Structural, Theoretical Analysis, and Molecular Docking of Two Benzamide Isomers. Halogen Bonding and Its Role in the Diverse Ways of Coupling with Protein Residues.

The crystal structures of two methoxyphenylbenzamide isomers are described, (Ph2Br) and (Ph3Br), with the general formula C14H12BrNO2. This structural study revealed the presence of N-H-O and C-H-O hydrogen bonds, Br-Br halogen bonds, C-H-π, and C-Br-π molecular contacts, showing in both compounds, a central C1-C7(O1)-N1(H1)-C8 amide segment, to be almost linear. The close proximity between the Br1 and O1 in Ph2Br showed that its interatomic distance was less than the sum of their VDW radii, generating an increase in the electrostatic potential in the O1 region, making possible the appearance of the so-called σ and π-holes on bromine. These specific conditions give rise to the formation of the Br-Br halogens bonds, which are united in a very interesting way, allowing the bond to extend by joining halogen atoms between different molecules forming an isosceles triangle with Br-Br distances equal to 3.5403(4) Å and 5.085 Å as its base. The presence of the carbonyl group in Ph2Br, an excellent acceptor of hydrogen and halogen bonds, led to competition between these bonds to organize crystal growth. The analysis of the compounds as pharmacophores showed that the bromine atom plays a key role in interactions with protein residues, reaching good ligand-protein interaction values comparable to the values presented by the parent inhibitor, Asciminib. In contact with the ALA356 residue, the bromine of Ph2Br participates with a higher contact geometry using the σ-hole, whereas the bromine of Ph3Br employs a more efficient contact geometry by taking advantage of its π-hole.

3,4-Di-methyl-phenyl benzoate.

In the title compound, C15H14O2, the terminal rings form a dihedral angle of 52.39 (4)°. The mean plane of the central ester group [r.m.s. deviation = 0.0488 Å] is twisted away from the benzene and phenyl rings by 60.10 (4) and 8.67 (9)°, respectively. In the crystal, mol-ecules are linked by weak C-H⋯O hydrogen bonds, forming C(6) chains which run along [100].

4-Formyl-2-nitro-phenyl benzoate.

In the title nitroaryl benzoate derivative, C14H9NO5, the aromatic rings form a dihedral angle of 46.37 (8)°. The central ester moiety, -C-(C=O)-O-, is essentially planar (r.m.s. deviation for all non-H atoms = 0.0283 Å) and forms a dihedral angle of 54.06 (9)° with the 4-formyl-2-nitro-phenyl ring and 7.99 (19)° with the benzoate ring. In the crystal, mol-ecules are inter-twined by weak C-H⋯O inter-actions, forming helical chains along [100].

4-Bromo-N-(2-nitro-phen-yl)benzamide.

The title nitro-phenyl benzamide, C13H9BrN2O3, with two mol-ecules in the asymmetric unit, has dihedral angles of 16.78 (15) and 18.87 (14)° between the benzene rings. An intra-molecular N-H⋯O hydrogen bond is observed in each mol-ecule. In the crystal, the molecules are linked by weak C-H⋯O inter-actions; halogen-halogen inter-actions are also observed [Br⋯Br = 3.4976 (7) Å]. These inter-actions form R (2) 2(10), R (2) 2(15) and R (6) 6(32) edge-fused rings along [010].

N-(2-Nitro-phen-yl)thio-phene-2-carbox-amide.

The title compound, C11H8N2O3S, shows two mol-ecules per asymmetric unit, with the dihedral angles between the benzene and thio-phene rings of 13.53 (6) and 8.50 (5)° being a notable difference between them. An intra-molecular N-H⋯O hydrogen-bond in each mol-ecule generates an S(6) ring motif. The crystal packing shows no classical hydrogen bonds with the mol-ecules being packed to form weak C-H⋯O and C-H⋯S inter-actions leading to R 2 (2)(9) and R 4 (4)(25) rings which are edge-shared, giving layers parallel to (010).

4-Formyl-2-nitro-phenyl 3-nitro-2-methyl-benzoate.

In the title formyl nitro aryl benzoate derivative, C15H10N2O7, the benzene rings form a dihedral angle of 4.96 (3)°. The mean plane of the central ester group, C-O-C-(=O)-C (r.m.s. deviation = 0.0484 Å), is twisted away from the formyl nitro aryl and benzoate rings by 46.61 (5) and 49.93 (5)°, respectively. In the crystal, the mol-ecules are packed forming C-H⋯O inter-actions in chains which propagate along [010]. Edge-fused R (3) 3(15) rings are generated along this direction.

Crystal structure of 2-nitro-N-(5-nitro-1,3-thia-zol-2-yl)benzamide.

In the title compound, C10H6N4O5S, the mean plane of the non-H atoms of the central amide fragment C-N-C(=O)-C [r.m.s. deviation = 0.0294 Å] forms dihedral angles of 12.48 (7) and 46.66 (9)° with the planes of the thia-zole and benzene rings, respectively. In the crystal, mol-ecules are linked by N-H⋯O hydrogen bonds, forming chains along [001]. In addition, weak C-H⋯O hydrogen bonds link these chains, forming a two-dimensional network, containing R (4) 4(28) ring motifs parallel to (100).

Crystal structure of 4-bromo-N-(2-hydroxy-phen-yl)benzamide.

In the title compound, C13H10BrNO2, the mean plane of the non-H atoms of the central amide C-N-C(=O)-C fragment (r.m.s. deviation = 0.004 Å) forms a dihedral angle of 73.97 (12)° with the hy-droxy-substituted benzene ring and 25.42 (19)° with the bromo-substituted benzene ring. The two aromatic rings are inclined to one another by 80.7 (2)°. In the crystal, mol-ecules are linked by O-H⋯O and N-H⋯O hydrogen bonds, forming chains along [010]. The chains are linked by weak C-H⋯O hydrogen bonds, forming sheets parallel to (100), and enclosing R (3) 3(17) and R (3) 2(9) ring motifs.

2-[(1-Oxidopyridin-4-yl)sulfan-yl]benzoic acid.

In the title compound, C12H9NO3S, the dihedral angle between the pyridine and benzene rings is 83.93 (7)°. In the crystal, pairs of O-H⋯O hydrogen bonds link the molecules, forming inversion dimers with graph-set notation R 2 (2)(22). These dimers are in turn linked by weak C-H⋯O hydrogen bonds along [100], forming R 2 (2)(8) rings.

2,4,6-Tri-nitro-phenyl 3-bromo-benzoate.

In the title picryl-substituted ester, C13H6BrN3O8, the mean plane of the central ester C-O-C(=O)-C fragment (r.m.s. deviation= 0.0186 Å) is rotated by 84.73 (7)° and 19.92 (12)° to the picryl and phenyl rings, respectively. In the crystal, the mol-ecules are linked by C-H⋯O inter-actions, forming centrosymmetric dimers enclosing R (2) 2(10) and R (2) 2(22) ring motifs along [001] and further helical chains of dimers enclosing R (2) 2(10) ring motifs along [010].

3-(Di-phenyl-amino)-isobenzo-furan-1(3H)-one.

In the title isobenzo-furan-one derivative, C20H15NO2, the planar fused-ring system (r.m.s. deviation for the 10 fitted atoms = 0.031 Å) forms dihedral angles of 63.58 (6) and 63.17 (8)° with the N-bound phenyl rings; the dihedral angle between the planes of these phenyl rings is 85.92 (7)°. In the crystal, mol-ecules are linked by weak C-H⋯O inter-actions, involving both O atoms, forming helical supra-molecular chains along [001].

2,2'-(1,4-Phenyl-ene)bis-(propane-2,2-di-yl) bis-(benzodi-thio-ate).

The title compound, C26H26S4, shows a dihedral angle of 76.64 (15)° between the central and peripheral benzene rings. An inversion center is located at the centroid of the thio-benzoyl ring. In the crystal, weak C-H⋯S inter-actions form C(5) chains along [001]. There are no classical hydrogen bonds.

Crystal structure of (±)-3-[(benzo[d][1,3]dioxol-5-yl)meth-yl]-2-(3,4,5-tri-meth-oxy-phen-yl)-1,3-thia-zolidin-4-one.

In the title thia-zolidine-4-one derivative, C20H21NO6S, the central thia-zolidine ring is essentially planar (r.m.s. deviation for all non-H atoms = 0.0287 Å) and forms a dihedral angle of 88.25 (5)° with the meth-oxy-substituted benzene ring and 74.21 (4)° with the 1,3-benzodioxole ring. The heterocyclic ring (with two O atoms) fused to benzene ring adopts an envelope conformation with the non-ring-junction C atom as the flap. In the crystal, the mol-ecules are linked into chains along [001] through weak C-H⋯O inter-actions, forming R (4) 4(28) edge-fused rings.

Supramolecular study, Hirshfeld analysis and theoretical study of 6-methoxyquinoline N-oxide dihydrate.

In the crystal structure of 6-methoxyquinoline N-oxide dihydrate, C10H9NO2·2H2O, (I), the presence of two-dimensional water networks is analysed. The water molecules form unusual water channels, as well as two intersecting mutually perpendicular columns. In one of these channels, the O atom of the N-oxide group acts as a bridge between the water molecules. The other channel is formed exclusively by water molecules. Confirmation of the molecular packing was performed through the analysis of Hirshfeld surfaces, and (I) is compared with other similar isoquinoline systems. Calculations of bond lengths and angles by the Hartree-Fock method or by density functional theory B3LYP, both with 6-311++G(d,p) basis sets, are reported, together with the results of additional IR, UV-Vis and theoretical studies.

2,4,6-Tri-nitro-phenyl 4-bromo-benzoate.

In the title benzoate derivative, C13H6BrN3O8, the benzene rings form a dihedral angle of 80.90 (9)°. The ester moiety forms dihedral angles of 3.2 (2) and 82.8 4(10)° with the benzene and picryl rings, respectively. The Br atom is disordered over two positions, with the site occupancy for the minor component being 0.48 (4). The crystal structure features C-H⋯O inter-actions, which generate a three-dimensional network.

2,4,6-Tri-nitro-phenyl furan-2-carboxyl-ate.

In the title carboxyl-ate derivative, C11H5N3O9, the picryl ring forms an angle of 75.79 (7)° with the ester fragment, indicating a near perpendicular disposition. The nitro substituents are variously oriented with respect to the picryl ring [dihedral angles = 3.22 (10), 16.03 (12) and 36.63 (10)°]. In the crystal, mol-ecules form helical chains sustained by C-H⋯O inter-actions along [010]. The furanyl residue is disordered, having two coplanar slightly displaced orientations [major component = 0.730 (9)].

2,4,6-Tri-nitro-phenyl 3-chloro-benzoate.

In the title benzoate derivative, C13H6ClN3O8, the planes of the benzene rings form a dihedral angle of 73.59 (7)°. The central ester unit forms an angle of 20.38 (12)° with the chloro-substituted benzene ring. In the crystal, mol-ecules are linked by weak C-H⋯O inter-actions, forming helical chains along [101] and [100].

2,2'-(Carbono-thio-yldisulfanedi-yl)bis-(2-methyl-propanoic acid).

The mol-ecular structure of the title compound, C9H14O4S3, exhibits intra-molecular C-H⋯S hydrogen bonds. In the crystal, pairs of O-H⋯O hydrogen bonds lead to the formation of centrosymmetric dimers, which are in turn connected by weak C-H⋯O inter-actions. The combination of these inter-actions generates edge-fused R 2 (2)(8) and R 2 (2)(20) rings running along [211].

4-Formyl-2-nitro-phenyl 4-bromo-benzoate.

In the title compound, C14H8BrNO5, the benzene rings form a dihedral angle of 62.90 (7)°. The central ester group is twisted away from the nitro-substituted and bromo-substituted rings by 71.67 (7) and 8.78 (15)°, respectively. The nitro group forms a dihedral angle of 7.77 (16)° with the benzene ring to which it is attached. In the crystal, mol-ecules are linked by weak C-H⋯O inter-actions, forming C(12) chains which run along [001]. Halogen-halogen inter-actions [Br⋯Br = 3.523 (3) Å] within the chains stabilized by C-H⋯O inter-actions are observed.

4-Formyl-2-nitro-phenyl 2-chloro-benzoate.

In the title compound, C14H8ClNO5, the benzene rings form a dihedral angle of 19.55 (9)°. The mean plane of the central ester group [r.m.s. deviation = 0.024 Å] forms dihedral angles of 53.28 (13) and 36.93 (16)°, respectively, with the nitro- and chloro-substituted rings. The nitro group forms a dihedral angle of 19.24 (19)° with the benzene ring to which it is attached. In the crystal, mol-ecules are linked by weak C-H⋯O hydrogen bonds, forming C(7) chains, which run along [100].