Ezetimibe (EZT) being an anticholesterol drug is frequently used for the reduction of elevated blood cholesterol levels. With the purpose of improving the physicochemical properties of EZT, in the present study, cocrystals of ezetimibe with L-proline have been studied. Theoretical geometry optimization of EZT-L-proline cocrystal, energies, and structure–activity relationship was carried out at the DFT level of theory using B3LYP functional complemented by 6-311++G(d,p) basis set. To better understand the role of hydrogen bonding, two different models (EZT + L-proline and EZT + 2L-proline) of EZT-L-proline cocrystal were studied. Spectral techniques (FTIR and FT-Raman) combined with quantum chemical methodologies were successfully implemented for the detailed vibrational assignment of fundamental modes. It is a zwitterionic cocrystal hydrogen bonded with the OH group of EZT and the COO− group of L-proline. The existence and strength of hydrogen bonds were examined by a natural bond orbital analysis (NBO) supported by the quantum theory of atoms in molecule (QTAIM). Chemical reactivity was reflected by the HOMO–LUMO analysis. A smaller energy gap in the cocrystal in comparison to API shows that a cocrystal is softer and chemically more reactive. MEPS and Fukui functions revealed the reactive sites of cocrystals. The calculated binding energy of the cocrystal from counterpoise method was −11.44 kcal/mol (EZT + L-proline) and −26.19 kcal/mol (EZT + 2L-proline). The comparative study between EZT-L-proline and EZT suggest that cocrystals can be better used as an alternative to comprehend the effect of hydrogen bonding in biomolecules and enhance the pharmacological properties of active pharmaceutical ingredients (APIs).

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.

In this work, we have performed the extraction of yohimbine hydrochloride (C 21 H 27 ClN 2 O 3 ) (YHCl). The optimized geometry, total energy, potential energy surface and vibrational wavenumbers of YHCl have been determined by using ab initio Hartree-Fock (HF) and density functional theory (DFT/B3LYP) method with 6-311++G(d,p) basis set. The calculated wavenumbers are scaled by a proper scaling factor. A selected number of vibrational assignment is provided for the observed Raman and IR spectra.

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In this communication, we have presented the geometry optimization, complete vibrational study with potential energy distribution (PED) and frontier orbital energy gap for the 10-Acetyl-10H-phenothiazine 5-oxide (APTZ) molecule using ab initio Hartree-Fock (HF) and density functional theory (DFT/B3LYP) method employing 6-311++G(d,p) basis set. The calculated IR and Raman spectra with their intensities, molecular electrostatic potential (MESP) surface and highest occupied molecular orbital (HOMO) - lowest unoccupied molecular orbital (LUMO) plot have been given. DOI: http://dx.doi.org/10.3126/bibechana.v9i0.7151 BIBECHANA 9 (2013) 38-49

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