Crystal structure and Hirshfeld surface analysis of anhydrous salt of levofloxacin and 4-methyl­benzoic acid

Patel, B.C.; Modi, K.M.; Reddy, J.P.

doi:10.1107/S2056989025010047

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ISSN: 2056-9890

Volume 81| Part 12| December 2025| Pages 1149-1152

https://doi.org/10.1107/S2056989025010047

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Crystal structure and Hirshfeld surface analysis of anhydrous salt of levofloxacin and 4-methylbenzoic acid

Bhumi C. Patel,^a Krunal M. Modi ^a and J. Prakasha Reddy ^a,^b ^*

^aDepartment of Chemistry, School of Sciences, Indrashil University, Rajpur, 382740, India, and ^bSchool of Applied Material Sciences, Central University of Gujarat, Vadodara, 391107, India
^*Correspondence e-mail: [email protected]

Edited by F. F. Ferreira, Universidade Federal do ABC, Brazil (Received 24 September 2025; accepted 11 November 2025; online 14 December 2025)

The anhydrous salt levofloxacinium 4-methylbenzoate, C₁₈H₂₁FN₃O₄⁺·C₈H₇O₂⁻, has been synthesized and its crystal structure determined. In the crystal, the levofloxacinium ions interact with the 4-methylbenzoate anion via N—H⁺⋯O⁻ and C—H⋯O hydrogen bonds, forming a tape-like supramolecular structure. Hirshfeld surface analysis and the calculated two-dimensional finger plots of the various atom–atom contacts involving both the ions are described.

Keywords: crystal structure; levofloxacinium 4-methylbenzoate salt; Hirshfeld; X-ray diffraction; hydrogen-bonding interactions.

CCDC reference: 2502089

1. Chemical context

Small organic molecules and peptides have been known for decades for their aesthetic supramolecular architectures (Prabhakaran et al., 2009 ; Upadhye et al., 2009 ) and various applications including in the pharmaceutical industry (Shah et al., 2023 ; Karmakar et al., 2025 ; Gellman, 1998 ). Fluoroquinolones belonging to a class of broad-spectrum antibiotics having advantageous pharmacokinetic properties and are used in the treatment of various bacterial infections. Levofloxacin, (levo isomer of oflaxacin), systematic name: S-(−)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyridine[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid, C₁₈H₂₀FN₃O₄, is a fluorinated third-generation fluoroquinolone antibiotic employed in the treatment of respiratory, urinary tract, cutaneous allergy and various other infections caused by Gram-positive and Gram-negative bacteria. A therapeutic review discussing the pharmacology, pharmacokinetics, in vitro activity, drug interactions, and adverse effects of levofloxacin has been published (Wimer et al., 1998 ) and the use of levofloxacin in the treatment of community-acquired pneumonia was described (Noreddin et al., 2010 ). A cohort analysis describing levofloxacin dosage to treat bone and joint infections was reported (Asseray et al., 2016 ). A literature review of the levofloxacin in veterinary medicine was published recently wherein levofloxacin MIC values of animal microbial isolates are summarized (Sitovs et al., 2021 ). A review on data summarizing the efficacy and the tolerability of levofloxacin in treating complicated urinary tract infections (UTIs) and pyelonephritis was described (Bientinesi et al., 2020 ), as well as a review of levofloxacin for the treatment of bacterial infections (Noel, 2009 ) has also been published. Recently, a retrospective observational study of the efficacy and safety of levofloxacin in children with severe infections was conducted (Junqi et al., 2024 ). Recently, levofloxacinium citrate salt hydrate (Nugrahani et al., 2024 ) was reported, the crystal structure of which features O—H⋯O, N—H⋯O and C—H⋯O interactions. Various solvates of levofloxacin and its citrate salt have also been reported (Nugrahani et al., 2022 ) wherein improvement in the antibiotic potency and an antibiotic–antioxidant combination for drug dosage development was reported. A study involving salts of levofloxacin with 2,6- and 3,5-dihydroxybenzoic acid showed increased stability and antibiotic potency improvement (Nugrahani et al., 2023 ). More recently, a drug–drug salt of levofloxacin flufenamic acid was reported along with its physicochemical properties, potency and anti-inflammation improvements that could be developed further into dosage formulations (Nugrahani et al., 2025 ).

The preparation of anhydrous forms of levofloxacin, salts or co-crystals (Freitas et al., 2018 ; Wei et al., 2019 ) continues to be challenging as these anhydrous forms readily convert into hemihydrate/hydrate forms (Singh et al., 2014 ). Continuing our research in the area of co-crystals (e.g. PrakashaReddy et al., 2004 ), we herein report the synthesis of a new anhydrous levofloxacinium:4-methylbenzoate salt, (I). We have determined its molecular and crystal structures and conducted a Hirshfeld surface analysis to examine the intermolecular interactions.

2. Structural commentary

Reaction between levofloxacin and 4-methylbenzoic acid yielded the title salt, (I), which crystallizes in the orthorhombic P2₁2₁2₁ space group with one ion pair in the asymmetric unit. The molecular structure of the salt along with the atom-labelling is shown in Fig. 1. The quinoline ring along with the other attached carboxyl and fluorine atoms in the levofloxacinium are essentially planar (r.m.s. deviation = 0.0659 Å), as observed in another salt hydrate reported in the literature (Golovnev et al., 2018 ). On the other hand, the carboxylate group in the 4-methylbenzoate is twisted notably from the planarity of methyl aromatic plane with a torsion angle of −18.1 (8)^o for the chain of O5—C21—C22—C27 atoms. An intramolecular O2—H2⋯O3 hydrogen bond is observed between the hydroxy O atom of the –COOH group and the adjacent quinoline oxygen atom, forming an S(6) ring motif, as seen in other salts/co-crystals of levofloxacin reported in the literature (Nugrahani et al., 2022).

Figure 1
The molecular structure of the levofloxacinium:4-methylbenzoate salt, showing the atom labelling and displacement ellipsoids drawn at the 30% probability level. Intramolecular hydrogen bonds are drawn as thick dashed lines while intermolecular hydrogen bonds are drawn as thin dashed lines.

3. Supramolecular features

In the crystal, intermolecular hydrogen-bonding interactions are observed. Levofloxacinium and 4-methylbenzoate ions are connected through the N5—H6⋯O8 interaction (Table 1). Further, a hydrogen atom of the methyl group of 4-methylbenzoate interacts with the hydroxy group –COOH of the levofloxacinium cation through the C28—H28B⋯O2 hydrogen bond (Desiraju, et al., 1999 ; Patel, et al., 2024 ), forming a tape-like supramolecular structure as shown in Fig. 2. In addition, a number of other C—H⋯O interactions (C16—H16B⋯O2, C12—H12C⋯O3, C11—H11⋯O6, C15—H15B⋯O1, C10—H10⋯O6, C13—H13A⋯O3) between levofloxacinium ions and both levofloxacinium and 4-methylbenzoate are observed in the crystal structure as shown in Fig. 3. The three-dimensional projection along the crystallographic b-axis is shown in Fig. 4.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯O3	0.82	1.76	2.522 (6)	155
N3—H3⋯O5	0.98	1.63	2.610 (6)	175
N3—H3⋯O6	0.98	2.51	3.125 (6)	121
C11—H11⋯O6ⁱ	0.98	2.28	3.147 (6)	147
C12—H12C⋯O3ⁱⁱ	0.96	2.52	3.308 (8)	139
C13—H13A⋯O3ⁱⁱⁱ	0.97	2.40	3.302 (8)	154
C14—H14B⋯F1	0.97	2.30	2.785 (6)	110
C15—H15B⋯O1^iv	0.97	2.58	3.268 (7)	128
C16—H16B⋯O2ⁱⁱ	0.97	2.55	3.277 (7)	131
C18—H18C⋯F1^v	0.96	2.54	3.279 (8)	134
C28—H28B⋯O2^vi	0.96	2.60	3.481 (7)	153
Symmetry codes: (i) ; (ii) $[x-{\script{1\over 2}}, -y+{\script{3\over 2}}, -z+1]$ ; (iii) $[x+{\script{1\over 2}}, -y+{\script{3\over 2}}, -z+1]$ ; (iv) ; (v) $[x-{\script{1\over 2}}, -y+{\script{1\over 2}}, -z+1]$ ; (vi) $[-x+{\script{3\over 2}}, -y+1, z+{\script{1\over 2}}]$ .

Figure 2
Formation of supramolecular tape-like structure through N—H⁺⋯O⁻ and C—H⋯O interactions in the crystal.

Figure 3
Various other C—H⋯O interactions observed in the crystal.

Figure 4
Three-dimensional packing viewed along the b-axis direction.

4. Hirshfeld surfaces and 2D fingerprint plots

A Hirshfeld surface analysis and corresponding fingerprint plots were generated using CrystalExplorer software (Spackman et al., 2021 ; Spackman & Jayatilaka, 2009 ) to further investigate and determine the contributions of the several intermolecular interactions in the crystal. The Hirshfeld surface mapped over d_norm with the corresponding two-dimensional fingerprint plots (McKinnon et al., 2007 ) for all intermolecular interactions and those delineated into specific contacts are shown in Fig. 5. The largest contribution comes from H⋯H contacts at 48.6% of the total, which is consistent with the significant hydrogen content of the molecule. The next most important contact is O⋯H/H⋯O at 24.5%, which primarily comes from the intramolecular O—H⋯O and intermolecular N—H⋯O as well as C—H⋯O interactions. The C⋯H/H⋯C interactions account for 12.1% while C⋯C contacts contribute 6.6%, followed by F⋯H/H⋯F contacts contributing 4.6%.

Figure 5
Hirshfeld surfaces of title compound mapped with d_norm (left image of each pair) and the corresponding two-dimensional fingerprint plots (right image of each pair) showing all contributions and then the major contributions of H⋯H followed by O⋯H/H⋯O, C⋯H/H⋯C, C⋯C and F⋯H/H⋯F contacts.

5. Synthesis and crystallization

Levofloxacin and 4-methylbenzoic acid were obtained from Aldrich, and HPLC grade methanol was used for reaction. Levofloxacin (100 mg, 0.277 mmol) was dissolved in methanol (10 ml) under constant stirring at 335 K for 40 min. Equimolar solution of 4-methylbenzoic acid (38 mg, 0.277 mmol) in methanol (10 ml) was added to the solution of levofloxacin and stirring was continued further for about 30 min at 335 K. The mixture was cooled to room temperature and the solution was filtered. X-ray quality single crystals of suitable dimension were obtained over a period of ten days by slow evaporation of the solvent.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. All hydrogen atoms were placed at idealized positions and refined using a riding model. The assignment of the absolute configuration is based on levofloxacin.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₈H₂₁FN₃O₄⁺·C₈H₇O₂⁻
M_r	497.51
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	120
a, b, c (Å)	7.1788 (10), 13.0274 (13), 25.979 (3)
V (Å³)	2429.6 (5)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.10
Crystal size (mm)	0.39 × 0.29 × 0.23

Data collection
Diffractometer	Bruker SMART APEXII CCD
Absorption correction	Analytical (SADABS; Krause et al., 2015 )
T_min, T_max	0.575, 0.746
No. of measured, independent and observed [I > 2σ(I)] reflections	17036, 5409, 2456
R_int	0.116
(sin θ/λ)_max (Å⁻¹)	0.644

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.060, 0.177, 1.00
No. of reflections	5409
No. of parameters	330
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.23, −0.17
Absolute structure	Flack x determined using 707 quotients [(I⁺)−(I⁻)]/[(I⁺)+(I⁻)] (Parsons et al., 2013 )
Absolute structure parameter	0.02 (10)
Computer programs: APEX2 (Bruker, 2005 ), SAINT (Bruker, 2017 ), SHELXT2018/2 (Sheldrick, 2015a ), SHELXL2019/3 (Sheldrick, 2015b ) and OLEX2 (Dolomanov et al., 2009 ).

Supporting information

CCDC reference: 2502089

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989025010047/ee2021sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989025010047/ee2021Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989025010047/ee2021Isup3.cml

checkCIF report

Computing details top

4-{11-Carboxy-7-fluoro-2-methyl-10-oxo-4-oxa-1-azatricyclo[7.3.1.0^{5,13}]trideca-5,7,9(13),11-tetraen-6-yl}-1-methylpiperazin-1-ium 4-methylbenzoate top

Crystal data top

C₁₈H₂₁FN₃O₄⁺·C₈H₇O₂⁻	D_x = 1.360 Mg m⁻³
M_r = 497.51	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P2₁2₁2₁	Cell parameters from 3952 reflections
a = 7.1788 (10) Å	θ = 2.5–27.5°
b = 13.0274 (13) Å	µ = 0.10 mm⁻¹
c = 25.979 (3) Å	T = 120 K
V = 2429.6 (5) Å³	Irregular, clear whiteish colourless
Z = 4	0.39 × 0.29 × 0.23 mm
F(000) = 1048

Data collection top

Bruker SMART APEXII CCD diffractometer	2456 reflections with I > 2σ(I)
Radiation source: fine-focus sealed xray tube	R_int = 0.116
ω scans	θ_max = 27.2°, θ_min = 1.8°
Absorption correction: analytical (SADABS; Krause et al., 2015)	h = −9→9
T_min = 0.575, T_max = 0.746	k = −16→14
17036 measured reflections	l = −33→33
5409 independent reflections

Refinement top

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F² > 2σ(F²)] = 0.060	w = 1/[σ²(F_o²) + (0.0526P)²] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.177	(Δ/σ)_max = 0.001
S = 1.00	Δρ_max = 0.23 e Å⁻³
5409 reflections	Δρ_min = −0.17 e Å⁻³
330 parameters	Absolute structure: Flack x determined using 707 quotients [(I⁺)-(I^-)]/[(I⁺)+(I^-)] (Parsons et al., 2013)
0 restraints	Absolute structure parameter: 0.02 (10)
Primary atom site location: dual

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.

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

	x	y	z	U_iso*/U_eq
F1	0.3846 (6)	0.4254 (2)	0.48601 (11)	0.0839 (13)
O4	0.4409 (7)	0.6279 (2)	0.63599 (12)	0.0654 (13)
O3	0.4055 (6)	0.7860 (3)	0.41864 (13)	0.0690 (12)
N1	0.4331 (7)	0.8049 (3)	0.57537 (14)	0.0507 (12)
O5	0.5049 (7)	0.1973 (2)	0.69163 (16)	0.0809 (14)
O2	0.4106 (8)	0.9794 (3)	0.41499 (15)	0.0817 (14)
H2	0.412608	0.918689	0.406726	0.123*
O6	0.5051 (8)	0.0488 (3)	0.65068 (18)	0.1007 (18)
N3	0.2677 (7)	0.2393 (3)	0.61849 (16)	0.0592 (14)
H3	0.351504	0.221625	0.646927	0.071*
N2	0.4162 (8)	0.4350 (3)	0.59214 (17)	0.0709 (16)
O1	0.4224 (8)	1.0696 (3)	0.48648 (15)	0.0909 (17)
C3	0.4150 (8)	0.7922 (4)	0.46730 (19)	0.0529 (14)
C2	0.4216 (8)	0.8873 (3)	0.49351 (19)	0.0510 (14)
C4	0.4170 (8)	0.7005 (3)	0.49911 (19)	0.0482 (13)
C7	0.4161 (9)	0.5228 (3)	0.5618 (2)	0.0530 (15)
C9	0.4225 (8)	0.7085 (3)	0.55283 (17)	0.0469 (13)
C8	0.4276 (8)	0.6204 (3)	0.58383 (17)	0.0505 (14)
C10	0.4327 (8)	0.8895 (4)	0.54619 (19)	0.0546 (15)
H10	0.440276	0.952924	0.562442	0.066*
C11	0.4308 (10)	0.8137 (3)	0.63186 (17)	0.0558 (16)
H11	0.502388	0.874645	0.641728	0.067*
C6	0.4047 (9)	0.5197 (4)	0.5082 (2)	0.0577 (16)
C16	0.1705 (9)	0.3364 (3)	0.6321 (2)	0.0596 (16)
H16A	0.101626	0.326800	0.663871	0.072*
H16B	0.082101	0.353582	0.605224	0.072*
C22	0.7367 (9)	0.0768 (4)	0.71312 (19)	0.0565 (16)
C5	0.4083 (9)	0.6029 (4)	0.4772 (2)	0.0574 (16)
H5	0.405122	0.595200	0.441643	0.069*
C1	0.4181 (10)	0.9871 (4)	0.4657 (2)	0.0651 (18)
C25	1.0649 (9)	0.0146 (4)	0.7643 (2)	0.0609 (16)
C23	0.7906 (10)	−0.0257 (4)	0.7157 (2)	0.0700 (19)
H23	0.717649	−0.075398	0.699742	0.084*
C21	0.5685 (10)	0.1086 (4)	0.6829 (2)	0.0678 (18)
C17	0.3068 (10)	0.4240 (4)	0.63871 (19)	0.0628 (17)
H17A	0.239637	0.487146	0.645588	0.075*
H17B	0.388308	0.410274	0.667678	0.075*
C13	0.5267 (10)	0.7203 (3)	0.65338 (19)	0.0639 (17)
H13A	0.656407	0.720735	0.642957	0.077*
H13B	0.522493	0.722761	0.690684	0.077*
C24	0.9502 (10)	−0.0553 (4)	0.7415 (2)	0.0657 (18)
H24	0.980162	−0.124614	0.743378	0.079*
C15	0.3828 (10)	0.2534 (4)	0.5714 (2)	0.073 (2)
H15A	0.302064	0.266210	0.542151	0.088*
H15B	0.452586	0.191077	0.564583	0.088*
C27	0.8484 (11)	0.1468 (4)	0.7376 (2)	0.074 (2)
H27	0.815831	0.215889	0.737288	0.089*
C26	1.0093 (12)	0.1159 (4)	0.7628 (2)	0.085 (2)
H26	1.081991	0.165116	0.779177	0.102*
C14	0.5154 (10)	0.3417 (4)	0.5778 (2)	0.076 (2)
H14A	0.606069	0.325097	0.604224	0.091*
H14B	0.581967	0.352980	0.545812	0.091*
C12	0.2334 (11)	0.8264 (4)	0.6508 (2)	0.080 (2)
H12A	0.178361	0.885510	0.634783	0.120*
H12B	0.233870	0.835415	0.687461	0.120*
H12C	0.162330	0.766401	0.642152	0.120*
C28	1.2434 (10)	−0.0176 (5)	0.7894 (2)	0.083 (2)
H28A	1.255020	−0.090935	0.787757	0.125*
H28B	1.243211	0.003861	0.824784	0.125*
H28C	1.346502	0.013623	0.771844	0.125*
C18	0.1332 (11)	0.1541 (4)	0.6121 (3)	0.086 (2)
H18A	0.071686	0.141200	0.644297	0.129*
H18B	0.198158	0.093334	0.601357	0.129*
H18C	0.042429	0.172378	0.586578	0.129*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.124 (4)	0.0551 (17)	0.072 (2)	−0.009 (2)	0.020 (2)	−0.0210 (15)
O4	0.098 (4)	0.0453 (17)	0.053 (2)	0.002 (2)	−0.007 (2)	−0.0014 (15)
O3	0.079 (3)	0.079 (2)	0.048 (2)	−0.001 (3)	0.003 (2)	0.0036 (18)
N1	0.060 (4)	0.044 (2)	0.049 (2)	0.000 (2)	−0.004 (2)	−0.0011 (17)
O5	0.096 (4)	0.050 (2)	0.097 (3)	0.015 (2)	−0.025 (3)	−0.0044 (19)
O2	0.102 (4)	0.077 (2)	0.066 (3)	−0.015 (3)	−0.006 (3)	0.020 (2)
O6	0.119 (5)	0.057 (2)	0.127 (4)	0.012 (2)	−0.065 (4)	−0.019 (2)
N3	0.068 (4)	0.044 (2)	0.066 (3)	0.001 (2)	−0.011 (3)	−0.0008 (19)
N2	0.097 (5)	0.042 (2)	0.074 (3)	0.013 (3)	0.031 (3)	0.005 (2)
O1	0.138 (5)	0.052 (2)	0.083 (3)	0.000 (3)	−0.006 (3)	0.009 (2)
C3	0.039 (4)	0.065 (3)	0.055 (3)	0.001 (3)	−0.001 (3)	0.003 (2)
C2	0.044 (4)	0.049 (3)	0.060 (3)	0.001 (3)	−0.003 (3)	0.004 (2)
C4	0.041 (4)	0.050 (3)	0.054 (3)	0.000 (3)	0.001 (3)	−0.002 (2)
C7	0.058 (4)	0.041 (2)	0.060 (3)	0.004 (3)	0.008 (3)	0.000 (2)
C9	0.050 (4)	0.043 (2)	0.048 (3)	0.002 (3)	−0.002 (3)	−0.002 (2)
C8	0.056 (4)	0.048 (2)	0.047 (3)	0.006 (3)	0.003 (3)	−0.001 (2)
C10	0.052 (4)	0.046 (3)	0.065 (3)	0.003 (3)	−0.008 (3)	0.002 (2)
C11	0.074 (5)	0.048 (3)	0.045 (3)	−0.003 (3)	−0.005 (3)	−0.006 (2)
C6	0.065 (5)	0.049 (3)	0.060 (4)	−0.001 (3)	0.008 (3)	−0.014 (3)
C16	0.064 (5)	0.049 (3)	0.066 (3)	0.010 (3)	−0.001 (3)	0.001 (3)
C22	0.064 (5)	0.047 (3)	0.058 (3)	0.001 (3)	−0.011 (3)	0.000 (2)
C5	0.060 (5)	0.059 (3)	0.053 (3)	0.002 (3)	0.003 (3)	−0.008 (2)
C1	0.066 (5)	0.063 (3)	0.066 (4)	−0.002 (4)	−0.006 (4)	0.015 (3)
C25	0.059 (5)	0.070 (3)	0.054 (3)	0.003 (3)	−0.007 (3)	−0.004 (3)
C23	0.082 (6)	0.048 (3)	0.080 (4)	0.000 (3)	−0.029 (4)	−0.007 (3)
C21	0.079 (6)	0.051 (3)	0.073 (4)	−0.008 (4)	−0.012 (4)	0.000 (3)
C17	0.084 (5)	0.047 (3)	0.057 (3)	0.005 (3)	0.004 (3)	0.001 (3)
C13	0.087 (5)	0.054 (3)	0.050 (3)	−0.001 (3)	−0.012 (3)	0.003 (2)
C24	0.078 (6)	0.055 (3)	0.064 (3)	0.006 (3)	−0.002 (4)	−0.004 (3)
C15	0.093 (6)	0.052 (3)	0.076 (4)	0.009 (3)	0.010 (4)	−0.008 (3)
C27	0.090 (6)	0.051 (3)	0.083 (4)	0.002 (4)	−0.018 (4)	−0.010 (3)
C26	0.091 (6)	0.063 (3)	0.102 (5)	−0.004 (4)	−0.029 (5)	−0.015 (3)
C14	0.091 (6)	0.045 (3)	0.092 (4)	0.010 (3)	0.025 (4)	−0.002 (3)
C12	0.100 (7)	0.081 (4)	0.060 (4)	0.014 (4)	0.011 (4)	−0.004 (3)
C28	0.069 (6)	0.097 (4)	0.083 (4)	0.009 (4)	−0.019 (4)	−0.011 (3)
C18	0.089 (6)	0.063 (3)	0.108 (5)	−0.015 (4)	−0.019 (4)	−0.010 (3)

Geometric parameters (Å, º) top

F1—C6	1.365 (5)	C16—H16B	0.9700
O4—C8	1.362 (5)	C16—C17	1.512 (8)
O4—C13	1.426 (6)	C22—C23	1.392 (7)
O3—C3	1.269 (6)	C22—C21	1.498 (8)
N1—C9	1.388 (6)	C22—C27	1.371 (8)
N1—C10	1.337 (6)	C5—H5	0.9300
N1—C11	1.472 (6)	C25—C24	1.363 (7)
O5—C21	1.264 (6)	C25—C26	1.379 (8)
O2—H2	0.8200	C25—C28	1.498 (8)
O2—C1	1.323 (6)	C23—H23	0.9300
O6—C21	1.231 (6)	C23—C24	1.382 (9)
N3—H3	0.9800	C17—H17A	0.9700
N3—C16	1.488 (6)	C17—H17B	0.9700
N3—C15	1.488 (7)	C13—H13A	0.9700
N3—C18	1.481 (7)	C13—H13B	0.9700
N2—C7	1.389 (6)	C24—H24	0.9300
N2—C17	1.449 (7)	C15—H15A	0.9700
N2—C14	1.458 (6)	C15—H15B	0.9700
O1—C1	1.202 (6)	C15—C14	1.503 (8)
C3—C2	1.415 (6)	C27—H27	0.9300
C3—C4	1.453 (6)	C27—C26	1.387 (9)
C2—C10	1.371 (6)	C26—H26	0.9300
C2—C1	1.487 (7)	C14—H14A	0.9700
C4—C9	1.400 (7)	C14—H14B	0.9700
C4—C5	1.394 (6)	C12—H12A	0.9600
C7—C8	1.396 (6)	C12—H12B	0.9600
C7—C6	1.396 (7)	C12—H12C	0.9600
C9—C8	1.402 (6)	C28—H28A	0.9600
C10—H10	0.9300	C28—H28B	0.9600
C11—H11	0.9800	C28—H28C	0.9600
C11—C13	1.505 (7)	C18—H18A	0.9600
C11—C12	1.509 (9)	C18—H18B	0.9600
C6—C5	1.350 (7)	C18—H18C	0.9600
C16—H16A	0.9700

C8—O4—C13	114.0 (4)	C24—C25—C28	121.2 (5)
C9—N1—C11	119.3 (4)	C26—C25—C28	121.9 (6)
C10—N1—C9	120.4 (4)	C22—C23—H23	119.3
C10—N1—C11	120.1 (4)	C24—C23—C22	121.4 (5)
C1—O2—H2	109.5	C24—C23—H23	119.3
C16—N3—H3	108.0	O5—C21—C22	116.8 (5)
C15—N3—H3	108.0	O6—C21—O5	124.5 (6)
C15—N3—C16	110.6 (4)	O6—C21—C22	118.7 (5)
C18—N3—H3	108.0	N2—C17—C16	109.3 (4)
C18—N3—C16	111.0 (5)	N2—C17—H17A	109.8
C18—N3—C15	111.3 (4)	N2—C17—H17B	109.8
C7—N2—C17	123.7 (4)	C16—C17—H17A	109.8
C7—N2—C14	122.8 (4)	C16—C17—H17B	109.8
C17—N2—C14	113.3 (4)	H17A—C17—H17B	108.3
O3—C3—C2	122.5 (4)	O4—C13—C11	111.5 (4)
O3—C3—C4	121.0 (4)	O4—C13—H13A	109.3
C2—C3—C4	116.5 (4)	O4—C13—H13B	109.3
C3—C2—C1	122.1 (5)	C11—C13—H13A	109.3
C10—C2—C3	120.0 (4)	C11—C13—H13B	109.3
C10—C2—C1	117.9 (4)	H13A—C13—H13B	108.0
C9—C4—C3	120.4 (4)	C25—C24—C23	121.7 (5)
C5—C4—C3	121.2 (5)	C25—C24—H24	119.1
C5—C4—C9	118.4 (4)	C23—C24—H24	119.1
N2—C7—C8	121.1 (4)	N3—C15—H15A	109.5
N2—C7—C6	122.9 (4)	N3—C15—H15B	109.5
C6—C7—C8	116.0 (4)	N3—C15—C14	110.8 (4)
N1—C9—C4	119.3 (4)	H15A—C15—H15B	108.1
N1—C9—C8	119.8 (4)	C14—C15—H15A	109.5
C4—C9—C8	120.8 (4)	C14—C15—H15B	109.5
O4—C8—C7	118.5 (4)	C22—C27—H27	119.6
O4—C8—C9	121.0 (4)	C22—C27—C26	120.8 (5)
C7—C8—C9	120.5 (4)	C26—C27—H27	119.6
N1—C10—C2	123.3 (4)	C25—C26—C27	122.2 (6)
N1—C10—H10	118.3	C25—C26—H26	118.9
C2—C10—H10	118.3	C27—C26—H26	118.9
N1—C11—H11	108.5	N2—C14—C15	110.9 (5)
N1—C11—C13	107.6 (4)	N2—C14—H14A	109.5
N1—C11—C12	110.1 (5)	N2—C14—H14B	109.5
C13—C11—H11	108.5	C15—C14—H14A	109.5
C13—C11—C12	113.4 (5)	C15—C14—H14B	109.5
C12—C11—H11	108.5	H14A—C14—H14B	108.0
F1—C6—C7	116.9 (4)	C11—C12—H12A	109.5
C5—C6—F1	118.3 (4)	C11—C12—H12B	109.5
C5—C6—C7	124.8 (4)	C11—C12—H12C	109.5
N3—C16—H16A	109.3	H12A—C12—H12B	109.5
N3—C16—H16B	109.3	H12A—C12—H12C	109.5
N3—C16—C17	111.4 (5)	H12B—C12—H12C	109.5
H16A—C16—H16B	108.0	C25—C28—H28A	109.5
C17—C16—H16A	109.3	C25—C28—H28B	109.5
C17—C16—H16B	109.3	C25—C28—H28C	109.5
C23—C22—C21	121.0 (5)	H28A—C28—H28B	109.5
C27—C22—C23	117.0 (6)	H28A—C28—H28C	109.5
C27—C22—C21	122.0 (5)	H28B—C28—H28C	109.5
C4—C5—H5	120.3	N3—C18—H18A	109.5
C6—C5—C4	119.3 (5)	N3—C18—H18B	109.5
C6—C5—H5	120.3	N3—C18—H18C	109.5
O2—C1—C2	114.7 (5)	H18A—C18—H18B	109.5
O1—C1—O2	121.0 (5)	H18A—C18—H18C	109.5
O1—C1—C2	124.3 (5)	H18B—C18—H18C	109.5
C24—C25—C26	116.8 (6)

F1—C6—C5—C4	176.0 (5)	C10—N1—C11—C12	84.3 (6)
O3—C3—C2—C10	−179.7 (6)	C10—C2—C1—O2	178.9 (6)
O3—C3—C2—C1	0.0 (10)	C10—C2—C1—O1	−0.8 (10)
O3—C3—C4—C9	−178.3 (6)	C11—N1—C9—C4	177.4 (5)
O3—C3—C4—C5	−0.1 (9)	C11—N1—C9—C8	−6.0 (9)
N1—C9—C8—O4	0.7 (9)	C11—N1—C10—C2	−175.3 (6)
N1—C9—C8—C7	179.7 (6)	C6—C7—C8—O4	−179.4 (5)
N1—C11—C13—O4	−56.6 (6)	C6—C7—C8—C9	1.6 (9)
N3—C16—C17—N2	56.2 (6)	C16—N3—C15—C14	54.8 (6)
N3—C15—C14—N2	−54.6 (6)	C22—C23—C24—C25	−1.9 (10)
N2—C7—C8—O4	0.7 (9)	C22—C27—C26—C25	0.3 (10)
N2—C7—C8—C9	−178.3 (6)	C5—C4—C9—N1	179.4 (5)
N2—C7—C6—F1	2.9 (10)	C5—C4—C9—C8	2.8 (9)
N2—C7—C6—C5	−178.5 (6)	C1—C2—C10—N1	178.6 (6)
C3—C2—C10—N1	−1.7 (10)	C23—C22—C21—O5	164.6 (6)
C3—C2—C1—O2	−0.8 (9)	C23—C22—C21—O6	−17.5 (9)
C3—C2—C1—O1	179.6 (7)	C23—C22—C27—C26	1.2 (9)
C3—C4—C9—N1	−2.4 (9)	C21—C22—C23—C24	177.0 (6)
C3—C4—C9—C8	−179.0 (5)	C21—C22—C27—C26	−176.2 (6)
C3—C4—C5—C6	−177.9 (6)	C17—N2—C7—C8	44.6 (9)
C2—C3—C4—C9	0.9 (9)	C17—N2—C7—C6	−135.3 (6)
C2—C3—C4—C5	179.1 (6)	C17—N2—C14—C15	57.0 (7)
C4—C3—C2—C10	1.1 (9)	C13—O4—C8—C7	155.4 (5)
C4—C3—C2—C1	−179.2 (6)	C13—O4—C8—C9	−25.6 (8)
C4—C9—C8—O4	177.2 (5)	C24—C25—C26—C27	−2.5 (10)
C4—C9—C8—C7	−3.8 (9)	C15—N3—C16—C17	−56.0 (6)
C7—N2—C17—C16	118.4 (6)	C27—C22—C23—C24	−0.4 (9)
C7—N2—C14—C15	−118.4 (6)	C27—C22—C21—O5	−18.1 (8)
C7—C6—C5—C4	−2.6 (10)	C27—C22—C21—O6	159.9 (6)
C9—N1—C10—C2	0.2 (9)	C26—C25—C24—C23	3.3 (9)
C9—N1—C11—C13	32.8 (8)	C14—N2—C7—C8	−140.5 (6)
C9—N1—C11—C12	−91.2 (6)	C14—N2—C7—C6	39.6 (10)
C9—C4—C5—C6	0.3 (9)	C14—N2—C17—C16	−57.0 (7)
C8—O4—C13—C11	54.5 (6)	C12—C11—C13—O4	65.4 (6)
C8—C7—C6—F1	−177.0 (5)	C28—C25—C24—C23	−176.2 (6)
C8—C7—C6—C5	1.6 (10)	C28—C25—C26—C27	177.0 (6)
C10—N1—C9—C4	1.9 (9)	C18—N3—C16—C17	180.0 (4)
C10—N1—C9—C8	178.5 (5)	C18—N3—C15—C14	178.6 (5)
C10—N1—C11—C13	−151.6 (5)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O3	0.82	1.76	2.522 (6)	155
N3—H3···O5	0.98	1.63	2.610 (6)	175
N3—H3···O6	0.98	2.51	3.125 (6)	121
C11—H11···O6ⁱ	0.98	2.28	3.147 (6)	147
C12—H12C···O3ⁱⁱ	0.96	2.52	3.308 (8)	139
C13—H13A···O3ⁱⁱⁱ	0.97	2.40	3.302 (8)	154
C14—H14B···F1	0.97	2.30	2.785 (6)	110
C15—H15B···O1^iv	0.97	2.58	3.268 (7)	128
C16—H16B···O2ⁱⁱ	0.97	2.55	3.277 (7)	131
C18—H18C···F1^v	0.96	2.54	3.279 (8)	134
C28—H28B···O2^vi	0.96	2.60	3.481 (7)	153

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

Acknowledgements

The authors are grateful to the Indrashil University and Central University of Gujarat, India, for research facilities. One of the authors (BCP) is indebted to the Knowledge Consortium of Gujarat (KCG), Department of Education, Government of Gujarat, India for a SHODH-Scheme fellowship. We thank an anonymous referee for constructive comments and suggestions.

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