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Study of hydrogen bonding interactions and chemical reactivity analysis of nitrofurantoin–3-aminobenzoic acid cocrystal using quantum chemical and spectroscopic (IR, Raman, 13C SS-NMR) approach

Abstract

The investigations of structural reactivity, molecular interactions and vibrational characterization of pharmaceutical drug are helpful to understand their behaviour. The aim of this study is to determine the molecular, electronic and chemical properties of an antibiotic drug, nitrofurantoin (NF), after cocrystallisation with 3-aminorbenzoic acid (3ABA) and to understand as to how those changes lead to variation of properties in the cocrystal, NF-3ABA. NF-3ABA formation is explained by the stabilization via hydrogen-bond network between NF and 3ABA molecules. It is thoroughly characterized by IR, Raman and CP-MAS solid-state 13C NMR techniques, along with quantum chemical calculations. The indications of IR, Raman, and 13C NMR showed that imide N-H23 and C12=O of NF interacts with the acid C=O and –OH groups in 3-ABA, respectively. Therefore IR, Raman, and 13C NMR spectra verified the formation of NH···O and OH···O hydrogen bonds. To study hydrogen bonding interactions theoretically in NF-3ABA, two functionals; B3LYP and wB97X-D have been used. A comparison is made between the results obtained by B3LYP and those predicted at wB97X-D level. It is found that wB97X-D is best applied density functional theory (DFT) functional to describe the hydrogen bonding interactions. The strength and nature of hydrogen bonding in NF-3ABA have been analysed by quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analysis. To validate the results obtained by QTAIM theory and to study the long-range forces, such as van der Waals interactions, steric effects in NF-3ABA, the reduced density gradient (RDG) and the isosurface have been plotted using Multiwfn software. QTAIM and isosurface analysis suggested that the hydrogen bonding interactions present in the NF-3ABA are moderate in nature. The calculated HOMO–LUMO energy gap shows that the NF-3ABA is more active than NF and 3ABA. Chemical reactivity descriptors are calculated to understand the various aspects of pharmacological sciences. Chemical reactivity parameters show that the NF-3ABA is more softer and chemically more reactive than NF. The results suggest that cocrystals can be a feasible alternative for positively changing the targetted physicochemical properties of an active pharmaceutical ingredient (API).

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Publication details

The article was received on 08 May 2017, accepted on 16 Jun 2017 and first published on 16 Jun 2017


Article type: Paper
DOI: 10.1039/C7CE00864C
Citation: CrystEngComm, 2017, Accepted Manuscript
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    Study of hydrogen bonding interactions and chemical reactivity analysis of nitrofurantoin–3-aminobenzoic acid cocrystal using quantum chemical and spectroscopic (IR, Raman, 13C SS-NMR) approach

    A. Shukla, E. Khan, K. Srivastava, K. Sinha, P. Tandon and V. R. Vangala, CrystEngComm, 2017, Accepted Manuscript , DOI: 10.1039/C7CE00864C

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