Norfloxacinium nitrate

The components of the title molecular salt are linked by N—H⋯O hydrogen bonds and aromatic π–π stacking interactions.


Structure description
Norfloxacin (NF, C 16 H 18 N 3 O 3 F) is a synthetic fluoroquinolone antibiotic that has been used to treat a wide variety of bacterial infections since its introduction in the 1980s.It is effective against both Gram-positive and Gram-negative bacteria, and it has been shown to be particularly useful in the treatment of urinary tract infections, respiratory tract infections, and skin and soft tissue infections.Norfloxacin works by inhibiting the bacterial enzyme DNA gyrase, which is essential for DNA replication and transcription (Goldstein et al., 1987;Mazuel, 1991;Chongcharoen et al., 2008;Marc et al., 2019;Spencer et al., 2023).As part of our studies in this area we now describe the synthesis and structure of the title molecular salt, C 16 H 19 N 3 O 3 F + •NO 3 À , (I), arising from the reaction of norfloxacin and nitric acid in aqueous solution.
Compound (I) crystallizes in the monoclinic space group P2 1 /n, with one cation and one anion in the asymmetric unit (Fig. 1).The N3 nitrogen atom of the piperazine ring is observed to be protonated.In neutral NF, this nitrogen atom is protonated by a hydrogen atom from the carboxylic acid moiety, resulting in a zwitterionic species (e.g., Gunnam & Nangia, 2023).However, in the crystal structure of (I), the hydrogen atom remains attached to the carboxylic acid fragment.This is evident from the significant difference (0.117 A ˚) in the lengths of the C10-O1 and C10-O2 bonds [1.325 (2) and 1.208 (2) A ˚, respectively].In a delocalized carboxylic acid moiety, the C-O bond lengths are typically very similar, with a difference of only 0.006 A ˚ (Razzoqova et al., 2022).The atoms of the carboxyl moiety (C10, O1, and O2) and the quinoline moiety lie essentially in a plane, with maximum deviations from the mean plane of 0.029 (2) A ˚for O2 and 0.030 (2) A ˚for O1.The dihedral angle between the carboxyl and quinoline planes is 1.90 (19) � .The nitrogen atom (N2) attached to the quinoline moiety is close to planar, as evidenced by the sum of bond angles around it being 356.5 � .In contrast, the protonated nitrogen atom (N3) adopts a tetrahedral geometry.The piperazine ring exhibits a chair conformation.The ethyl substituent attached to N1 lies essentially in the plane of the quinoline moiety, as indicated by the C1-N1-C11-C12 torsion angle of 0.7 (2) � .The C5-F1 bond length of 1.3506 (18) A ˚is in good agreement with the mean value reported for 128 structures containing the NF moiety [e.g., 1.350 (2) A ˚reported by Sultana et al., 2023].Atom F1 accepts an intramolecular hydrogen bond from H13B (C13-H13B� � �F1; Table 1), forming an S(6) ring.Another intramolecular hydrogen bond is observed between H1 and O3 (O1-H1� � �O3), also forming a six-membered ring.Additionally, a weak hydrogen bond is present between H1A and O2 (C1-H1A� � �O2), forming a five-membered ring.
In the extended structure of (I), the norflaxacinium cation forms a hydrogen bond with the nitrate anion via its NH group (N3-H3B� � �O4).The nitrate anion, in turn, accepts a hydrogen bond from the NH group (N3-H3A� � �O6) of an adjacent NF cation related by the symmetry operation 1 + x, y, z (Table 1).These hydrogen bonds generate an infinite chain of alternating cations and anions propagating along the [100] direction (Fig. 2).This packing arrangement is repeated on the opposite side of the chain.As a result, strong �-� stacking interactions are formed between layers of NF cations facing each other (Fig. 3).The �-� stacking interactions are observed between the original NF cation and its symmetry-related counterparts located at À x, 1 À y, 1 À z and 1 À x, 1 À y, 1 À z.These interactions are highlighted by the short centroidcentroid distances: ånd Cg1-Cg1 is 3.4403 (7) A ˚, and Cg1-Cg3(1 À x, 1 À y, 1 À z) is 3.5919 (8) A ˚and Cg1-Cg1 is 3.4862 (7) A ˚.These distances are notably shorter than the centroid-centroid contacts reported by Ibukun et al. (2023) and Shaikh et al. (2024).The angle between the mean planes of the quinoline moieties is zero by symmetry.These stacking interactions also contribute to the packing of molecules along the [100] direction.
data reports

Figure 2
A fragment of a [100] chain in the extended structure of (I), with hydrogen bonds shown as dashed lines.
Figure 3 A view of the �-� stacking interaction along the a-axis direction.

Figure 1
The molecular structure of (I).Displacement ellipsoids are shown at the 50% probability level and hydrogen bonds are indicated by dashed lines.

Synthesis and crystallization
31.9 mg (0.1 mmol) of NF was dissolved in 5 ml of a 0.02 M nitric acid solution.The resulting clear solution was stirred at room temperature for 30 minutes.The solution was then transferred to a vial with small holes in the lid to allow for evaporation.After about a week, needle-like single crystals of the title salt suitable for data collection were obtained.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2.
data reports

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.

Table 2
Experimental details.