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Structural evidence of polymorphism and conformational isomorphism of a somewhat flexible molecule: m-anisic acid

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Abstract

m-Anisic acid is generally recognized as a safe (GRAS) flavouring substance. Its GRAS status and the functional groups present in the molecule make it an interesting candidate for pharmaceutical co-crystallization studies. The knowledge of m-anisic acid crystalline structure/polymorphic behaviour is important information for its applications. In this work, a crystalline structure of m-anisic acid form I, T fus = 105 °C, was solved by X-ray diffraction: monoclinic, space group P21/n, with a = 13.8075(5) Å, b = 5.0221(2) Å, c = 21.4455(8) Å, β = 99.325(3)°, Mr = 331.37, V = 1467.44(10) Å3, Z = 8 and R = 0.0395 (CCDC No. 985352). A recent paper by Raffo et al. (J Mol Struct 1070:86–93, 2014) (CCDC No. 985637) also resolved the structure, and within experimental error, the two structures are equal. The molecular flexibility of m-anisic acid results in the presence of two conformers in the unit cell, a rare case of conformational isomorphism. These two conformers were found by ab initio calculations to differ in energy by 4.9 kJ mol−1. Solid samples were generated by crystallization from solutions and by melt cooling. Using a multidisciplinary approach involving thermal analysis (DSC, PLTM), infrared spectroscopy and X-ray powder diffraction, a new monotropic solid form II, T fus = 94 °C, was identified and characterized. Polymorph II slowly transforms into polymorph I at room temperature.

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Acknowledgements

P. S. Pereira Silva acknowledges the support by Fundação para a Ciência e a Tecnologia, under the scholarship SFRH/BPD/84173/2012. The Center for Pharmaceutical Studies (CEF), the Coimbra Chemistry Centre (CCC) and Centro de Estudos de Materiais por Difracção de Raios-X (CEMDRX) are supported by the Fundação para a Ciência e a Tecnologia (FCT), Portuguese Agency for Scientific Research, through the projects PEst-OE/SAU/UI0177/2014, PEst-OE/QUI/UI0313/2014 and PEst-C/FIS/UI0036/2011, respectively.

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Authors and Affiliations

  1. CEMDRX, Physics Department, University of Coimbra, 3004-516, Coimbra, Portugal

    Pedro S. Pereira Silva & Manuela Ramos Silva

  2. CEF, Faculty of Pharmacy, University of Coimbra, 3000-548, Coimbra, Portugal

    Ricardo A. E. Castro & João Canotilho

  3. CCC, Department of Chemistry, University of Coimbra, 3004-535, Coimbra, Portugal

    Elodie Melro, Teresa M. R. Maria & M. Ermelinda S. Eusébio

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  1. Pedro S. Pereira Silva
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Correspondence to Pedro S. Pereira Silva or Ricardo A. E. Castro.

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Pereira Silva, P.S., Castro, R.A.E., Melro, E. et al. Structural evidence of polymorphism and conformational isomorphism of a somewhat flexible molecule: m-anisic acid. J Therm Anal Calorim 120, 667–677 (2015). https://doi.org/10.1007/s10973-014-4289-y

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