{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T16:39:45Z","timestamp":1787589585284,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Tafamidis, chemical formula C14H7Cl2NO3, is a drug used to delay disease progression in adults suffering from transthyretin amyloidosis, and is marketed worldwide under different tradenames as a free acid or in the form of its meglumine salt. The free acid (CAS no. 594839-88-0) is reported to crystallize as distinct (polymorphic) crystal forms, the thermal stability and structural features of which remained thus far undisclosed. In this paper, we present\u2014by selectively isolating highly pure batches of Tafamidis Form 1 and Tafamidis Form 4\u2014the full characterization of these solids, in terms of crystal structures (determined using state-of-the-art structural powder diffraction methods) and spectroscopic and thermal properties. Beyond conventional thermogravimetric and calorimetric analyses, variable-temperature X-ray diffraction was employed to measure the highly anisotropic response of these (poly)crystalline materials to thermal stimuli and enabled the determination of the linear and volumetric thermal expansion coefficients and of the related indicatrix. Both crystal phases are monoclinic and contain substantially flat and \u03c0-\u03c0 stacked Tafamidis molecules, arranged as centrosymmetric dimers by strong O-H\u00b7\u00b7\u00b7O bonds; weaker C-H\u00b7\u00b7\u00b7N contacts give rise, in both polymorphs, to infinite ribbons, which guarantee the substantial stiffness of the crystals in the direction of their elongation. Complete knowledge of the structural models will foster the usage of full-pattern quantitative phase analyses of Tafamidis in drug and polymorphic mixtures, an important aspect in both the forensic and the industrial sectors.<\/jats:p>","DOI":"10.3390\/molecules27217411","type":"journal-article","created":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T06:01:28Z","timestamp":1667282488000},"page":"7411","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Thermal and Structural Characterization of Two Crystalline Polymorphs of Tafamidis Free Acid"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9921-2350","authenticated-orcid":false,"given":"Norberto","family":"Masciocchi","sequence":"first","affiliation":[{"name":"Dipartimento di Scienza e Alta Tecnologia e To.Sca.Lab., Universit\u00e0 dell\u2019Insubria, Via Valleggio 11, 22100 Como, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo Mirco","family":"Abbinante","sequence":"additional","affiliation":[{"name":"Chemessentia s.r.l, Via Bovio 6, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Zambra","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienza e Alta Tecnologia e To.Sca.Lab., Universit\u00e0 dell\u2019Insubria, Via Valleggio 11, 22100 Como, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Barreca","sequence":"additional","affiliation":[{"name":"Chemessentia s.r.l, Via Bovio 6, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Zampieri","sequence":"additional","affiliation":[{"name":"Chemessentia s.r.l, Via Bovio 6, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/s42004-020-00388-9","article-title":"Open questions in organic crystal polymorphism","volume":"3","author":"Feeder","year":"2020","journal-title":"Commun. 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