In the crystal of the anhydrous salt of levofloxacin with 4-methylbenzoic acid, C18H21FN3O4+·C8H7O2−, 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.
Keywords: crystal structure, levofloxacinium 4-methylbenzoate salt, Hirshfeld, X-ray diffraction, hydrogen-bonding interactions
Abstract
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.
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⋯O1iv | 0.97 | 2.58 | 3.268 (7) | 128 |
| C16—H16B⋯O2ii | 0.97 | 2.55 | 3.277 (7) | 131 |
| C18—H18C⋯F1v | 0.96 | 2.54 | 3.279 (8) | 134 |
| C28—H28B⋯O2vi | 0.96 | 2.60 | 3.481 (7) | 153 |
Symmetry codes: (i) 
; (ii) 
; (iii) 
; (iv) 
; (v) 
; (vi) 
.
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 dnorm 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 dnorm (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 ▸) |
| Tmin, Tmax | 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 |
| Δρmax, Δρmin (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) |
Supplementary Material
Crystal structure: contains datablock(s) I. DOI: 10.1107/S2056989025010047/ee2021sup1.cif
Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989025010047/ee2021Isup2.hkl
Supporting information file. DOI: 10.1107/S2056989025010047/ee2021Isup3.cml
CCDC reference: 2502089
Additional supporting information: crystallographic information; 3D view; checkCIF report
Acknowledgments
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.
supplementary crystallographic information
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 . Crystal data
| C18H21FN3O4+·C8H7O2− | Dx = 1.360 Mg m−3 |
| Mr = 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 |
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 . Data collection
| Bruker SMART APEXII CCD diffractometer | 2456 reflections with I > 2σ(I) |
| Radiation source: fine-focus sealed xray tube | Rint = 0.116 |
| ω scans | θmax = 27.2°, θmin = 1.8° |
| Absorption correction: analytical (SADABS; Krause et al., 2015) | h = −9→9 |
| Tmin = 0.575, Tmax = 0.746 | k = −16→14 |
| 17036 measured reflections | l = −33→33 |
| 5409 independent reflections |
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 . Refinement
| 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(Fo2) + (0.0526P)2] where P = (Fo2 + 2Fc2)/3 |
| wR(F2) = 0.177 | (Δ/σ)max = 0.001 |
| S = 1.00 | Δρmax = 0.23 e Å−3 |
| 5409 reflections | Δρmin = −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 |
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 . Special details
| 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. |
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 . Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)
| x | y | z | Uiso*/Ueq | ||
| 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* |
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 . Atomic displacement parameters (Å2)
| 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) |
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 . Geometric parameters (Å, º)
| 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) |
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 . Hydrogen-bond geometry (Å, º)
| 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···O1iv | 0.97 | 2.58 | 3.268 (7) | 128 |
| C16—H16B···O2ii | 0.97 | 2.55 | 3.277 (7) | 131 |
| C18—H18C···F1v | 0.96 | 2.54 | 3.279 (8) | 134 |
| C28—H28B···O2vi | 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.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Crystal structure: contains datablock(s) I. DOI: 10.1107/S2056989025010047/ee2021sup1.cif
Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989025010047/ee2021Isup2.hkl
Supporting information file. DOI: 10.1107/S2056989025010047/ee2021Isup3.cml
CCDC reference: 2502089
Additional supporting information: crystallographic information; 3D view; checkCIF report