AUTHOR=Verma Priya , Srivastava Anubha , Tandon Poonam , Shimpi Manishkumar R. 

TITLE=Experimental and Quantum Chemical Studies of Nicotinamide-Oxalic Acid Salt: Hydrogen Bonding, AIM and NBO Analysis

JOURNAL=Frontiers in Chemistry

VOLUME=Volume 10 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2022.855132

DOI=10.3389/fchem.2022.855132

ISSN=2296-2646

ABSTRACT=The computational modeling supported with experimental results can explain the overall structural packing by predicting the hydrogen bond interactions present in any cocrystals (active pharmaceutical ingredients + co-former) as well as salts. In this context, the hydrogen bonding synthons, physiochemical properties (chemical reactivity and stability) and drug likeliness behavior of proposed nicotinamide-oxalic acid (NIC-OXA) salt have been reportedby using vibrational spectroscopic signatures (IR and Raman spectra) and quantum chemical calculations. The NIC-OXA salt was prepared by reactive crystallization method. X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) techniques were used for characterization and validation of NIC-OXA salt. The spectroscopic signatures revealed that (N7-H8)/(N23-H24) of pyridine ring of NIC, (C=O) and (C-O) groups of OXA were forming the intermolecular hydrogen bonding (N7-H8•••O5-C6), (N23-H24•••O2-C3), (C10-H22•••O1=C3), (C26-H38•••O4=C6), (N7-H8•••O1=C3) and (N23-H24•••O4=C6) in NIC-OXA salt. Additionally, quantum theory of atoms in molecules (QTAIM) showed that (C10-H22•••O1) and (C26-H38•••O4) are two unconventional hydrogen bonds present in NIC-OXA salt. Also, the natural bond orbital (NBO) analysis were performed to find the charge transfer interactions and revealed the strongest hydrogen bonds (N7-H8•••O5)/(N23-H24•••O2) in NIC-OXA salt. The frontier molecular orbitals (FMOs) analysis suggested more reactivity and less stability of NIC-OXA salt in comparison to NIC-CA cocrystal and NIC. The global and local reactivity descriptors were calculated and predicted that NIC-OXA salt is softer than NIC-CA cocrystal and NIC. From MESP of NIC-OXA salt, it is clear that electrophilic (N7-H8)/(N23-H24), (C6=O4)/(C3=O1) and nucleophilic (C10-H22)/(C26-H38), (C6-O5)/(C3-O2) reactive groups in NIC and OXA, respectively, neutralize after formation of NIC-OXA salt, confirm the presence of hydrogen bonding interactions (N7-H8•••O5-C6) and (N23-H24•••O2-C3). The Lipinski rule was applied to check the activeness of salt as orally active form. The results shed light on the several features of NIC-OXA salt which can further lead to improvement in the physicochemical properties of NIC.