Dataset Information

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

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 + coformer) 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 reported by 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 the characterization and validation of NIC-OXA salt. The spectroscopic signatures revealed that (N7-H8)/(N23-H24) of the pyridine ring of NIC, (C═O), and (C-O) groups of OXA were forming the intermolecular hydrogen bonding (N-H⋯O-C), (C-H⋯O═C), and (N-H⋯O═C), respectively, in NIC-OXA salt. Additionally, the 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 analysis was 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 orbital (FMO) 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 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 the formation of NIC-OXA salt, confirming the presence of hydrogen bonding interactions (N7-H8⋯O5-C6) and (N23-H24⋯O2-C3). Lipinski's rule was applied to check the activeness of salt as an orally active form. The results shed light on several features of NIC-OXA salt that can further lead to the improvement in the physicochemical properties of NIC.

SUBMITTER: Verma P

PROVIDER: S-EPMC8965448 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Verma Priya P Srivastava Anubha A Tandon Poonam P Shimpi Manishkumar R MR

Frontiers in chemistry 20220315

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 + coformer) 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 reported by using vibrational spectroscopic signatures ( ...[more]

PMID: 35372271

Similar Datasets

Project description:In the present work, nicotinamide-oxalic acid (NIC-OXA, form I) salt was crystallized by slow evaporation of an aqueous solution. To understand the molecular structure and spectroscopic properties of NIC after co-crystallization with OXA, experimental infrared (IR), Raman spectroscopic signatures, X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC) techniques were used to characterize and validate the salt. The density functional theory (DFT) methodology was adopted to perform all theoretical calculations by using the B3LYP/6-311++G (d, p) functional/basis set. The experimental geometrical parameters were matched in good correlation with the theoretical parameters of the dimer than the monomer, due to the fact of covering the nearest hydrogen bonding interactions present in the crystal structure of the salt. The IR and Raman spectra of the dimer showed the red (downward) shifting and broadening of bands among (N15-H16), (N38-H39), and (C13=O14) bonds of NIC and (C26=O24), (C3=O1), and (C26=O25) groups of OXA, hence involved in the formation of NIC-OXA salt. The atoms in molecules (AIM) analysis revealed that (N8-H9···O24) is the strongest (conventional) intermolecular hydrogen bonding interaction in the dimer model of salt with the maximum value of interaction energy -12.1 kcal mol-1. Furthermore, the natural bond orbital (NBO) analysis of the Fock matrix showed that in the dimer model, the (N8-H9···O24) bond is responsible for the stabilization of the salt with an energy value of 13.44 kcal mol-1. The frontier molecular orbitals (FMOs) analysis showed that NIC-OXA (form I) salt is more reactive and less stable than NIC, as the energy gap of NIC-OXA (form I) salt is less than that of NIC. The global and local reactivity descriptor parameters were calculated for the monomer and dimer models of the salt. The electrophilic, nucleophilic, and neutral reactive sites of NIC, OXA, monomer, and dimer models of salt were visualized by plotting the molecular electrostatic potential (MESP) surface. The study provides valuable insights into combining both experimental and theoretical results that could define the physicochemical properties of molecules.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets