| 1. |
- Srivastava, Karnica, et al.
(author)
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Vibrational analysis and chemical activity of paracetamol-oxalic acid cocrystal based on monomer and dimer calculations : DFT and AIM approach
- 2016
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In: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 6:12, s. 10024-10037
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Journal article (peer-reviewed)abstract
- The study of structural and spectral characteristics of a paracetamol-oxalic acid (PRA-OXA) cocrystal has been carried out using two models (monomer and dimer), with the aim to understand the supramolecular structure and intramolecular interactions within the cocrystal. The cocrystal has been characterized by infrared and Raman spectroscopy combined with quantum chemical calculations molecular electrostatic potential surface (MEPS), frontier orbital analysis and electronic reactivity descriptors were used to understand the role of interactions involved in affecting the chemical reactivity of individual molecules in the cocrystal. It is observed that the C=O, N-H and O-H groups of paracetamol are involved in hydrogen bonds to form cocrystals. NBO analysis suggests that the two types of interactions LP(1)(N8) -> pi*(C9-O10) and LP(2)(O10) -> sigma*(O25-H28) are responsible for the stability of the molecule. AIM analysis suggested that the non-covalent interactions are moderate in nature. The calculated HOMO-LUMO energies reveal that the charge transfer occurs within the cocrystal. Chemical reactivity parameters show that the cocrystal is more active than paracetamol.
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| 2. |
- Verma, Priya, et al.
(author)
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Molecular Structure, Spectral Investigations, Hydrogen Bonding Interactions and Reactivity-Property Relationship of Caffeine-Citric Acid Cocrystal by Experimental and DFT Approach
- 2021
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In: Frontiers in Chemistry. - : Frontiers Media S.A.. - 2296-2646. ; 9
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Journal article (peer-reviewed)abstract
- The pharmaceutical cocrystal of caffeine-citric acid (CAF-CA, Form II) has been studied to explore the presence of hydrogen bonding interactions and structure-reactivity-property relationship between the two constituents CAF and Citric acid. The cocrystal was prepared by slurry crystallization. Powder X-ray diffraction (PXRD) analysis was done to characterize CAF-CA cocrystal. Also, differential scanning calorimetry (DSC) confirmed the existence of CAF-CA cocrystal. The vibrational spectroscopic (FT-IR and FT-Raman) signatures and quantum chemical approach have been used as a strategy to get insights into structural and spectral features of CAF-CA cocrystal. There was a good correlation among the experimental and theoretical results of dimer of cocrystal, as this model is capable of covering all nearest possible interactions present in the crystal structure of cocrystal. The spectroscopic results confirmed that (O33-H34) mode forms an intramolecular (C25 = O28∙∙∙H34-O33), while (O26-H27) (O39-H40) and (O43-H44) groups form intermolecular hydrogen bonding (O26-H27∙∙∙N24-C22, O39-H40∙∙∙O52 = C51 and O43-H44∙∙∙O86 = C83) in cocrystal due to red shifting and increment in bond length. The quantum theory of atoms in molecules (QTAIM) analysis revealed (O88-H89∙∙∙O41) as strongest intermolecular hydrogen bonding interaction with interaction energy −12.4247 kcal mol−1 in CAF-CA cocrystal. The natural bond orbital analysis of the second-order theory of the Fock matrix highlighted the presence of strong interactions (N∙∙∙H and O∙∙∙H) in cocrystal. The HOMO-LUMO energy gap value shows that the CAF-CA cocrystal is more reactive, less stable and softer than CAF active pharmaceutical ingredients. The electrophilic and nucleophilic reactivities of atomic sites involved in intermolecular hydrogen bond interactions in cocrystal have been demonstrated by mapping electron density isosurfaces over electrostatic potential i.e. plotting molecular electrostatic potential (MESP) map. The molar refractivity value of cocrystal lies within the set range by Lipinski and hence it may be used as orally active form. The results show that the physicochemical properties of CAF-CA cocrystal are enhanced in comparison to CAF (API).
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| 3. |
- Srivastava, Karnica, et al.
(author)
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Molecular structure, spectroscopic signature and reactivity analyses of paracetamol hydrochloride monohydrate salt using density functional theory calculations
- 2019
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In: CrystEngComm. - : Royal Society of Medicine Press. - 1466-8033. ; 21:5, s. 857-865
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Journal article (peer-reviewed)abstract
- The aim of this study was to understand the role of the intermolecular hydrogen bond interactions present in paracetamol hydrochloride monohydrated salt. Paracetamol hydrochloride monohydrate salt (PRA-HCl) and paracetamol (form I) were investigated via vibrational (FT-IR and FT-Raman) spectroscopy and density functional theory (DFT) to gain insight into the hydrogen bond patterns present in these crystalline materials. Two different density functionals, wB97X-D and M062X, were used for the comparison of the results. The geometrical parameters of PRA-HCl and form I obtained using these functional were compared with the crystallographic data, which proved the existence of intra-molecular and intermolecular hydrogen bonds. The C10O2 group of form I forms an intramolecular hydrogen bond, while the O1–H18 group of PRA-HCl forms an intermolecular hydrogen bond with a chloride ion (Cl−), resulting in the elongation of the bond length and shift to a lower wavenumber for the O1–H18 group. To examine the potency of hydrogen bonding, quantum theory of atoms in molecules (QTAIM) calculations were performed and the results suggested that O1–H18⋯Cl22 is a strong intermolecular hydrogen bond. The chemical reactivity parameters reveal that the PRA-HCl and PRA-OXA cocrystals are more reactive and softer (low HOMO–LUMO energy gap) in comparison to paracetamol (form I).
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