C2 ), where L was oxidized to a new ligand L' . A mechanism is provided. Reaction with copper chloride led to the dinuclear complex [Cu(Cl)(µ-Cl)(L)]2 (C3 ). The presence of N-H⋅⋅⋅O and C-H⋅⋅⋅O intermolecular interactions in the crystal structure of C1 and C2 , and C-H⋅⋅⋅N and C-H⋅⋅⋅Cl hydrogen bonding in the crystal structure of C3 led to supramolecular structures that were confirmed by Hirshfeld surface analysis. The ligands and their complexes were tested for free radical scavenging activity and ferric reducing antioxidant power. The complex C1 /C2 shows remarkable antioxidant activities as compared to the ligand L and reference compounds.

Synthesis, X-ray Crystal Structure, Anticancer, Hirshfeld Surface Analysis, DFT, TD-DFT, ADMET, and Molecular Docking of 3-Phenyl-1,2,4-triazolo[3,4-h]-13,4-thiaza-11-crown-4.

In this work, we describe the synthesis of new macrocycles derived from 3-phenyl-1,2,4-triazole-5-thione 1 in a heterogeneous medium using liquid-solid phase transfer catalysis (PTC) conditions. The structures of the two compounds (3 and 4) isolated were elucidated based on spectral data (1H-NMR, 13C-NMR) and confirmed in the case of 3-phenyl-1,2,4-triazolo [3,4-h]-13,4--thiaza-11-crown-4 (3) by a single-crystal X-ray diffraction analysis. Furthermore, the experimental spectral and the X-ray geometrical parameters were compared with their corresponding predicted ones obtained at the B3LYP/6-311++G(d,p) level of theory. The intercontacts between crystal units were investigated through Hirshfeld surface analysis. The drug-like macrocycles were predicted using ADMET and drug-likeness properties, which showed that 3 may act as an inhibitor of DNA-dependent protein kinase (DNA-PK). This assumption was confirmed by the well-binding fitting of 3 into the binding site of DNA-PK and the formation of a stable 3-DNA-PK complex with a binding energy of -7 kcal-mol-1. Finally, the anticancer activity of 3 was assessed by an MTT assay against A549 cells, which showed that 3 has moderate anticancer activity compared to that of the doxorubicin reference drug.

Synthesis, biological activity and molecular modeling of a new series of condensed 1,2,4-triazoles.

A ring transformation of 6-methyl-7H[1,2,4]triazolo [4,3-b][1,2,4] triazepine-8(9H)-ones (thiones) in the presence of acetic anhydride give rise to a new series of 17 condensed 1,2,4-triazole derivatives (1-17). Plausible mechanisms are proposed and show the formation of a beta fused ß-lactam moiety. The compounds were tested for their (i) inhibitory potential on digestive enzymes (α-amylase and α-glucosidase), and (ii) antioxidant activity using radical scavenging (DPPH and ABTS radicals) and ferric reducing power assays. The compounds showed interesting and promising antidiabetic activities compared to the reference drug Acarbose. Molecular docking study has been carried out to determine the binding mode interactions between these derivatives and the targeted enzymes. The results showed the strength of intermolecular hydrogen bonding in ligand-receptor complexes as an important descriptor in rationalizing the observed inhibition results. Moreover, molecular dynamics simulations are also performed for the best protein-ligand complex to understand the stability of small molecule in a protein environment. To shed light on the antioxidant activity of the synthesized compounds and the mechanism involved in DPPH free radical, DFT calculations were performed at the B3P86/6-311++G(d,p) level using the polarizable continuum model. The effect of aprotic solvent on bond dissociation enthalpies (BDEs) is investigated by calculating and comparing BDEs of 1 in methanol and dimethylsulfoxide as solvents using PCM. The obtained results show that the mechanism of action depends on the basic skeleton and the presence of substituted functional groups in these derivatives. BDEs are found to be slightly influenced by the aprotic solvent of less than 0.01 kcal/mol compared with those obtained in methanol.

Concept for simultaneous and specific in situ monitoring of amyloid oligomers and fibrils via Förster resonance energy transfer.

Oligomeric species of amyloidogenic peptides or proteins are often considered as the most toxic species in several amyloid disorders, like Alzheimer or Parkinson's diseases, and hence came into the focus of research interest and as a therapeutic target. An easy and specific monitoring of oligomeric species would be of high utility in the field, as it is the case for thioflavin T fluorescence for the fibrillar aggregates. Here, we show proof of concept for a new sensitive method to increase specific detection of oligomers by two extrinsic fluorophores. This is achieved by exploiting a Förster resonance energy transfer (FRET) between the two fluorophores. Thus, a mixture of two extrinsic fluorophores, bis-ANS and a styrylquinoxalin derivative, enabled one to monitor simultaneously and in situ the presence of oligomers and fibrils of amyloidogenic peptides. Thereby, the formation of oligomers and their transformation into fibrils can be followed.

Palladium-catalyzed direct C7-arylation of substituted indazoles.

A novel direct C7-arylation of indazoles with iodoaryls is described using Pd(OAc)2 as catalyst, 1,10-phenanthroline as ligand, and K2CO3 as base in refluxing DMA. Direct C7-arylation of 3-substituted 1H-indazole containing an EWG on the arene ring gave the expected products in good isolated yields. In addition, a one-pot Suzuki-Miyaura/arylation procedure leading to C3,C7-diarylated indazoles has been developed.

Fostering hydroxyapatite bioactivity and mechanical strength by Si-doping and reinforcing with multiwall carbon nanotubes.

The aim of the present study was to prepare resorbable hydroxyapatite (HA) based bone graft materials reinforced with carbon nanotubes as a way to cope with the inability of pure HA to resorb and its intrinsic brittleness and poor strength that restrict its clinical applications under load-bearing conditions. With this purpose, a Si-doped HA nanopowder (n-Si0.8HA) was prepared by chemical synthesis and used as composite matrix reinforced with different amounts of functionalized multiwall carbon nanotubes (MWCNTs). The effect of the added amounts of MWCNTs on the mechanical properties of nanocomposites and their in vitro biomineralization was assessed by bending strength measurements, immersing tests in simulated body fluid solution (SBF), scanning electron microscopy (SEM), and inductively coupled plasma atomic emission spectroscopy analysis (ICP-AES). The bioactivity and bending strength were enhanced, reaching maximum balanced values for an optimum addition of 3 wt.% f-MWCNTs. These results might contribute to broaden the potential applications of HA-based bone grafts.

Bis(1-benzyl-1H-benzimidazole-κN (3))di-chlorido-zinc.

In the title compound, [ZnCl2(C14H12N2)2], the Zn(II) atom exhibits a distorted tetra-hedral coordination geometry involving two chloride anions and two N-atom donors from 1-benzyl-1H-benzimidazole ligands. In both ligands, the benzyl and benzimidazole rings are nearly perpendicular [dihedral angles = 81.7 (2) and 81.5 (2)°]. The two benzimidazole systems are essentially planar [maximum deviations = 0.015 (3) and 0.020 (2) Å] and form a dihedral angle of 78.09 (8)°. In the crystal, centrosymmetrically related mol-ecules are linked by pairs of C-H⋯Cl hydrogen bonds into chains parallel to the a axis.

Crystal structure of 1-ethyl-pyrazolo[3,4-d]pyrimidine-4(5H)-thione.

In the title compound, C7H8N4S, the methyl C atom is displaced by 1.232 (7) Šfrom the mean plane of the pyrazolo-[3,4-d]pyrimidine ring system (r.m.s. deviation = 0.007 Å). The N-N-C-Cm (m = meth-yl) torsion angle is -60.3 (6)°. In the crystal, mol-ecules are linked by N-H⋯S hydrogen bonds, generating [010] chains, which are reinforced by C-H⋯N inter-actions. The chains are cross-linked by weak C-H⋯S hydrogen bonds, generating (001) sheets.

Crystal structure of 4-allyl-sulfanyl-1H-pyrazolo-[3,4-d]pyrimidine.

In the title compound, C8H8N4S, the pyrazolo-[3,4-d]pyrimidine ring system is essentially planar, with a maximum deviation from the mean plane of 0.025 (3) Å. The allyl group is disordered over two sites in a 0.512 (6):0.488 (6) ratio. In the crystal, mol-ecules are linked by pairs of N-H⋯N hydrogen bonds, forming inversion dimers with an R 2 (2)(8) graph-set motif.

1-[(1-Benzyl-1H-1,2,3-triazol-4-yl)meth-yl]indoline-2,3-dione.

In the title compound, C18H14N4O2, the triazole ring makes dihedral angles of 77.32 (8) and 75.56 (9)°, respectively, with the indoline residue and the terminal phenyl group. In the crystal, mol-ecules are linked by C-H⋯N hydrogen bonds into tapes parallel to the b axis. The tapes are linked together by π-π inter-actions between triazole rings [inter--centroid distance = 3.4945 (9) Å].

(2Z)-2-Benzyl-idene-4-(prop-2-yn-1-yl)-2H-1,4-benzo-thia-zin-3(4H)-one.

The mol-ecule of the title compound, C18H13NOS, is build up from two fused six-membered rings, with the heterocyclic component linked to a benzyl-idene group and to a prop-2-yn-1-yl chain. The six-membered heterocycle adopts a distorted screw-boat conformation. The prop-2-yn-1-yl chain is almost perpendicular to the mean plane through benzo-thia-zine as indicated by the C-N-C-C torsion angle of 86.5 (2)°. The dihedral angle between the benzene rings is 47.53 (12)°. There are no specific inter-molecular inter-actions in the crystal packing.

Ethyl 2-{5-[(3-oxo-3,4-di-hydro-2H-1,4-benzo-thia-zin-4-yl)meth-yl]-1H-1,2,3-triazol-1-yl}acetate.

In the title compound, C15H16N4O3S, the six-membered heterocycle of the benzo-thia-zine fragment exhibits a screw boat conformation. The dihedral angle between the planes through the triazole ring and the benzene ring fused to the 1,4-thia-zine ring is 62.98 (11)°. The mean plane formed by the atoms belonging to the acetate group is nearly perpendicular to the triazole ring [dihedral angle = 74.65 (12)°]. In the crystal, mol-ecules are linked by pairs of C-H⋯O inter-actions, forming dimeric aggregates.

4-[(1-Benzyl-1H-1,2,3-triazol-4-yl)meth-yl]-2H-1,4-benzo-thia-zin-3(4H)-one.

In the title compound, C18H16N4OS, the six-membered heterocycle of the benzo-thia-zine fragment exhibits a screw-boat conformation. The dihedral angles between the plane through the triazole ring and those through the fused and terminal benzene rings are 76.68 (11) and 71.0 (1)°, respectively; the benzene rings are nearly perpendicular [dihedral angle = 79.6 (1)°]. In the crystal, mol-ecules are linked by C-H⋯N and C-H⋯O inter-actions, forming a three-dimensional network.

3-(2,3-Dioxoindolin-1-yl)propane-nitrile.

The asymmetric unit of the title compound, C11H8N2O2, contains two independent mol-ecules (A and B). Each mol-ecule is build up from fused five- and six-membered rings with the former linked to a cyano-ethyl group. The indoline ring and two carbonyl O atoms of each mol-ecule are nearly coplanar, with the largest deviations from the mean planes being 0.0198 (9) (mol-ecule A) and 0.0902 (9) Š(mol-ecule B), each by a carbonyl O atom. The fused ring system is nearly perpendicular to the mean plane passing through the cyano-ethyl chains, as indicated by the dihedral angles between them of 69.72 (9) (mol-ecule A) and 69.15 (9)° (mol-ecule B). In the crystal, mol-ecules are linked by C-H⋯O and π-π [inter-centroid distance between inversion-related indoline (A) rings = 3.6804 (7) Å] inter-actions into a double layer that stacks along the a-axis direction.

4-[(1-Benzyl-1,2,3-triazol-5-yl)meth-yl]-2H-1,4-benzo-thia-zin-3(4H)-one.

The asymmetric unit of the title compound, C18H16N4OS, contains two independent mol-ecules of similar conformation, the most relevant difference being the dihedral angle formed by the benzene rings [57.8 (2) and 52.7 (2)°]. The six-membered heterocycle of the benzo-thia-zine fragment exhibits a screw-boat conformation in both mol-ecules. The plane through the triazole ring is nearly perpendicular to those through the fused and terminal benzene rings [dihedral angles of 74.2 (2) and 83.2 (2)° in one mol-ecule, and 77.8 (2) and 82.9 (2)° in the other]. In the crystal, mol-ecules are linked by C-H⋯N and C-H⋯O hydrogen bonds into chains parallel to the a-axis direction. The crystal used was a non-merohedral twin, the refined ratio of twin components being 0.85 (10):15 (10).

Crystal structure of 1-methyl-4-methyl-sulfanyl-1H-pyrazolo-[3,4-d]pyrimidine.

In the title compound, C7H8N4S, the non-H atoms of the pyrazolo-[3,4-d]pyrimidine ring system and the methyl-sulfanyl group lie on a crystallographic mirror plane. In the crystal, mol-ecules are linked via a number of π-π inter-actions [centroid-centroid distances vary from 3.452 (7) to 3.6062 (8) Å], forming a three-dimensional structure.

4-(Prop-2-yn-yl)-2H-1,4-benzo-thia-zin-3(4H)-one.

In the title compound, C11H9NOS, the six-membered heterocycle of the benzo-thia-zine fragment exhibits a screw-boat conformation. The benzene ring makes a dihedral angle of 79.4 (1)° with the mean plane through the prop-2-ynyl chain and the ring N atom. In the crystal, mol-ecules are linked by C-H⋯O inter-actions of the acetyl-enic C-H group towards the carbonyl O atom of a neighbouring mol-ecule, forming zigzag chains running along the b-axis direction.

(2Z)-2-Benzyl-idene-4-n-butyl-3,4-di-hydro-2H-1,4-benzo-thia-zin-3-one.

In the title compound, C19H19NOS, the six-membered hetero-cyclic ring of the benzo-thia-zine fragment exhibits a screw boat conformation. The plane of the fused benzene ring makes a dihedral angle of 72.38 (12)° with that of the terminal phenyl ring, and is nearly perpendicular to the mean plane formed by the atoms through the n-butyl chain, as indicated by the dihedral angle of 88.1 (2)°. In the crystal, mol-ecules are linked by C-H⋯O inter-actions to form supra-molecular chains along [110].

Synthesis, crystal structure and Hirshfeld surface analysis of 1-[3-(2-oxo-3-phenyl-1,2-di-hydro-quinoxalin-1-yl)prop-yl]-3-phenyl-1,2-di-hydro-quinoxalin-2-one.

In the title compound, C31H24N4O2, the di-hydro-quinoxaline units are both essentially planar with the dihedral angle between their mean planes being 64.82 (4)°. The attached phenyl rings differ significantly in their rotational orientations with respect to the di-hydro-quinoxaline planes. In the crystal, one set of C-H⋯O hydrogen bonds form chains along the b-axis direction, which are connected in pairs by a second set of C-H⋯O hydrogen bonds. Two sets of π-stacking inter-actions and C-H⋯π(ring) inter-actions join the double chains into the final three-dimensional structure.

Crystal structure and Hirshfeld surface analysis of 3-phenyl-1-{3-[(3-phenyl-quinoxalin-2-yl)-oxy]prop-yl}-1,2-di-hydro-quinoxalin-2-one.

In the title compound, C31H24N4O2, the quinoxaline units are distinctly non-planar and twisted end-to-end. In the crystal, C-H⋯O and C-H⋯N hydrogen bonds link the mol-ecules into chains extending along the a-axis direction. The chains are linked through π-stacking inter-actions between inversion-related quinoxaline moieties.