Understanding the Metastability of Theophylline FIII by Means of Low-Frequency Vibrational Spectroscopy

Autor(es)

Paiva, Eduardo Maia ^[1] ; Li, Qi ^[2] ; Zaczek, Adam J. ^[2] ; Pereira, Claudete F. ^[3] ; Rohwedder, Jarbas Jose Rodrigues ^[1] ; Zeitler, J. Axel ^[2]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, UNICAMP, Inst Chem, BR-13083862 Campinas, SP - Brazil

^[2] Univ Cambridge, Dept Chem Engn & Biotechnol, Cambridge CB3 0AS - England

^[3] Univ Fed Pernambuco, Dept Fundamental Chem, BR-50740560 Recife, PE - Brazil

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR PHARMACEUTICS; v. 18, n. 9, p. 3578-3587, SEP 6 2021.
• Citações Web of Science: 0

Resumo

While theophylline has been extensively studied with multiple polymorphs discovered, there is still currently no conclusive structure for the metastable theophylline form III. In this present work, by combining more widely used techniques such as X-ray diffraction and thermogravimetric analysis with more emerging techniques like low-frequency Raman and terahertz time-domain spectroscopy, to analyze the structure and dynamics of a crystalline system, it was possible to provide further evidence that the form III structure has a theophylline monohydrate structure with the water molecules removed. Solid-state density functional theory simulations were paramount in proving that this proposed structure is correct and explain how vibrational modes within the crystal structures feature and govern polymorphic transitions and the metastable form III. Through the insight provided by both simulated and experimental results, it was possible to decisively conclude the elusive crystal structure of theophylline form III. It was also shown that the correct space group for theophylline monohydrate is not P21/n but, in fact, Pc. (AU)

• Processo FAPESP: 14/50951-4 - INCT 2014: Tecnologias Analíticas Avançadas
• Beneficiário: Celio Pasquini
• Modalidade de apoio: Auxílio à Pesquisa - Temático