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Thermal analysis, structure, spectroscopy and DFT calculations of a pharmaceutical cocrystal of salicylic acid and salicylamide

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Abstract

The pharmaceutical cocrystal of salicylic acid (C7H6O3 or H2Sal) and salicylamide (C7H7NO2 or SAM) was synthesized and characterized by various techniques. The differential scanning calorimetry results confirmed the eutectic fusion showing the characteristic of the endothermic sharp peak of the solidus temperature at 108 °C. X-ray crystal structure of cocrystal is orthorhombic with space group Pna2(1). Cocrystal consists of H2Sal and a distorted phenolic group of SAM. The packing diagram of cocrystal H2Sal·SAM clearly confirmed the \(R_{8}^{2}\) acid–amide dimer heterosynthons and other inter- and intramolecular interaction bonds to stabilize the structure. In addition, the strength of the hydrogen bonds is studied using the vibrational spectral measurements, confirming the band shifting due to the intermolecular interactions. The identity of compounds by matching the absorbance spectrum was confirmed by ultraviolet spectroscopy technique. Furthermore, the experimental studies were supported by calculation results using density functional B3LYP methods with the standard 6-311++G(d,p) basis set level. The parameters such as bond lengths, bond angles and Mulliken atomic charges values have been calculated and compared, confirmed the interactions and charge transfers. The frontier molecular orbitals (HOMO–LUMO) illustrated the lower band-gap value suggesting the possible pharmaceutical activity of this as obtained H2Sal·SAM cocrystal.

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Acknowledgements

We gratefully acknowledge the Thaksin University for the research grants via the Research and Development Institute, Thaksin University (RDITSU), and the National Research Management System (NRMS); project codes: 111006 and 184788.

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Authors and Affiliations

  1. Inorganic and Materials Chemistry Research Unit, Faculty of Science, Thaksin University, Muang, Songkhla, 90000, Thailand

    Hirihattaya Phetmung & Kanlayanee Musikapong

  2. Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, 90112, Thailand

    Teerapol Srichana

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  1. Hirihattaya Phetmung
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  2. Kanlayanee Musikapong
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  3. Teerapol Srichana
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Correspondence to Hirihattaya Phetmung.

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Phetmung, H., Musikapong, K. & Srichana, T. Thermal analysis, structure, spectroscopy and DFT calculations of a pharmaceutical cocrystal of salicylic acid and salicylamide. J Therm Anal Calorim 138, 1207–1220 (2019). https://doi.org/10.1007/s10973-019-08794-5

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