Structure and crystal packing of the antibacterial drug 1-{[(5-nitro-2-furanyl)methylene]amino}-2,4-imidazolidinedione (nitrofurantoin)

Bertolasi, Valerio; Gilli, Paola; Ferretti, Valeria; Gilli, Gastone

doi:10.1107/s010827019201062x

Cited by 14 publications

(9 citation statements)

References 8 publications

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“…Nitrofurantoin, similarly like furazidin, has two polymorphic forms, a triclinic one and a monoclinic one. These polymorphs, designated as α and β forms, crystallize in P-1 and P21/n space groups, respectively (the respective CCDC refcodes for these structures are LABJON01 and LABJON), (Bertolasi et al, 1993;Pienaar et al, 1993), both with one nitrofurantoin molecule in an asymmetric part of a unit cell. The first of these polymorphs, the triclinic one, display very similar intermolecular interactions to the triclinic form of furazidin (form I), with dimers interacting via N-H...O from hydantoin rings ( Figure S11a, Supporting Information).…”

Section: Comparison Of Z' = 1 (Form Ii) and Z' = 2 (Form I) Polymorphsmentioning

confidence: 99%

Crystal structures of two furazidin polymorphs revealed by a joint effort of crystal structure prediction and NMR crystallography

Dudek

Paluch

Pindelska

2020

Acta Crystallogr B Struct Sci Cryst Eng Mater

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This work presents the crystal structure determination of two elusive polymorphs of furazidin, an antibacterial agent, employing a combination of crystal structure prediction (CSP) calculations and an NMR crystallography approach. Two previously uncharacterized neat crystal forms, one of which has two symmetry-independent molecules (form I), whereas the other one is a Z 0 = 1 polymorph (form II), crystallize in P2 1 /c and P1 space groups, respectively, and both are built by different conformers, displaying different intermolecular interactions. It is demonstrated that the usage of either CSP or NMR crystallography alone is insufficient to successfully elucidate the abovementioned crystal structures, especially in the case of the Z 0 = 2 polymorph. In addition, cases of serendipitous agreement in terms of 1 H or 13 C NMR data obtained for the CSP-generated crystal structures different from the ones observed in the laboratory (false-positive matches) are analyzed and described. While for the majority of analyzed crystal structures the obtained agreement with the NMR experiment is indicative of some structural features in common with the experimental structure, the mentioned serendipity observed in exceptional cases points to the necessity of caution when using an NMR crystallography approach in crystal structure determination. research papers Acta Cryst. (2020). B76, 322-335 Marta K. Dudek et al. Two furazidin polymorphs 323 research papers Acta Cryst. (2020). B76, 322-335 Marta K. Dudek et al. Two furazidin polymorphs 331 Figure 10Hydrogen-bonding pattern in the experimental crystal structure of form I (a) and in the third-lowest-energy crystal structure (b), built by the same conformers as the experimental structure; hydrogen bonds are marked with dotted green lines.

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Section: Comparison Of Z' = 1 (Form Ii) and Z' = 2 (Form I) Polymorphsmentioning

confidence: 99%

Crystal structures of two furazidin polymorphs revealed by a joint effort of crystal structure prediction and NMR crystallography

Dudek

Paluch

Pindelska

2020

Acta Crystallogr B Struct Sci Cryst Eng Mater

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“…This is the reason why, here, calculations have been performed on the NF-DMAP (1:1, monomer) salt which has taken into account all the H-bond interactions. The three crystal systems considered in this study, NF-DMAP (1:1), NF (monomer) and DMAP (monomer), are known [15,18,38]. Hence, their crystallographic data have been served to obtain the initially optimized structure with energy minima.…”

Section: Geometry Optimization and Energiesmentioning

confidence: 99%

“…The main purpose of our work is to compare two different functional in DFT to understand the geometry and reactivity of NF-DMAP salt. The ground state optimized geometries of NF-DMAP (B3LYP), NF-DMAP (wB97X-D), NF (wB97X-D and B3LYP) and DMAP (wB97X-D and B3LYP) are shown in Figures 1 and 2 Table S1, combined with the crystallographic data of both salt and API [15,18]. The molecular geometries of NF-DMAP calculated using B3LYP and wB97X-D methods are compared with the geometry of a single molecule of NF.…”

Section: Geometry Optimization and Energiesmentioning

confidence: 99%

“…NF prevents several bacterial enzyme systems (gram-positive and gram-negative bacteria) and has broad antibacterial activity [12]. The dissolution rate of NF in water is low [10], and also its bioavailability drops upon storage [13][14][15][16]. Due to these paucities and to enhance the physicochemical stability (solubility and bioavailability) of NF tablets, preparation of pharmaceutical salt of NF could potentially present significant opportunities [17].…”

Section: Introductionmentioning

confidence: 99%

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Structural and Reactivity Analyses of Nitrofurantoin–4-dimethylaminopyridine Salt Using Spectroscopic and Density Functional Theory Calculations

et al. 2019

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Pharmaceutical salt, nitrofurantoin–4-dimethylaminopyridine (NF-DMAP), along with its native components NF and DMAP are scrutinized by FT-IR and FT-Raman spectroscopy along with density functional theory so that an insight into the H-bond patterns in the respective crystalline lattices can be gained. Two different functionals, B3LYP and wB97X-D, have been used to compare the theoretical results. The FT-IR spectra obtained for NF-DMAP and NF clearly validate the presence of C33–H34⋅⋅⋅O4 and N23–H24⋅⋅⋅N9 hydrogen bonds by shifting in the stretching vibration of –NH and –CH group of DMAP+ towards the lower wavenumber side. To explore the significance of hydrogen bonding, quantum theory of atoms in molecules (QTAIM) has been employed, and the findings suggest that the N23–H24⋅⋅⋅N9 bond is a strong intermolecular hydrogen bond. The decrement in the HOMO-LUMO gap, which is calculated from NF → NF-DMAP, reveals that the active pharmaceutical ingredient is chemically less reactive compared to the salt. The electrophilicity index (ω) profiles for NF and DMAP confirms that NF is acting as electron acceptor while DMAP acts as electron donor. The reactive sites of the salt are plotted by molecular electrostatic potential (MEP) surface and calculated using local reactivity descriptors.

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“…Where applicable, one-way analysis of variance (ANOVA) and t tests were performed using the data analysis tool in MS Excel 2020 (Microsoft Corp., Redmond, WA, USA) software with a confidence level of 95% (p < 0.05).■ RESULTS AND DISCUSSIONExploratory Structural and Spectroscopic Analysis. All of the anhydrous and hydrated nitrofurantoin solid-state forms exhibit fairly simple molecular arrangements and hydrogen-bonding networks.19,32 Crystals of NF-MH II exist within the orthorhombic space group, Pcba, and exhibit at least two distinct packing motifsa C(12) chain comprised of N− H•••O and CO•••H hydrogen bonds with water molecules acting as the bridging agents as well as more intramolecular R 1 ring-type formation between the water molecules and the 5-nitrofuran ring of the nitrofurantoin moieties (Figure S1). Similarly, NF-MH I, which exists within the P2 1 /n space group, exhibits C(6) chain-and R 4 3 (10) ring-type hydrogen-bonding interactions involving N−H•••O and CO•••H which are linked by the water molecules.…”

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confidence: 99%

Elucidating the Dehydration Mechanism of Nitrofurantoin Monohydrate II Using Low-Frequency Raman Spectroscopy

Remoto

Bērziņš

Fraser‐Miller

et al. 2022

Crystal Growth & Design

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The dehydration of nitrofurantoin monohydrate II was monitored under different isothermal conditions (100, 105, 110, 115, and 120 °C) using Raman spectroscopy in the low-(−300 to 15 and 15 to 300 cm −1 ) and mid-(300 to 1800 cm −1 ) frequency regions. Clear and subtle spectral differences were observed for Raman spectra in the respective domains for solidstate transformations. Multivariate curve resolution was used to extract the information on the solid-state forms present and their relative abundances during the isothermal dehydration experiments. Theoretical modeling of nitrofurantoin hydrates (nitrofurantoin monohydrates I and II) and anhydrous forms (α and β) was carried out using density functional theory with periodic boundary conditions to support the interpretation of low-energy vibrational modes. Midfrequency Raman spectroscopy detected the onset of the dehydration process (where observed) of nitrofurantoin monohydrate II ∼100−300 s before the low-frequency Raman spectral domain depending on the isothermal condition. This was attributed to the change of order during the process, where disruption of localized molecular arrangements within the monohydrate crystal structure is first expected to occur.

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Structure and crystal packing of the antibacterial drug 1-{[(5-nitro-2-furanyl)methylene]amino}-2,4-imidazolidinedione (nitrofurantoin)

Cited by 14 publications

References 8 publications

Crystal structures of two furazidin polymorphs revealed by a joint effort of crystal structure prediction and NMR crystallography

Crystal structures of two furazidin polymorphs revealed by a joint effort of crystal structure prediction and NMR crystallography

Structural and Reactivity Analyses of Nitrofurantoin–4-dimethylaminopyridine Salt Using Spectroscopic and Density Functional Theory Calculations

Elucidating the Dehydration Mechanism of Nitrofurantoin Monohydrate II Using Low-Frequency Raman Spectroscopy

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