title: Solid-state NMR investigation of effect of fluorination and methylation on prednisolone conformation.
abstract: Prednisolone (Prd) is a polymorphous synthetic corticosteroid that has three crystalline forms mediated by different solvents. In this study, we have demonstrated that solid-state {(1)H}(13)C cross-polarization/magic angle spinning (CP/MAS) NMR spectroscopy is able to resolve the effects of methylation and fluorination on the conformation of the steroidal rings in Prd. Two compounds were chosen for the study, 6-α-methylprednisolone (Prd-6M) and 6-α-fluoroprednisolone (Prd-6F). The (13)C signals of Prd-6F showed primarily doublet patterns, with splittings of 40-380 Hz, indicating multiple ring conformations, whereas the (13)C signals of Prd and Prd-6M exhibited a singlet pattern, indicating a unique conformation. Using evidence from chemical shift deviation and anisotropy analysis, we have demonstrated by solid-state NMR that Prd-6F adopts two different steroidal ring conformations that are different from that of Prd-6M, and less similar to that of unsubstituted Prd.
authors.affiliation: University of the Philippines Diliman, Diliman, Quezon City 1100, Philippines; Institute of Chemistry, Academia Sinica, Nankang, Taipei 11529, Taiwan, ROC.
authors.forename: Kathleen D
authors.initials: KD
authors.lastname: Carillo
authors.affiliation: University of the Philippines Diliman, Diliman, Quezon City 1100, Philippines.
authors.forename: Susan
authors.initials: S
authors.lastname: Arco
authors.affiliation: Institute of Chemistry, Academia Sinica, Nankang, Taipei 11529, Taiwan, ROC.
authors.forename: Cheng-Chung
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Institute of Chemistry, Academia Sinica, Nankang, Taipei 11529, Taiwan, ROC. Electronic address: tzougate@gate.sinica.edu.tw.
authors.forename: Der-Lii M
authors.initials: DL
authors.lastname: Tzou
mesh_terms: D066241:Carbon-13 Magnetic Resonance Spectroscopy / Q000592:standards; D054879:Halogenation; D008745:Methylation; D008968:Molecular Conformation; D011239:Prednisolone / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy / Q000592:standards
chemical_list: D011239:Prednisolone
keywords: Fluorination; Methylation; Polymorphism; Prednisolone; Steroidal ring conformation