Synthesis, structural, multitargeted molecular docking analysis of anti-cancer, anti-tubercular, DNA interactions of benzotriazole based macrocyclic ligand.

Biologically important macromolecule 1, 1', 3, 3' Bis - [2,3,5,6-Tetramethyl-p-phenylenebis(methylene)] dibenzotriazlinium dibromide hydrate (BTD) was synthesized and characterized using FT-IR, NMR and single-crystal XRD (SCXRD). SCXRD revealed that the compound was crystallized as a monoclinic system and associated through weak intermolecular interactions like H-bonding and π- π stacking interactions. These weak intermolecular interactions in BTD were studied using Crystal Explorer and Gaussian. The calculated energies for the Highest Occupied Molecular Orbital (HOMO) and the Lowest Unoccupied Molecular Orbital (LUMO) showed the stability and reactivity of the title compound. Molecular electrostatic potential (MEP) surface analysis was used to investigate the crystal's nucleophilic and electrophilic reactive sites. The molecular shape and intermolecular interactions in the crystal structure were determined using Hirshfeld surface analysis and fingerprint plots. Anticancer, anti-bacterial and DNA binding ability of BTD were investigated by experimental and theoretical techniques. The obtained results suggest that BTD possesses better anti-cancer, anti-bacterial and DNA binding abilities. The mode of action of antibiotic and anticancer approach was discussed. This provides promising therapeutic advantages for further development.

Synthesis, molecular docking, and in silico ADMET studies of 4-benzyl-1-(2,4,6-trimethyl-benzyl)-piperidine: Potential Inhibitor of SARS-CoV2.

Nowadays, over 200 countries face a wellbeing emergency because of epidemiological disease COVID-19 caused by the SARS-CoV-2 virus. It will cause a very high effect on the world's economy and the worldwide health sector. The present work is an investigation of the newly synthesized 4-benzyl-1-(2,4,6-trimethyl-benzyl)-piperidine (M1BZP) molecule's inhibitory potential against important protein targets of SARS-CoV-2 using computational approaches. M1BZP crystallizes in monoclinic type with P1211 space group. For the title compound M1BZP, spectroscopic characterization like 1H NMR, 13C NMR, FTIR, were carried out. The geometry of the compound had been optimized by the DFT method and its results were compared with the X-ray diffraction data. The calculated energies for the Highest Occupied Molecular Orbital (HOMO) and the Lowest Unoccupied Molecular Orbital (LUMO) showed the stability and reactivity of the title compound. Intermolecular interactions in the crystal network were determined using Hirshfeld surface analyses. The molecular electrostatic potential (MEP) picture was drawn using the same level of theory to visualize the chemical reactivity and charge distribution on the molecule. Molecular docking study performed for the synthesized compound revealed an efficient interaction with the COVID-19 protease and resulted in good activities. We hope the present study would help workers in the field to develop potential vaccines and therapeutics against the novel coronavirus. Virtual ADME studies were carried out as well and a relationship between biological, electronic, and physicochemical qualifications of the target compound was determined. Toxicity prediction by computational technique for the title compound was also carried out.

1-Benzyl-1H-benzotriazole 3-oxide-1-hy-droxy-1H-benzotriazole (1/1).

In the title compound, C(6)H(5)N(3)O·C(13)H(11)N(3)O, the benzo-triazole ring system in the 1-benzyl-1H-benzotriazole 3-oxide (A) mol-ecule is close to being planar (r.m.s. deviation = 0.011 Å); its mean plane forms a dihedral angle of 67.56 (7)° with that of the attached phenyl ring. The benzotriazole ring system in the 1-hy-droxy-benzotriazole (B) mol-ecule is also close to being planar (r.m.s. deviation = 0.010 Å). In the crystal, weak C-H⋯O and C-H⋯π inter-actions are present. The A and B molecules are linked by an O-H⋯N hydrogen bond.

1-Benz-yloxy-1H-benzotriazole.

In the title compound, C(13)H(11)N(3)O, the dihedral angle between the benzotriazole ring system [maximum deviation = 0.027 (16) Å] and the benzene ring is 10.28 (9)°. The C-C-O-N bond adopts an anti conformation [torsion angle = -177.11 (16)°]. In the crystal, the mol-ecules inter-act via weak C-H⋯π inter-actions and aromatic π-π stacking [centroid-to-centroid distance = 3.731 (12) Å].

1-Benzyl-1H-benzotriazole.

In the title compound, C(13)H(11)N(3), the benzotriazole ring system is essentially planar, with a maximum deviation of 0.0173 (18) Å, and forms a dihedral angle of 75.08 (8)Å with the phenyl ring. In the crystal, pairs of weak C-H⋯N hydrogen bonds form inversion dimers. In addition, there are weak C-H⋯π(arene) inter-actions and weak π-π stacking inter-actions, with a centroid-centroid distance of 3.673 (11) Å.

1-Benzyl-1H-benzotriazole 3-oxide monohydrate.

In the title hydrate, C13H11N3O·H2O, the benzotriazole ring system is planar (r.m.s. deviation = 0.007 Å) and is almost orthogonal to the phenyl ring to which it is linked by a methyl-ene group, forming a dihedral angle of 81.87 (15)°. In the crystal, mol-ecules are linked into chains along [001] by O-H⋯O hydrogen bonds. The chains are consolidated into a three-dimensional architecture by C-H⋯O, C-H⋯π and π-π [centroid-centroid distance between the five- and six-membered rings of the benzotriazole ring system = 3.595 (3) Å] inter-actions.

catena-Poly[[(18-crown-6-κO)potassium]-µ-chlorido-[(1H-benzotriazol-1-ol-κN)chloridoplatinum(II)]-µ-(benzotriazol-1-olato-κN:O)].

In the structure of the title compound, [KPt(C(6)H(4)N(3)O)Cl(2)(C(6)H(5)N(3)O)(C(12)H(24)O(6))], the Pt(II) atom is in a distorted square-planar geometry. The crystal structure is consolidated by O-H⋯O hydrogen bonds. The measured crystal was a non-merohedral twin with four components.

Tetra-µ-chlorido-bis-(18-crown-6)platinum(II)dipotassium(I).

In the title compound, [K(2)PtCl(4)(C(12)H(24)O(6))(2)], the Pt(II) ion is located on an inversion centre and is coordinated by four Cl atoms, forming a square-planar geometry. The K(I) ion is coordinated by six O atoms of the crown ether and two bridging Cl atoms. The K(I) ion is displaced by 0.756 (2) Šfrom the mean plane of the six O atoms of the crown ether. The mol-ecules are connected by weak C-H⋯O hydrogen bonds, forming an infinite two-dimensional network parallel to the (10) plane. Intra- and inter-molecular C-H⋯Cl hydrogen bonds are also observed.

catena-Poly[[aqua-sodium(I)]-µ-[2,2'-(disulfanedi-yl)bis-(pyridine N-oxide)]-µ-(pyridine-2-thiol-ato 1-oxide)].

There are two monomeric units in the asymmetric unit of the polymeric title compound, [Na(C(5)H(4)NOS)(C(10)H(8)N(2)O(2)S(2))(H(2)O)](n). The Na(I) ions are six coordinated by four O atoms, one S atom and one water mol-ecule, forming a slightly distorted octa-hedral geometry. An intra-molecular O-H⋯O hydrogen bond stabilizes the conformation of the mol-ecule. The crystal packing is consolidated by inter-molecular O-H⋯O, O-H⋯N and O-H⋯S hydrogen bonds, π-π inter-actions [with centroid-centroid distances of 3.587 (2) Å] together with weak C-H⋯π inter-actions. The mol-ecules are linked into polymeric chains along the b-axis direction.

1-Mesitylmethyl-1Hbenzotriazole 3-oxide.

In the title compound, C(16)H(17)N(3)O, the benzotriazole ring forms a dihedral angle of 77.25 (6)° with the phenyl ring. The benzotriazole ring is essentially planar with a maximum deviation of 0.012 (19) Å. Weak inter-molecular C-H⋯O hydrogen bonds form R(2) (2)(10) motifs. The crystal packing is consolidated by π-π inter-actions with centroid-centroid distances of 3.5994 (12) Štogether with very weak C-H⋯π inter-actions.

4-Aminopyridinium 4-aminobenzoate dihydrate and 4-aminopyridinium nicotinate.

In the title compounds, 4-aminopyridinium 4-aminobenzoate dihydrate, C(7)H(6)NO(2)(-).C(5)H(7)N(2)(+).2H(2)O, (I), and 4-aminopyridinium nicotinate, C(5)H(7)N(2)(+).C(6)H(4)NO(2)(-), (II), the aromatic N atoms of the 4-aminopyridinium cations are protonated. In (I), the asymmetric unit is composed of two 4-aminopyridinium cations, two 4-aminobenzoate anions and four water molecules, and the compound crystallizes in a noncentrosymmetric space group. The two sets of independent molecules of (I) are related by a centre of symmetry which is not part of the space group. In (I), the protonated pyridinium ring H atoms are involved in bifurcated hydrogen bonding with carboxylate O atoms to form an R(1)(2)(4) ring motif. The water molecules link the ions to form a two-dimensional network along the (101) plane. In (II), an intramolecular bifurcated hydrogen bond generates an R(1)(2)(4) ring motif and inter-ion hydrogen bonding generates an R(4)(2)(16) ring motif. The packing of adduct (II) is consolidated via N-H...O and N-H...N hydrogen bonds to form a two-dimensional network along the (102) plane.

Tetra-aqua-bis[3-(2-pyridylsulfan-yl)propionato N-oxide]nickel(II).

In the centrosymmetric title compound, [Ni(C(8)H(8)NO(3)S)(2)(H(2)O)(4)], the Ni(II) ion, which lies on an inversion centre, is six coordinated by four water mol-ecules and two propionate O atoms from two 2-pyridylsulfanylpropionate N-oxide ligands, forming a slightly distorted octa-hedral geometry. An intra-molecular O-H⋯O hydrogen bond stabilizes the mol-ecular conformation. The crystal packing is consolidated by inter-molecular O-H⋯O and C-H⋯O hydrogen bonding.

1-(2,3,5,6-Tetra-methyl-benz-yloxy)-1H-benzotriazole.

In the title compound, C(17)H(19)N(3)O, the benzotriazole ring is essentially planar, with a maximum deviation of 0.0069 (15) Å. The mean plane of the benzotriazole ring forms a dihedral angle of 13.16 (4)° with the mean plane of the benzene ring. The crystal packing is stabilized by π-π stacking inter-actions, with a centroid-centroid distance of 3.8077 (12) Å, together with weak C-H⋯π inter-actions. Mol-ecules are stacked along the a axis.

1,1'-[2,3,5,6-Tetra-methyl-p-phenyl-ene-bis(methyl-eneoxy)]di-1H-benzotriazole.

The complete molecule of the title compound, C(24)H(24)N(6)O(2), is generated by a crystallographic inversion centre. The benzotriazole rings form dihedral angles of 2.10 (7)° with the central aromatic ring. The crystal packing is consolidated by π-π inter-actions, with centroid-centroid distances of 3.6234 (10) Å, together with weak C-H⋯π inter-actions.

Bis(4-amino-pyridinium) tetra-chlorido-cobaltate(II).

In the title compound, (C(5)H(7)N(2))(2)[CoCl(4)], the cobalt(II) ion is coordinated by four chloride ions in a slightly distorted tetra-hedral geometry. The crystal packing is stabilized by inter-molecular N-H⋯Cl hydrogen bonding, forming a three-dimensional network. The crystal was a non-merohedral twin emulating tetra-gonal symmetry, but being in fact ortho-rhom-bic.

2-(Mesitylmethylsulfanyl)pyridine N-oxide monohydrate.

In the title compound, C(15)H(17)NOS·H(2)O, the benzene and pyridine rings form a dihedral angle of 71.18 (2)°. The intra-molecular S⋯O distance [2.737 (3) Å] is shorter than expected and, in terms of hybridization principles, the N-C-S angle [114.1 (2)°] is smaller than expected. The crystal structure is stabilized by inter-molecular O-H⋯O and weak C-H⋯O hydrogen bonds. In addition, weak π-π stacking inter-actions with a centroid-centroid distance of 3.778 (3) Šare also observed.

2-(2,3,5,6-Tetra-methyl-benzyl-sulfan-yl)pyridine N-oxide.

In the title compound, C(16)H(19)NOS, the durene ring and the oxopyridyl ring form a dihedral angle of 82.26 (7)°. The crystal structure is stabilized by inter-molecular C-H⋯O hydrogen bonds, weak C-H⋯π inter-actions and π-π inter-actions [centroid-centroid distance of 3.4432 (19) Å], together with intra-molecular S⋯O [2.657 (2) Å] short contacts.

cis-Bis(2-sulfidopyridine N-oxide)platinum(II).

In the crystal structure of the title complex, [Pt(C(5)H(4)NOS)(2)], the Pt atom is coordinated by two O atoms and two S atoms in a cis configuration, forming a distorted square-planar coordination geometry. The mol-ecule exhibits pseudo-C(2v) symmetry and is essentially planar, with a maximum deviation from planarity of 0.0124 (2) Å. The dihedral angle between the two pyridine rings is 5.85 (2)°.

2,2'-[2,3,5,6-Tetra-methyl-p-phenyl-ene-bis(methyl-enethio)]bis-(pyridine N-oxide).

Mol-ecules of the title compound, C(22)H(24)N(2)O(2)S(2), lie across centres of inversion. The two thio-pyridine N-oxide groups adopt a stepped trans configuration with respect to the benzene ring, by virtue of the symmetry. The oxopyridinium ring forms a dihedral angle of 79.9 (2)° with the benzene ring. The crystal structure is stabilized by a strong π-π inter-action between the pyridinium rings of adjacent mol-ecules [ring centroid-centroid distance = 3.464 (3) Å].

2-(Benzyl-sulfan-yl)pyridine N-oxide.

In the title compound, C(12)H(11)NOS, the dihedral angle between the oxopyridinium and phenyl rings is 58.40 (1)°. The crystal structure is stabilized by C-H⋯O hydrogen bonds, π-π stacking inter-actions involving the pyridinium rings [centroid-centroid distance = 3.6891 (9) Å] and C-H⋯π inter-actions.