Pharmaceutical organic salt: Disordered crystal structure of levofloxacin with γ-resorcylic acid European Journal of Chemistry 12 (3) (2021) 323-328 European Journal of Chemistry ISSN 2153-2249 (Print) / ISSN 2153-2257 (Online) – Copyright © 2021 The Authors – Atlanta Publishing House LLC – Printed in the USA. This work is published and licensed by Atlanta Publishing House LLC – CC BY NC – Some Rights Reserved. https://dx.doi.org/10.5155/eurjchem.12.3.323-328.2134 European Journal of Chemistry View Journal Online View Article Online Pharmaceutical organic salt: Disordered crystal structure of levofloxacin with γ-resorcylic acid Syed Muddassir Ali Mashhadi 1,2,*, Muhammad Nawaz Tahir 3, David Apperley 4, Moazzam Hussain Bhatti 1, Muhammad Ashfaq 3,5 and Uzma Yunus 1,* 1 Department of Chemistry, Allama Iqbal Open University, Islamabad, 44310, Pakistan muddassir_bakie@yahoo.com (S.M.A.M.), moazzamhussain_b@yahoo.com (M.H.B.), uzma_yunus@yahoo.com (U.Y.) 2 Department of Chemistry, University of Agriculture Faisalabad (Depalpur Okara Campus), Okara, 56130, Pakistan 3 Department of Physics, University of Sargodha, Sargodha, 40100, Pakistan dmntahir_uos@yahoo.com (M.N.T.), muhammadashfaq1400@gmail.com (M.A.) 4 Department of Chemistry, Durham University, Stockton Road, Durham, DH1 3LE, United Kingdom d.c.apperley@durham.ac.uk (D.A.) 5 Department of Physics, University of Mianwali, Mianwali, 42200, Pakistan * Corresponding author at: Department of Chemistry, Allama Iqbal Open University, Islamabad, 44310, Pakistan. e-mail: muddassir_bakie@yahoo.com (S.M.A. Mashhadi); uzma_yunus@yahoo.com (U. Yunus). 10.5155/eurjchem.12.3.323-328.2134 Received: 06 July 2021 Received in revised form: 02 August 2021 Accepted: 08 August 2021 Published online: 30 September 2021 Printed: 30 September 2021 This study reports an organic salt prepared from an antibacterial drug, levofloxacin and antioxidant γ-resorcylic acid. A simple preparation method leads to a crystal with disordered structure. The idea is to prepare an organic salt comprising of pharmaceutically acceptable acidic and basic components. The salt is characterised by IR, solid state NMR, and single crystal XRD. Crystal data for C25H26N3O8F: triclinic, space group P-1 (no. 2), a = 7.0037(8) Å, b = 12.764(3) Å, c = 13.909(3) Å, α = 104.821(4)°, β = 92.039(4)°, γ = 95.334(4)°, V = 1194.6(4) Å3, Z = 2, T = 296(2) K, μ(MoKα) = 0.113 mm-1, Dcalc = 1.433 g/cm3, 16879 reflections measured (5.048° ≤ 2Θ ≤ 54.186°), 5139 unique (Rint = 0.0663, Rsigma = 0.0975) which were used in all calculations. The final R1 was 0.1121 (I>2σ(I)) and wR2 was 0.2505 (all data). SC-XRD analysis shows that the crystal packing is stabilized by strong H-bonding of type N-H···O and comparatively weak interactions of type C-H···O, C-H···π and off-set π···π stacking. SC-XRD SS-NMR Organic salt Levofloxacin γ-Resorcylic acid Disordered crystal structure Cite this: Eur. J. Chem. 2021, 12(3), 323-328 Journal website: www.eurjchem.com 1. Introduction Multicomponent crystals [1], such as salts, cocrystals [2-5], and solvates / hydrates, play a key role in the design of novel solid forms, especially in the pharmaceutical arena. Solid forms display exclusive physicochemical properties influencing key features of the formulated API like bioavailability, stability, flowability and manufacturability [6]. About 50% of marketed drugs are in salt form consisting stoichiometric ratio of anion and cation keeping in view of the higher bioavailability associated with them [7]. Generally, for complementary ions a pKa difference of ≥3 is expected for formation of salts [8], however it is not a universal truth applicable to salt formation. Improvement of dissolution, stability, hygroscopicity, and solubility profile can be achieved, which makes salt selection a multi-dimensional approach. Pharmaceutical organic salt [9,10] is an important solid-state form of drugs having impact during drug development process. Levofloxacin (LEV), the levo isomer of ofloxacin, is a third generation fluoroquinolone that is used as a broad-spectrum antibiotic for various Gram-positive and Gram-negative organisms [11] and some other pathogens such as Mycoplasma, Chlamydia, Legionella, and Myobacteria spp. [12] are also used for the treatment of chronic bronchitis as well as urinary tract, kidney and skin infections [13] in patients with severe pneumonia and legionnaires disease levofloxacin exerted superior activity [13]. LEV is slightly water soluble having unpleasant taste and keeping in view of its lower solubility it is administered as a hydrochloride salt. It is absorbed from the gastrointestinal tract and the peak plasma concentration is reached in 1 to 2 hours after oral intake. Pharmacokinetically, LEV shows high bioavailability, low protein binding (30-40%), high tissue concentrations, and elimination via the kidneys with negligible liver metabolism. ABSTRACT RESEARCH ARTICLE KEYWORDS https://dx.doi.org/10.5155/eurjchem.12.3.323-328.2134 https://www.eurjchem.com/ https://dx.doi.org/10.5155/eurjchem.12.3.323-328.2134 mailto:muddassir_bakie@yahoo.com mailto:moazzamhussain_b@yahoo.com mailto:uzma_yunus@yahoo.com mailto:dmntahir_uos@yahoo.com mailto:muhammadashfaq1400@gmail.com mailto:d.c.apperley@durham.ac.uk mailto:muddassir_bakie@yahoo.com mailto:uzma_yunus@yahoo.com http://www.eurjchem.com/ https://crossmark.crossref.org/dialog/?doi=10.5155/eurjchem.12.3.323-328.2134&domain=pdf&date_stamp=2021-09-30 324 Mashhadi et al. / European Journal of Chemistry 12 (3) (2021) 323-328 2021 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.12.3.323-328.2134 N O N HO O O F N LEV N O N HO O O F N H O O HO OH CH2 HO O HO OH 26DHBA LEV-26DHBA Ethanol+ Scheme 1. Preparation of LEV-26DHBA. γ-Resorcylic acid, also called 2,6-dihydroxybenzoic acid (26DHBA), is one of the strongest carboxylic acids [14] that has intramolecular hydrogen bonding. It is secondary metabolite of salicylic acid which is hydrolysed by liver enzymes. As 26DHBA is not a hazardous substance or generally regarded as safe (GRAS) compound according to regulations and its acidity makes it ideal for organic salt preparation. In this study we report development (Scheme 1) and structure elucidation of an organic salt of LEV with pKa = 6.2 and 26DHBA having pKa = 1.3. prepared organic salt 4-(6- carboxy-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-[1,4]oxazino [2,3,4-ij]quinolin -10-yl)-1-methylpiperazin-1-ium 2,6-dihyd- roxybenzoate (LEV-26DHBA) comprises of an antibacterial and an antioxidant GRAS component with the disordered crystal structure. 2. Experimental 2.1. Instrumentation The Infrared spectra were recorded on Varian 640-IR spectrophotometer in ATR mode. Solid-state 13C NMR spectra were recorded on a Bruker Avance III HD spectrometer with a 13C resonant frequency of 125.7 MHz at a magnetic field strength of 11.7 T. 100 mg of crystalline sample was packed into a 4-mm rotor made up of zirconia equipped with a Kel-F cap. Spectral acquisition was done by the cross-polarization magic angle spinning (CP-MAS) pulse sequence at a spinning rate of 10.00 kHz. Magic angle calibration was done using KBr. Spectra were obtained using a relaxation delay of 4 seconds for LEV and LEV-26DHBA, while the same was 300 seconds for 26DHBA. Number of scans were 12800 for LEV, 1480 for LEV-26DHBA and 24 for 26DHBA. Data sets were Fourier transformed with a 5 Hz line broadening factor and phase corrected to produce a frequency domain spectrum. The chemical shifts were referenced indirectly to neat tetramethyl silane by setting the high frequency signal of adamantane to 38.5 ppm. Single crystal X-ray data was collected using a Bruker Kappa APEX II CCD diffractometer equipped with a graphite monochromator at 296 K. A fine focus of MoKα tube was used. Data were collected using APEX2 software, SAINT, for indexing the reflections and determining the unit cell parameters. The structure was solved by direct methods using SHELXS-97 software and refined by full-matrix least square calculations using SHELXL-2018/3 software. Crystallographic data for the structure has been deposited with the Cambridge Crystallographic Data Centre with CCDC deposition number 1976923. PLATON and Mercury 4.2 are utilized for the graphical representation of SC-XRD results. 2.2. Preparation of LEV-26DHBA Isoniazid was received as a gift and other chemicals were purchased from Merck and were used as received from the supplier without any further purification. LEV and 26DHBA were separately dissolved in ethanol by sonication for 3 minutes, both equimolar (1 millimolar) solutions were mixed after heating at 45 °C. A white solid was formed when the two solutions were mixed (nearly all of the reacting material gave the product). Solid-state NMR suggested the product formation. Good crystals for the single-crystal XRD experiment were grown by dissolving the coformers in large amounts of solvent which were mixed and placed for slow evaporation of the solvent. White crystals were formed after seven days. 3. Result and discussion 3.1. Characterization The IR spectra of LEV-26DHB revealed that the characteristic aromatic ring peaks, cyclic ketone, and amine groups are retained in the compound. The O-H stretch peak is present at 3065 cm-1. Carboxylate anion (–COO−) formation due to salt formation which shows a single stretch at 1232 cm-1 [15]. Stretch at 1089 cm-1 is due to the presence of fluorine. An asymmetric stretch at 1619 cm-1 and symmetric stretch at 1450 cm-1 are identified for amine salts. The ammine stretch is present at 3479 cm-1. The peak at 1713 cm-1 is due to the stretching of the carbonyl group. Figure 1 shows the carbon-13 solid-state NMR spectra of the product and the coformers. The spectrum of the product is clearly distinguishable from the starting materials. There is no evidence for a significant contribution to the product spectrum from either of the starting materials (although it should be noted that it would be difficult to detect the 26DHBA component under the experimental conditions used to obtain the spectrum from the product). Several resonances between δ 120 and 140 ppm in the spectrum of the product appear in pairs. These are most likely to be associated with the LEV component of the product. This is consistent with the disorder over the two sites detected in the XRD measurement. 3.2. Single crystal structure In LEV-26DHBA (Figure 2, Table 1) some parts of both cation and anion are disordered over two sets of sites with occupancy ratio of 0.541(12):0.459(12). Some important bond lengths and bond angles are given in Tables 2 and 3. In the cation, the 4-(6-carboxy-9-fluoro-3-methyl-7-oxo-2,3-dihyd ro-7H-[1, 4] oxazino[2,3,4-ij]quinolin-10-yl) part is disordered, A (C1-C10/C11A/C12A/C13A/N1/O1-O4/F1) and B (C1-C10/ C11B/C12B/C13B/N1/O1-O4/F1) are roughly planar with RMS deviations of 0.1412 and 0.1396 Å, respectively. The piperazine group is in the chair conformation with the basal plane C (C14-C17) [RMS deviation 0.0063 Å] and the apical atoms N2 and N3 at a distance of -0.664(9) and 0.630(9) Å, respectively. This major difference is due to the attached methyl group at N3 and the hydrogen coming from the carboxyl group of 26DHBA. The dihedral angle between A/B, A/C, and B/C is 1.668(17), 56.62(22) and 57.92(22)°, respectively. In the anion 2,6-dihyd- roxybenzoate, the dihydroxybenzene is disordered with major and minor parts D (C20A-C25A/O7A/O8A) [RMS deviation 0.0635 Å] and E (C20B-C25B/O7B/O8B) [RMS deviation 0.0814 Å]. Mashhadi et al. / European Journal of Chemistry 12 (3) (2021) 323-328 325 2021 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.12.3.323-328.2134 Table 1. Crystal data and structure refinement for LEV-26DHBA PUB. Empirical formula C25H26N3O8F Formula weight 515.49 Temperature (K) 296(2) Crystal system Triclinic Space group P-1 a, (Å) 7.0037(8) b, (Å) 12.764(3) c, (Å) 13.909(3) α (°) 104.821(4) β (°) 92.039(4) γ (°) 95.334(4) Volume (Å3) 1194.6(4) Z 2 ρcalc (g/cm3) 1.433 μ (mm-1) 0.113 F(000) 540.0 Crystal size (mm3) 0.40 × 0.22 × 0.18 Radiation MoKα (λ = 0.71073) 2Θ range for data collection (°) 5.048 to 54.186 Index ranges -8 ≤ h ≤ 7, -16 ≤ k ≤ 16, -17 ≤ l ≤ 17 Reflections collected 16879 Independent reflections 5139 [Rint = 0.0663, Rsigma = 0.0975] Data/restraints/parameters 5139/14/303 Goodness-of-fit on F2 1.039 Final R indexes [I≥2σ (I)] R1 = 0.1121, wR2 = 0.2189 Final R indexes [all data] R1 = 0.2040, wR2 = 0.2505 Largest diff. peak/hole (e Å-3) 0.35/-0.39 CCDC number 1976923 Table 2. Bond lengths for LEV-26DHBA. Atom Atom Length (Å) Atom Atom Length (Å) F1 C8 1.362(6) C11A C12A 1.506(15) O1 C1 1.330(7) C12A C13A 1.512(15) O2 C1 1.199(7) C11B C12B 1.485(17) O3 C3 1.270(6) C12B C13B 1.516(17) O4 C11A 1.365(12) C14 C15 1.503(8) O4 C10 1.368(6) C16 C17 1.500(8) O4 C11B 1.408(13) O5 C19 1.286(9) N1 C6 1.340(7) O6 C19 1.246(9) N1 C5 1.404(7) C19 C20B 1.441(12) N1 C12B 1.494(13) C19 C20A 1.522(11) N1 C12A 1.501(12) O7A C21A 1.352(12) N2 C9 1.393(7) O8A C25A 1.318(11) N2 C17 1.445(7) C20A C21A 1.3900 N2 C14 1.458(7) C20A C25A 1.3900 N3 C15 1.481(8) C21A C22A 1.3900 N3 C16 1.487(7) C22A C23A 1.3900 N3 C18 1.488(7) C23A C24A 1.3900 C1 C2 1.485(8) C24A C25A 1.3900 C2 C6 1.350(8) O7B C21B 1.347(13) C2 C3 1.434(8) O8B C25B 1.384(13) C3 C4 1.442(7) C20B C21B 1.3900 C4 C5 1.405(7) C20B C25B 1.3900 C4 C7 1.416(8) C21B C22B 1.3900 C5 C10 1.397(7) C22B C23B 1.3900 C7 C8 1.337(8) C23B C24B 1.3900 C8 C9 1.410(8) C24B C25B 1.3900 C9 C10 1.399(8) Figure 1. 13C solid state NMR spectrum of LEV-26DHBA. 326 Mashhadi et al. / European Journal of Chemistry 12 (3) (2021) 323-328 2021 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.12.3.323-328.2134 Table 3. Bond Angles for LEV-26DHBA. Atom Atom Atom Angle (°) Atom Atom Atom Angle (°) C11A O4 C10 115.7(8) N1 C12A C11A 107.8(11) C10 O4 C11B 114.9(8) N1 C12A C13A 113.0(13) C6 N1 C5 118.4(5) C11A C12A C13A 107.3(13) C6 N1 C12B 121.5(6) O4 C11B C12B 118.4(13) C5 N1 C12B 117.4(6) C11B C12B N1 102.0(13) C6 N1 C12A 121.9(6) C11B C12B C13B 109.3(16) C5 N1 C12A 118.6(6) N1 C12B C13B 108.3(13) C9 N2 C17 124.4(5) N2 C14 C15 109.2(5) C9 N2 C14 122.2(5) N3 C15 C14 110.5(5) C17 N2 C14 112.0(5) N3 C16 C17 110.8(5) C15 N3 C16 111.7(5) N2 C17 C16 110.0(5) C15 N3 C18 112.1(5) O6 C19 O5 121.9(8) C16 N3 C18 111.3(5) O6 C19 C20B 120.5(11) O2 C1 O1 121.1(6) O5 C19 C20B 117.5(11) O2 C1 C2 124.2(6) O6 C19 C20A 121.8(9) O1 C1 C2 114.6(6) O5 C19 C20A 116.3(10) C6 C2 C3 119.4(5) C21A C20A C25A 120.0 C6 C2 C1 118.2(5) C21A C20A C19 122.7(11) C3 C2 C1 122.5(5) C25A C20A C19 116.9(11) O3 C3 C2 122.4(5) O7A C21A C20A 118.8(10) O3 C3 C4 121.4(5) O7A C21A C22A 120.9(10) C2 C3 C4 116.1(5) C20A C21A C22A 120.0 C5 C4 C7 118.2(5) C21A C22A C23A 120.0 C5 C4 C3 121.0(5) C24A C23A C22A 120.0 C7 C4 C3 120.8(5) C25A C24A C23A 120.0 C10 C5 N1 119.9(5) O8A C25A C24A 110.4(12) C10 C5 C4 120.6(5) O8A C25A C20A 128.6(12) N1 C5 C4 119.5(5) C24A C25A C20A 120.0 N1 C6 C2 125.6(6) C21B C20B C25B 120.0 C8 C7 C4 119.2(6) C21B C20B C19 115.1(13) C7 C8 F1 118.9(6) C25B C20B C19 124.8(13) C7 C8 C9 125.1(5) O7B C21B C20B 123.4(12) F1 C8 C9 115.9(5) O7B C21B C22B 115.2(12) N2 C9 C10 122.2(5) C20B C21B C22B 120.0 N2 C9 C8 122.2(5) C21B C22B C23B 120.0 C10 C9 C8 115.6(5) C24B C23B C22B 120.0 O4 C10 C5 121.0(5) C23B C24B C25B 120.0 O4 C10 C9 117.9(5) O8B C25B C24B 123.8(14) C5 C10 C9 121.1(5) O8B C25B C20B 115.7(14) O4 C11A C12A 115.2(10) C24B C25B C20B 120.0 Figure 2. ORTEP diagram of LEV-26DHBA drawn at a probability level of 50%. H-atoms are shown by small circles of arbitrary radius. Only the major part of the disordered groups are shown for clarity. Figure 3. Packing diagram of LEV-26DHBA showing intramolecular H-bonding and strong intermolecular H-bonding. Selected H-atoms are shown for clarity. Mashhadi et al. / European Journal of Chemistry 12 (3) (2021) 323-328 327 2021 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.12.3.323-328.2134 Table 4. Hydrogen bond geometry and C-H···π interaction for LEV-26DHBA. D H A d(D-H) (Å) d(H-A) (Å) d(D-A) (Å) D-H-A (°) O1 H1 O3 0.82 1.80 2.548(6) 150.7 N3 H3 O51 0.93(6) 1.76(6) 2.633(7) 156(6) C13A H13B O62 0.96 2.64 3.588(17) 170.1 C13A H13C O7A 0.96 2.58 3.50(2) 159.0 C11B H11C O33 0.97 2.53 3.392(19) 147.5 C12B H12B O34 0.98 2.61 3.461(18) 144.7 C14 H14B F1 0.97 2.28 2.825(8) 114.9 C14 H14B O23 0.97 2.64 3.289(7) 124.7 C16 H16A O8B5 0.97 2.63 3.513(16) 152.0 C18 H18A F16 0.96 2.60 3.183(8) 119.7 C18 H18C O27 0.96 2.56 3.432(9) 151.5 O7A H7A O6 0.82 1.99 2.657(12) 137.6 O8A H8A O5 0.82 1.93 2.570(18) 134.1 C24A H24A O8A5 0.93 2.60 3.383(19) 142.7 O8B H8B O5 0.82 1.92 2.48(2) 124.7 C H π d(C-H) (Å) d(C-π) (Å) d(C-π) (Å) C-H-π (°) C18 H18B Cg18 0.96 2.76 3.665 (10) 157 Symmetry codes: 1 2-x, 1-y, 1-z; 2 2-x, 1-y, -z; 3 2-x, -y, -z; 4 1-x, -y, -z; 5 1-x, 1-y, 1-z; 6 1-x, -y, 1-z; 7 +x, +y, 1+z, 8 -x+1, -y+1, -z+1. Cg1 is the centroid of the phenyl ring (C20A-C25A). Figure 4. Packing diagram of LEV-26DHBA showing strong as well as weak H-bonding. Selected H-atoms are shown for clarity. Figure 5. Graphical representation of C-H···π interaction in the crystal packing of LEV-26DHBA. Selected H-atoms are shown for clarity. The carboxylate group F (C19/O5/O6) is, of course, planar. The dihedral angle between D/E, D/F, and E/F is 11.8(9), 9.75(1.28), and 3.72(1.52)°, respectively. This shows that the 2,6-dihydroxybenzoate molecules of the minor part are more planar as compared to the major part. Due to strong H-bonding, there exist two S(6) loops in the anion part and one in the cation part due to O-H···O bonding, also the cation and anion are linked by the strong H-bonding of N-H···O interaction (Figure 3). The weaker H-bonding joins the anions like dimmers due to C-H···O interactions with R2 2(8) loops (Figure 4). Furthermore, the C- H···O interaction between the H-atom of methyl at N3 and O- atom of the carbonyl group present in the cations link them- selves in pairs. In this way, the molecules are mainly stabilized because of these hydrogen bonding. In addition to H-bonding, comparatively weak interactions of type C-H···π and off-set π···π stacking helps in the further stabilization of the crystal packing. C-H···π interaction inter- linked cation with anion with H···π distance of 2.76 Å as displayed in Figure 5 and given in Table 4. Off-set π···π stacking interaction is found between the phenyl rings of cations. This 328 Mashhadi et al. / European Journal of Chemistry 12 (3) (2021) 323-328 2021 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.12.3.323-328.2134 interaction interlinked the cations with each other along a crystallographic axis (Figure 6). The centroid to centroid separation ranges from 3.72 to 3.87 Å, while the ring offset ranges from 1.31 to 1.64 Å. Figure 6. Graphical representation of off-set π···π stacking interaction in LEV-26DHBA. Anions and H-atoms are not shown for clarity. 4. Conclusion The present study is the preparation and characterization of a pharmaceutical organic salt of LEV and 26DHBA. Crystal structure is characterized by IR, solid state NMR and single crystal XRD. Splitting of peaks in the solid-state NMR spectrum and single-crystal XRD results concluded that the crystal is disordered. Single-crystal XRD infers that the crystal packing is mainly stabilized by strong N-H···O bonding and further stabilization in the crystal packing is due to C-H···O, C-H···π and off-set π···π stacking interactions. This multicomponent salt comprises of antibacterial drug and a GRAS antioxidant component. This combination of two pharmaceutically acceptable components in single crystalline form may be administered to the patients who require both antibacterial Levofloxacin and antioxidants. Acknowledgement We are thankful to HEC Pakistan for providing funding for the characterization. We are also thankful to Dr. Paul Hodgkinson (Durham University) for valuable suggestions during 13C and 1H NMR experiments. Supporting information CCDC-1976923 contains the supplementary crystallo- graphic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by e- mailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(0)1223-336033. Disclosure statement Conflict of interests: The authors declare that they have no conflict of interest. Author contributions: All authors contributed equally to this work. Ethical approval: All ethical guidelines have been adhered. Sample availability: Samples of the compounds are available from the author. ORCID Syed Muddassir Ali Mashhadi https://orcid.org/0000-0002-6455-7604 Muhammad Nawaz Tahir https://orcid.org/0000-0002-6815-9806 David Apperley https://orcid.org/0000-0001-7102-0314 Moazzam Hussain Bhatti https://orcid.org/0000-0003-4868-6032 Muhammad Ashfaq https://orcid.org/0000-0001-6663-8777 Uzma Yunus https://orcid.org/0000-0002-8261-0595 References [1]. Mashhadi, S. M. A.; Yunus, U.; Bhatti, M. H.; Ahmed, I.; Tahir, M. N. J. Mol. Struct. 2016, 1117, 17–21. [2]. Mashhadi, S. M. A.; Yunus, U.; Bhatti, M. H. J. Mol. Struct. 2021, 1233 (130015), 130015. [3]. Mashhadi, S. M. A.; Yunus, U.; Bhatti, M. H.; Tahir, M. N. J. Mol. Struct. 2014, 1076, 446–452. [4]. Mashhadi, S. M. A.; Batsanov, A. S.; Sajjad, S. A.; Nazir, Y.; Bhatti, M. H.; Yunus, U. J. Mol. Struct. 2021, 1226 (129388), 129388. [5]. Mashhadi, S. M. A.; Yufit, D.; Liu, H.; Hodgkinson, P.; Yunus, U. J. Mol. Struct. 2020, 1219 (128621), 128621. [6]. Lehn, J.-M. Science 2002, 295 (5564), 2400–2403. [7]. Cram, D. J. Angew. 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Pharm. Investig. 2017, 47 (6), 583–591. Copyright © 2021 by Authors. This work is published and licensed by Atlanta Publishing House LLC, Atlanta, GA, USA. The full terms of this license are available at http://www.eurjchem.com/index.php/eurjchem/pages/view/terms and incorporate the Creative Commons Attribution-Non Commercial (CC BY NC) (International, v4.0) License (http://creativecommons.org/licenses/by-nc/4.0). By accessing the work, you hereby accept the Terms. This is an open access article distributed under the terms and conditions of the CC BY NC License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited without any further permission from Atlanta Publishing House LLC (European Journal of Chemistry). No use, distribution or reproduction is permitted which does not comply with these terms. Permissions for commercial use of this work beyond the scope of the License (http://www.eurjchem.com/index.php/eurjchem/pages/view/terms) are administered by Atlanta Publishing House LLC (European Journal of Chemistry). http://www.ccdc.cam.ac.uk/data_request/cif mailto:data_request@ccdc.cam.ac.uk https://orcid.org/0000-0002-6455-7604 https://orcid.org/0000-0002-6815-9806 https://orcid.org/0000-0001-7102-0314 https://orcid.org/0000-0003-4868-6032 https://orcid.org/0000-0001-6663-8777 https://orcid.org/0000-0002-8261-0595 http://www.eurjchem.com/index.php/eurjchem/pages/view/terms http://creativecommons.org/licenses/by-nc/4.0 http://www.eurjchem.com/index.php/eurjchem/pages/view/terms 1. Introduction 2. Experimental 2.1. Instrumentation 2.2. Preparation of LEV-26DHBA 3. Result and discussion 3.1. Characterization 3.2. Single crystal structure 4. Conclusion Acknowledgement Supporting information Disclosure statement ORCID References PrintField10: PrintField11: PrintField12: PrintField13: PrintField14: PrintField15: PrintField20: PrintField21: PrintField22: PrintField23: PrintField24: PrintField25: