This is an Accepted Manuscript, which has been through the Royal Society of Chemistry peer review process and has been accepted for publication.Accepted Manuscripts are published online shortly after acceptance, before technical editing, formatting and proof reading. Using this free service, authors can make their results available to the community, in citable form, before we publish the edited article. We will replace this Accepted Manuscript with the edited and formatted Advance Article as soon as it is available.You can find more information about Accepted Manuscripts in the author guidelines. 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. 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).

Ampicillin trihydrate chemically associated to C 16 H 19 N 3 O 4 S·3H 2 O empirical formula, is a semi-synthetic amino-penicillin derived from the elementary penicillin nucleus, 6aminopenicillanic acid. It is a very common antibiotic that is active against an extensive range of Gram-positive and Gram-negative organisms. It is used to treat certain varieties of bacterial infections, like gonorrhea and infections of the urinary, intestinal and respiratory tracts. In the present effort, quantum chemical calculations of molecular geometries (bond lengths and bond angles) and bonding features of monomer and dimer of ampicillin trihydrate in the ground state have been carried out due to its biological and industrial importance. The optimized geometry and wavenumber of the vibrational bands of the molecule have been calculated by ab-initio density functional theory (DFT) using Becke's three-parameters hybrid functional (B3LYP) with 6-311++G(d,p) basis set. Vibrational wavenumbers were compared with the observed FT-Raman and FT-IR spectra. Molecular electrostatic potential (MEP) has also been plotted for predicting the molecule reactivity towards positively or negatively charged reactants and it shows that electropositive potential is visualized in the vicinity of the -NH 3 group and electropositive region is found near the H 2 O molecule in both monomer and dimer. HOMO-LUMO analysis has been done to describe the way the molecule interacts with other species. Natural bond orbitals (NBO) analysis has been carried out to inspect the intra-and inter-molecular hydrogen-bonding, conjugative and hyperconjugative interactions and their second order stabilization energy E (2) . Nonlinear optical (NLO) analysis has also been performed to study the non-linear optical properties of the molecule by computing the first hyperpolarizability (β 0 ). The variation of thermodynamic properties with temperature has been studied. Topological parameters at bond critical points (BCP) have been evaluated by 'Quantum theory of atoms in molecules' (QTAIM).

The cocrystal of nitrofurantoin with urea (C8H6N4O5)·(CH4N2O), a non-ionic supramolecular complex, has been studied.

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Paracetamol–4,4′-bipyridine cocrystal studied using vibrational spectroscopic and quantum chemical approach.