Crystal structure and mol­ecular docking study of diethyl 2,2′-({[(1E,1′E)-(hydrazine-1,2-diyl­idene)bis­(methanylyl­idene)]bis­(4,1-phenyl­ene)}bis­(­oxy))di­acetate

Daoui, S.; Kansiz, S.; Aktas, F.A.; Dege, N.; Saif, E.; Benchat, N.; Karrouchi, K.

doi:10.1107/S205698902101344X

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ISSN: 2056-9890

Volume 78| Part 1| January 2022| Pages 88-91

https://doi.org/10.1107/S205698902101344X

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Crystal structure and molecular docking study of diethyl 2,2′-({[(1E,1′E)-(hydrazine-1,2-diylidene)bis(methanylylidene)]bis(4,1-phenylene)}bis(oxy))diacetate

Said Daoui,^a ^* Sevgi Kansiz,^b ^* Feyzi Alkim Aktas,^c Necmi Dege,^d Eiad Saif,^e,^f ^* Noureddine Benchat ^a and Khalid Karrouchi ^g

^aLaboratory of Applied Chemistry and Environment (LCAE), Faculty of Sciences, Mohammed I University, 60000 Oujda, Morocco, ^bSamsun University, Faculty of Engineering, Department of Fundamental Sciences, 55420, Samsun, Turkey, ^cSamsun University, Faculty of Engineering, Biomedical Engineering, Samsun, 55420, Turkey, ^dOndokuz Mayıs University, Faculty of Arts and Sciences, Department of Physics, 55139, Samsun, Turkey, ^eDepartment of Computer and Electronic Engineering Technology, Sanaa Community College, Sanaa, Yemen, ^fDepartment of Electrical and Electronic Engineering, Faculty of Engineering, Ondokuz Mayıs University, 55139, Samsun, Turkey, and ^gLaboratory of Analytical Chemistry and Bromatology, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Morocco
^*Correspondence e-mail: saiddaouilabo2017@gmail.com, sevgi.kansiz@samsun.edu.tr, eiad.saif@scc.edu.ye

Edited by A. Briceno, Venezuelan Institute of Scientific Research, Venezuela (Received 11 November 2021; accepted 19 December 2021; online 1 January 2022)

The title Schiff base, C₂₂H₂₄N₂O₆, adopts an E configuration. The molecule is planar, the mean planes of the phenyl ring system (r.m.s deviation = 0.0059 Å) forms a dihedral angle of 0.96 (4)° with the mean plane of the phenyl ring moiety (r.m.s deviation = 0.0076 Å). In the crystal, molecules are linked by weak intermolecular C—H⋯O and C—H⋯N hydrogen bonds into chains extending along the c-axis and b-axis directions, respectively. A molecular docking study between the title molecule and 5-HT2C, which is a G protein receptor and ligand-gated ion channels found in nervous systems (PDB ID: 6BQH) was executed. The experiment shows that it is a good potential agent because of its affinity and ability to stick to the active sites of the receptor.

Keywords: crystal structure; Schiff base; hydrazine; molecular docking.

CCDC reference: 2129693

1. Chemical context

Compounds with an azomethine group (–C=N–) are known as Schiff bases, which are usually synthesized from the condensation of active carbonyl groups and primary amines (Yang et al., 2001 ). Furthermore, these derivatives represent an important class of organic compounds, especially in the medicinal and pharmaceutical fields (Murtaza et al., 2014 ). It is well known from the literature that Schiff bases display excellent biological properties, such as antioxidant and analgesic (Karrouchi et al., 2016 ), antibacterial and cytotoxic (Maaref et al., 2020 ), antidiabetic (Karrouchi et al., 2022 ) and anti-inflammatory activities (Rana et al., 2012 ). These derivatives are also used as corrosion inhibitors, which relies on their ability to spontaneously form a monolayer on the surface being protected (El Arrouji et al., 2020 ). In this study, the title compound, diethyl 2,2′-({[(1E,1′E)-(hydrazine-1,2-diylidene)bis(methanylylidene)]bis(4,1-phenylene)}bis(oxy))diacetate, was characterized by single crystal X-ray and studied by Hirshfeld surface analysis.

2. Structural commentary

The molecular structure of the title compound is illustrated in Fig. 1. The asymmetric unit contains one independent molecule, which is planar, the mean plane of the C5–C10 phenyl ring (r.m.s deviation = 0.006 Å) forms a dihedral angle of 0.96 (4)° with the mean plane of the C16–C20 phenyl ring (r.m.s deviation = 0.008 Å). The C3—O1 and C14—O4 bond lengths in the molecule are 1.213 (8) and 1.212 (8) Å, respectively, while the C11—N1 and C22—N2 bond lengths are 1.274 (7) and 1.275 (7) Å, respectively (Table 1). These results suggest a double-bond character for the C=O and C=N bonds. The N1—N2 bond distance, 1.419 (7) Å, is compatible with 1.411 Å (Manawar et al., 2019 ; Kansiz et al., 2021 ). These results suggest a single bond character for N—N, as expected from hydrazine structures. The exocyclic angles C4—C3—O2 [115.4 (6)°], O1—C3—O2 [125.4 (8)°], C15—C14—O4 [125.5 (7)°] and C15—C14—O5 [111.9 (6)°] deviate significantly from the normal value of 120°; this may be due to steric repulsion (H4A⋯H10 = 2.22 Å and H15B⋯H17 = 2.32 Å). Bond lengths and angles are within normal ranges and are comparable to those observed in related structures (see Database survey section).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C6—H6⋯O4ⁱ	0.93	2.57	3.483 (9)	169
C4—H4B⋯N1ⁱⁱ	0.97	2.69	3.618 (10)	161
Symmetry codes: (i) $[-x, y+{\script{1\over 2}}, -z-{\script{3\over 2}}]$ ; (ii) .

Figure 1
The molecular structure of the title compound, with atom labelling. Displacement ellipsoids are drawn at the 40% probability level.

3. Supramolecular features

In the crystal, there are two intermolecular hydrogen bonds. The C6—H6⋯O4ⁱ hydrogen bond links the molecules to each other along the c-axis direction while the C4—H4B⋯N1ⁱⁱ hydrogen bond links the molecules to each other along the b-axis direction (symmetry codes as in Table 1). A view of the crystal packing is shown in Fig. 2.

Figure 2
The crystal packing of the title compound with the intermolecular C—H⋯O hydrogen bonds shown as dashed lines.

4. Database survey

A search of the Cambridge Structural Database (CSD, version 5.42, update of May 2021; Groom et al., 2016 ) for the ethyl 2-(p-tolyloxy)acetate skeleton revealed seven similar compounds, viz.: ethyl 4-[1-(4-bromophenyl)-3-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-4-yliminomethyl]phenoxyacetate (EKEYEY; Thamotharan et al., 2003 ), di[3-fluoro-6-methoxy-4-(ethoxycarbonylmethoxy)benzyl] ether (HIGLEP; Wallner et al., 2007 ), ethyl (2-fluoro-4-hydroxymethyl-5-methoxyphenoxy)acetate (HIGLIT; Wallner et al., 2007), diethyl 3,3-bis{3-[4-(2-ethoxy-2-oxoethoxy)-3-methoxyphenyl]acryloyl}pentanedioate (JUMJEI; Xu et al., 2015 ), ethyl (4-{3-[2,4-bis(2-ethoxy-2-oxoethoxy)phenyl]-3-oxoprop-1-en-1-yl}phenoxy)acetate (PIXWAW; Liu, 2014 ), ethyl [(2-oxo-2H-chromen-7-yl)oxy]acetate (WIHDEY; Fun et al., 2013 ) and ethyl {4-[(E)-2-(3,4,5-trimethoxyphenyl)vinyl]phenoxy}acetate (XEWZIJ; Baolin et al., 2007 ). In EKEYEY, the ethoxycarbonylmethoxy group is oriented at an angle of 29.42 (15)° with respect to the mean plane of the benzene ring. The mean plane of the 2H-chromene ring system (O1/C1–C9, r.m.s deviation = 0.026 Å) forms a dihedral angle of 81.71 (6)° with the mean plane of ethyl 2-hydroxyacetate moiety (O1/N3/C9/C10, r.m.s deviation = 0.026 Å) in WIHDEY. This dihedral angle for the title compound is smaller than in both EKEYEY and WIHDEY with a value of 4.38 (8)°. The C10—C11 bond distance of 1.516 (2) Å in WIHDEY, corresponding to a single bond, is slightly longer than observed for the title compound [C3—C4 = 1.498 (10) Å]. This bond length is also longer than in XEWZIJ [C18–C19 = 1.493 (3) Å; Baolin et al., 2007)].

5. Molecular docking study

Molecular docking is a substantial process for finding the interactions between small molecules and macromolecules. Intermolecular bonds that occur between ligand and receptor are indicated by molecular docking. In this study, AutoDockVina (Trott & Olson, 2010 ) was used for predictive binding sites between the title molecule and the 5-HT2C receptor (Peng et al., 2018 ). 6BQH is a serotonin receptor, which can be efficient for designing drugs to treat ailments such as anxiety, aggression, sleep disorders, and other psychological diseases. The three-dimensional structure of 6BQH was taken from the Protein Data Bank (PDB). Before the docking calculations, the receptor must be prepared for efficient insertion. For this reason, all water and ligand molecules were cleared on receptor active sites. According to these active sites, grid box dimensions were defined as 100 x 80 x 110 Å. In addition, –x, y, z centres were adjusted to be −40.569, 33.142, 45.392, respectively, and then the 5-HT2C receptor was saved in PDBQT format for the calculations. In the next step, rotatable angles for the coupling structure were determined and recorded in PDBQT format. Discovery Studio Visualizer (Biovia, 2017 ) was used for observations and preparations. All docking calculations were calculated with AutoDockVina. Twenty variable links were decided by AutoDockVina for the ligands connected to the receptor of the protein. The best affinity energy was observed in the first calculation, which is −6.2 kcal mol⁻¹. The bonding type of interaction is represented in Fig. 3. The 2D and 3D visuals of the intermolecular interactions for the best binding pose of the title compound docked into macromolecule 6BQH can be seen in Fig. 4. In addition, docking conformation can be seen in Fig. 5. Consequently, the title compound could be a possible molecule for drug design to treat psychological disorders, because its ability is suitable to stick to active sites of the receptor.

Figure 3
Three-dimensional visual of the intermolecular interactions for the best binding pose of the title compound docking with 6BQH.

Figure 4
Two-dimensional visual of the intermolecular interactions for the best binding pose of the title compound docking with 6BQH.

Figure 5
Three-dimensional conformation of the title compound with 6BQH.

6. Synthesis and crystallization

Hydrazine hydrate (0.013 g, 0.24 mmol) was added dropwise to a solution of ethyl 2-(4-formylphenoxy)acetate (0.5 g, 0.48 mmol) in ethanol (20 ml), and the mixture was refluxed for 4 h. After cooling, the solvent was removed under reduced pressure, and the residue was purified by recrystallization from ethanol to afford single crystals (yield 80%).

7. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. C-bound H atoms were positioned geometrically and refined using a riding model with C—H = 0.93–0.97 Å and U_iso(H) = 1.5U_eq(C) for methyl H atoms, and U_iso(H) = 1.2U_eq(C) for all other H atoms. The crystal studied was refined as a two-component inversion twin, but the absolute structure was indeterminate.

Table 2
Experimental details

Crystal data
Chemical formula	C₂₂H₂₄N₂O₆
M_r	412.43
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	296
a, b, c (Å)	8.1864 (4), 9.2061 (5), 27.7903 (18)
V (Å³)	2094.4 (2)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.10
Crystal size (mm)	0.68 × 0.44 × 0.22

Data collection
Diffractometer	Stoe IPDS 2
Absorption correction	Integration (X-RED32; Stoe & Cie, 2002 )
T_min, T_max	0.945, 0.979
No. of measured, independent and observed [I > 2σ(I)] reflections	11156, 4091, 2453
R_int	0.037
(sin θ/λ)_max (Å⁻¹)	0.617

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.073, 0.246, 1.01
No. of reflections	4091
No. of parameters	254
No. of restraints	2
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.50, −0.67
Absolute structure	Refined as an inversion twin, but the absolute structure was indeterminate
Absolute structure parameter	−1 (4)
Computer programs: X-AREA and X-RED (Stoe & Cie, 2002), SHELXT2017/1 (Sheldrick, 2015a ), SHELXL2017/1 (Sheldrick, 2015b ), PLATON (Spek, 2020 ) and WinGX (Farrugia, 2012 ).

Supporting information

CCDC reference: 2129693

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S205698902101344X/zn2012sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S205698902101344X/zn2012Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S205698902101344X/zn2012Isup3.cml

checkCIF report

Computing details top

Data collection: X-AREA (Stoe & Cie, 2002); cell refinement: X-AREA (Stoe & Cie, 2002); data reduction: X-RED (Stoe & Cie, 2002); program(s) used to solve structure: SHELXT2017/1 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2017/1 (Sheldrick, 2015b); molecular graphics: PLATON (Spek, 2020); software used to prepare material for publication: WinGX (Farrugia, 2012).

Diethyl 2,2'-({[(1E,1'E)-(hydrazine-1,2-diylidene)bis(methanylylidene)]bis(4,1-phenylene)}bis(oxy))diacetate top

Crystal data top

C₂₂H₂₄N₂O₆	D_x = 1.308 Mg m⁻³
M_r = 412.43	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P2₁2₁2₁	Cell parameters from 9754 reflections
a = 8.1864 (4) Å	θ = 2.2–27.8°
b = 9.2061 (5) Å	µ = 0.10 mm⁻¹
c = 27.7903 (18) Å	T = 296 K
V = 2094.4 (2) Å³	Prism, colorless
Z = 4	0.68 × 0.44 × 0.22 mm
F(000) = 872

Data collection top

Stoe IPDS 2 diffractometer	4091 independent reflections
Radiation source: sealed X-ray tube, 12 x 0.4 mm long-fine focus	2453 reflections with I > 2σ(I)
Detector resolution: 6.67 pixels mm^-1	R_int = 0.037
rotation method scans	θ_max = 26.0°, θ_min = 2.3°
Absorption correction: integration (X-RED32; Stoe & Cie, 2002)	h = −8→10
T_min = 0.945, T_max = 0.979	k = −11→11
11156 measured reflections	l = −27→34

Refinement top

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F² > 2σ(F²)] = 0.073	w = 1/[σ²(F_o²) + (0.1576P)²] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.246	(Δ/σ)_max < 0.001
S = 1.00	Δρ_max = 0.50 e Å⁻³
4091 reflections	Δρ_min = −0.67 e Å⁻³
254 parameters	Absolute structure: Refined as an inversion twin
2 restraints	Absolute structure parameter: −1 (4)

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. Refined as a 2-component inversion twin.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
O6	0.4659 (6)	−0.4221 (5)	−0.88303 (18)	0.0861 (14)
O3	−0.9934 (5)	−0.3444 (5)	−0.61477 (18)	0.0815 (13)
N2	−0.1980 (6)	−0.3968 (4)	−0.76468 (19)	0.0658 (12)
O2	−1.2412 (6)	−0.2842 (6)	−0.5611 (2)	0.0968 (15)
N1	−0.3161 (6)	−0.3494 (5)	−0.73078 (19)	0.0671 (13)
O4	0.7008 (8)	−0.4943 (6)	−0.9435 (2)	0.122 (2)
O5	0.8443 (9)	−0.2982 (8)	−0.9259 (3)	0.145 (2)
O1	−1.3702 (7)	−0.4910 (7)	−0.5761 (2)	0.123 (2)
C19	0.0707 (7)	−0.3464 (5)	−0.7945 (2)	0.0587 (13)
C8	−0.5825 (7)	−0.4041 (5)	−0.7005 (2)	0.0590 (13)
C3	−1.2583 (9)	−0.4068 (9)	−0.5824 (3)	0.090 (2)
C5	−0.8617 (7)	−0.3742 (6)	−0.6434 (2)	0.0659 (15)
C16	0.3406 (8)	−0.3906 (6)	−0.8529 (2)	0.0656 (15)
C11	−0.4446 (7)	−0.4275 (5)	−0.7311 (2)	0.0618 (14)
H11	−0.448969	−0.504718	−0.752671	0.074*
C9	−0.7122 (7)	−0.5040 (6)	−0.7029 (2)	0.0689 (15)
H9	−0.705537	−0.581369	−0.724270	0.083*
C18	0.2009 (7)	−0.2516 (5)	−0.7937 (2)	0.0655 (15)
H18	0.198036	−0.172160	−0.773028	0.079*
C17	0.3358 (7)	−0.2717 (6)	−0.8230 (2)	0.0677 (15)
H17	0.421932	−0.205814	−0.822424	0.081*
C10	−0.8487 (7)	−0.4902 (6)	−0.6743 (2)	0.0677 (15)
H10	−0.931717	−0.558927	−0.675966	0.081*
C22	−0.0682 (7)	−0.3205 (5)	−0.7625 (2)	0.0617 (14)
H22	−0.061751	−0.246143	−0.739922	0.074*
C20	0.0776 (9)	−0.4663 (5)	−0.8255 (2)	0.0710 (16)
H20	−0.009621	−0.530867	−0.827039	0.085*
C6	−0.7324 (8)	−0.2740 (6)	−0.6404 (2)	0.0764 (17)
H6	−0.739197	−0.196246	−0.619141	0.092*
C21	0.2131 (8)	−0.4884 (6)	−0.8537 (2)	0.0756 (17)
H21	0.218970	−0.569887	−0.873361	0.091*
C4	−1.1264 (9)	−0.4449 (8)	−0.6175 (3)	0.0857 (19)
H4A	−1.086821	−0.542135	−0.610821	0.103*
H4B	−1.171001	−0.444297	−0.649865	0.103*
C7	−0.5976 (8)	−0.2901 (6)	−0.6684 (2)	0.0711 (16)
H7	−0.513326	−0.222775	−0.665958	0.085*
C14	0.7176 (9)	−0.3829 (8)	−0.9207 (3)	0.0848 (19)
C15	0.6016 (8)	−0.3258 (7)	−0.8849 (3)	0.0785 (17)
H15A	0.653522	−0.320003	−0.853552	0.094*
H15B	0.565809	−0.229246	−0.894006	0.094*
C12	0.9676 (12)	−0.3616 (12)	−0.9585 (5)	0.145 (2)
H12A	1.024040	−0.440591	−0.942466	0.175*
H12B	0.914541	−0.400186	−0.986975	0.175*
C13	1.0808 (13)	−0.2527 (12)	−0.9718 (4)	0.145 (2)
H13A	1.161245	−0.293458	−0.993055	0.218*
H13B	1.024480	−0.175271	−0.987935	0.218*
H13C	1.133662	−0.215559	−0.943555	0.218*
C2	−1.3727 (13)	−0.2480 (11)	−0.5256 (4)	0.139 (3)
H2A	−1.381933	−0.323663	−0.501410	0.167*
H2B	−1.477161	−0.237448	−0.541630	0.167*
C1	−1.3215 (13)	−0.1070 (10)	−0.5029 (4)	0.139 (3)
H1A	−1.401592	−0.077904	−0.479592	0.209*
H1B	−1.217725	−0.119369	−0.487328	0.209*
H1C	−1.312388	−0.033665	−0.527309	0.209*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O6	0.080 (3)	0.089 (3)	0.089 (3)	0.000 (2)	0.019 (3)	−0.013 (2)
O3	0.069 (3)	0.093 (3)	0.082 (3)	−0.014 (2)	0.010 (2)	−0.004 (2)
N2	0.066 (3)	0.055 (2)	0.076 (3)	0.001 (2)	−0.002 (3)	−0.001 (2)
O2	0.077 (3)	0.097 (3)	0.117 (4)	0.014 (3)	0.032 (3)	0.019 (3)
N1	0.063 (3)	0.063 (2)	0.076 (3)	0.001 (2)	0.005 (3)	0.000 (2)
O4	0.132 (5)	0.109 (4)	0.124 (4)	0.004 (4)	0.050 (4)	−0.017 (3)
O5	0.118 (4)	0.160 (4)	0.159 (5)	−0.008 (3)	0.057 (4)	−0.021 (4)
O1	0.091 (4)	0.144 (4)	0.133 (5)	−0.035 (4)	0.027 (4)	0.004 (4)
C19	0.060 (3)	0.051 (2)	0.065 (3)	0.004 (2)	−0.002 (3)	0.002 (2)
C8	0.059 (3)	0.054 (2)	0.064 (3)	0.003 (2)	−0.005 (3)	0.004 (2)
C3	0.071 (5)	0.096 (5)	0.102 (5)	−0.003 (4)	−0.002 (4)	0.034 (4)
C5	0.056 (3)	0.071 (3)	0.071 (4)	0.003 (3)	0.004 (3)	0.008 (3)
C16	0.068 (3)	0.063 (3)	0.066 (4)	0.002 (3)	0.002 (3)	−0.001 (3)
C11	0.066 (4)	0.052 (2)	0.067 (3)	0.005 (2)	−0.010 (3)	0.004 (2)
C9	0.064 (4)	0.064 (3)	0.079 (4)	−0.005 (3)	−0.006 (3)	−0.008 (3)
C18	0.062 (3)	0.056 (3)	0.078 (4)	0.006 (2)	0.001 (3)	−0.005 (3)
C17	0.064 (3)	0.063 (3)	0.077 (4)	−0.002 (3)	−0.004 (3)	−0.003 (3)
C10	0.061 (3)	0.064 (3)	0.078 (4)	−0.016 (3)	−0.001 (3)	−0.007 (3)
C22	0.062 (3)	0.047 (2)	0.076 (4)	−0.002 (2)	−0.002 (3)	−0.003 (2)
C20	0.075 (4)	0.056 (3)	0.082 (4)	−0.006 (3)	−0.001 (4)	−0.001 (3)
C6	0.075 (4)	0.069 (3)	0.085 (4)	−0.003 (3)	0.002 (4)	−0.018 (3)
C21	0.082 (4)	0.062 (3)	0.083 (4)	−0.006 (3)	0.009 (4)	−0.015 (3)
C4	0.079 (5)	0.099 (4)	0.079 (4)	−0.018 (4)	0.004 (4)	0.007 (4)
C7	0.064 (4)	0.060 (3)	0.089 (4)	−0.007 (3)	−0.007 (4)	−0.004 (3)
C14	0.082 (5)	0.089 (4)	0.083 (5)	0.011 (4)	0.017 (4)	−0.004 (4)
C15	0.075 (4)	0.082 (3)	0.078 (4)	−0.001 (3)	0.008 (4)	0.006 (3)
C12	0.118 (4)	0.160 (4)	0.159 (5)	−0.008 (3)	0.057 (4)	−0.021 (4)
C13	0.118 (4)	0.160 (4)	0.159 (5)	−0.008 (3)	0.057 (4)	−0.021 (4)
C2	0.121 (5)	0.146 (5)	0.151 (6)	0.013 (5)	0.061 (5)	0.007 (5)
C1	0.121 (5)	0.146 (5)	0.151 (6)	0.013 (5)	0.061 (5)	0.007 (5)

Geometric parameters (Å, º) top

O6—C16	1.355 (7)	C18—H18	0.9300
O6—C15	1.422 (8)	C17—H17	0.9300
O3—C5	1.367 (7)	C10—H10	0.9300
O3—C4	1.432 (8)	C22—H22	0.9300
N2—C22	1.275 (7)	C20—C21	1.372 (9)
N2—N1	1.419 (7)	C20—H20	0.9300
O2—C3	1.282 (9)	C6—C7	1.359 (9)
O2—C2	1.497 (10)	C6—H6	0.9300
N1—C11	1.274 (7)	C21—H21	0.9300
O4—C14	1.212 (8)	C4—H4A	0.9700
O5—C14	1.306 (9)	C4—H4B	0.9700
O5—C12	1.477 (10)	C7—H7	0.9300
O1—C3	1.213 (8)	C14—C15	1.474 (9)
C19—C18	1.378 (7)	C15—H15A	0.9700
C19—C20	1.403 (8)	C15—H15B	0.9700
C19—C22	1.463 (8)	C12—C13	1.415 (10)
C8—C7	1.382 (8)	C12—H12A	0.9700
C8—C9	1.406 (8)	C12—H12B	0.9700
C8—C11	1.431 (8)	C13—H13A	0.9600
C3—C4	1.498 (10)	C13—H13B	0.9600
C5—C10	1.375 (8)	C13—H13C	0.9600
C5—C6	1.407 (8)	C2—C1	1.502 (10)
C16—C17	1.375 (8)	C2—H2A	0.9700
C16—C21	1.379 (8)	C2—H2B	0.9700
C11—H11	0.9300	C1—H1A	0.9600
C9—C10	1.376 (8)	C1—H1B	0.9600
C9—H9	0.9300	C1—H1C	0.9600
C18—C17	1.385 (8)

C16—O6—C15	118.7 (5)	C20—C21—C16	120.4 (5)
C5—O3—C4	116.0 (5)	C20—C21—H21	119.8
C22—N2—N1	111.5 (5)	C16—C21—H21	119.8
C3—O2—C2	114.9 (6)	O3—C4—C3	111.2 (6)
C11—N1—N2	112.6 (4)	O3—C4—H4A	109.4
C14—O5—C12	112.0 (7)	C3—C4—H4A	109.4
C18—C19—C20	118.5 (5)	O3—C4—H4B	109.4
C18—C19—C22	119.3 (5)	C3—C4—H4B	109.4
C20—C19—C22	122.2 (5)	H4A—C4—H4B	108.0
C7—C8—C9	117.4 (6)	C6—C7—C8	121.6 (6)
C7—C8—C11	124.6 (5)	C6—C7—H7	119.2
C9—C8—C11	118.0 (5)	C8—C7—H7	119.2
O1—C3—O2	125.4 (8)	O4—C14—O5	122.6 (7)
O1—C3—C4	119.2 (8)	O4—C14—C15	125.5 (7)
O2—C3—C4	115.4 (6)	O5—C14—C15	111.9 (6)
O3—C5—C10	125.5 (5)	O6—C15—C14	107.8 (6)
O3—C5—C6	115.3 (5)	O6—C15—H15A	110.1
C10—C5—C6	119.2 (6)	C14—C15—H15A	110.1
O6—C16—C17	124.4 (6)	O6—C15—H15B	110.1
O6—C16—C21	115.1 (5)	C14—C15—H15B	110.1
C17—C16—C21	120.5 (6)	H15A—C15—H15B	108.5
N1—C11—C8	124.2 (5)	C13—C12—O5	109.2 (8)
N1—C11—H11	117.9	C13—C12—H12A	109.8
C8—C11—H11	117.9	O5—C12—H12A	109.8
C10—C9—C8	121.7 (5)	C13—C12—H12B	109.8
C10—C9—H9	119.1	O5—C12—H12B	109.8
C8—C9—H9	119.1	H12A—C12—H12B	108.3
C19—C18—C17	121.6 (5)	C12—C13—H13A	109.5
C19—C18—H18	119.2	C12—C13—H13B	109.5
C17—C18—H18	119.2	H13A—C13—H13B	109.5
C16—C17—C18	119.0 (6)	C12—C13—H13C	109.5
C16—C17—H17	120.5	H13A—C13—H13C	109.5
C18—C17—H17	120.5	H13B—C13—H13C	109.5
C5—C10—C9	119.7 (5)	O2—C2—C1	105.5 (8)
C5—C10—H10	120.2	O2—C2—H2A	110.6
C9—C10—H10	120.2	C1—C2—H2A	110.6
N2—C22—C19	122.0 (5)	O2—C2—H2B	110.6
N2—C22—H22	119.0	C1—C2—H2B	110.6
C19—C22—H22	119.0	H2A—C2—H2B	108.8
C21—C20—C19	120.0 (6)	C2—C1—H1A	109.5
C21—C20—H20	120.0	C2—C1—H1B	109.5
C19—C20—H20	120.0	H1A—C1—H1B	109.5
C7—C6—C5	120.4 (5)	C2—C1—H1C	109.5
C7—C6—H6	119.8	H1A—C1—H1C	109.5
C5—C6—H6	119.8	H1B—C1—H1C	109.5

C22—N2—N1—C11	−177.6 (5)	C20—C19—C22—N2	−7.5 (8)
C2—O2—C3—O1	0.7 (11)	C18—C19—C20—C21	1.1 (8)
C2—O2—C3—C4	−179.3 (7)	C22—C19—C20—C21	−177.9 (6)
C4—O3—C5—C10	0.8 (9)	O3—C5—C6—C7	−177.8 (6)
C4—O3—C5—C6	179.7 (5)	C10—C5—C6—C7	1.2 (9)
C15—O6—C16—C17	−1.0 (9)	C19—C20—C21—C16	−2.3 (9)
C15—O6—C16—C21	179.3 (5)	O6—C16—C21—C20	−178.5 (6)
N2—N1—C11—C8	179.8 (5)	C17—C16—C21—C20	1.8 (9)
C7—C8—C11—N1	3.4 (9)	C5—O3—C4—C3	176.2 (5)
C9—C8—C11—N1	−176.4 (5)	O1—C3—C4—O3	−171.2 (6)
C7—C8—C9—C10	−0.4 (8)	O2—C3—C4—O3	8.8 (9)
C11—C8—C9—C10	179.4 (5)	C5—C6—C7—C8	0.0 (10)
C20—C19—C18—C17	0.6 (8)	C9—C8—C7—C6	−0.4 (9)
C22—C19—C18—C17	179.6 (5)	C11—C8—C7—C6	179.8 (5)
O6—C16—C17—C18	−179.8 (5)	C12—O5—C14—O4	−5.3 (13)
C21—C16—C17—C18	−0.1 (9)	C12—O5—C14—C15	174.9 (8)
C19—C18—C17—C16	−1.1 (9)	C16—O6—C15—C14	−178.8 (5)
O3—C5—C10—C9	176.9 (6)	O4—C14—C15—O6	−1.8 (11)
C6—C5—C10—C9	−2.0 (9)	O5—C14—C15—O6	178.0 (6)
C8—C9—C10—C5	1.6 (9)	C14—O5—C12—C13	165.9 (10)
N1—N2—C22—C19	−178.9 (5)	C3—O2—C2—C1	176.1 (8)
C18—C19—C22—N2	173.6 (5)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C6—H6···O4ⁱ	0.93	2.57	3.483 (9)	169
C4—H4B···N1ⁱⁱ	0.97	2.69	3.618 (10)	161

Symmetry codes: (i) −x, y+1/2, −z−3/2; (ii) x−1, y, z.

Acknowledgements

Author contributions are as follows. Conceptualization, SD, SK, and KK; synthesis, SD and KK; writing (review and editing of the manuscript) SD, SK, FAA and KK; formal analysis, SD, KK and NB; crystal-structure determination, KK, SK and ND; validation, KK, ES and NB; project administration, KK, SD, ES and SK; molecular docking, FAA.

Funding information

Funding for this research was provided by Ondokuz Mayıs University under Project No. PYO·FEN.1906.19.001.

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