title: Myelography Iodinated Contrast Media. 2. Conformational Versatility of Iopamidol in the Solid State.
abstract: The phenomenon of polymorphism is of great relevance in pharmaceutics, since different polymorphs have different physicochemical properties, e.g., solubility, hence, bioavailability. Coupling diffractometric and spectroscopic experiments with thermodynamic analysis and computational work opens to a methodological approach which provides information on both structure and dynamics in the solid as well as in solution. The present work reports on the conformational changes in crystalline iopamidol, which is characterized by atropisomerism, a phenomenon that influences both the solution properties and the distinct crystal phases. The conformation of iopamidol is discussed for three different crystal phases. In the anhydrous and monohydrate crystal forms, iopamidol molecules display a syn conformation of the long branches stemming out from the triiodobenzene ring, while in the pentahydrate phase the anti conformation is found. IR and Raman spectroscopic studies carried out on the three crystal forms, jointly with quantum chemical computations, revealed that the markedly different spectral features can be specifically attributed to the different molecular conformations. Our results on the conformational versatility of iopamidol in different crystalline phases, linking structural and spectroscopic evidence for the solution state and the solid forms, provide a definite protocol for grasping the signals that can be taken as conformational markers. This is the first step for understanding the crystallization mechanism occurring in supersaturated solution of iopamidol molecules.
authors.affiliation: Laboratory of Physical and Macromolecular Chemistry, Department of Chemical and Pharmaceutical Sciences, University of Trieste , via Giorgieri 1, I-34127 Trieste, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bellich
authors.affiliation: Elettra Sincrotrone Trieste , Area Science Park, I-34149 Trieste, Italy.
authors.forename: Silvia
authors.identifier: 0000-0002-5630-9168
authors.initials: S
authors.lastname: Di Fonzo
authors.affiliation: Laboratory of Physical and Macromolecular Chemistry, Department of Chemical and Pharmaceutical Sciences, University of Trieste , via Giorgieri 1, I-34127 Trieste, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Tavagnacco
authors.affiliation: Department of Chemistry, Biology and Biotechnologies, University of Perugia , via Elce di Sotto 8, I-06123 Perugia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Paolantoni
authors.affiliation: Elettra Sincrotrone Trieste , Area Science Park, I-34149 Trieste, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Masciovecchio
authors.affiliation: Department of Science and High Technology, To.Sca.Lab and INSTM, University of Insubria , via Valleggio 11, I-22100 Como, Italy.
authors.forename: Federica
authors.identifier: 0000-0002-6001-9040
authors.initials: F
authors.lastname: Bertolotti
authors.affiliation: Laboratory of Physical and Macromolecular Chemistry, Department of Chemical and Pharmaceutical Sciences, University of Trieste , via Giorgieri 1, I-34127 Trieste, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Giannini
authors.affiliation: Laboratory of Physical and Macromolecular Chemistry, Department of Chemical and Pharmaceutical Sciences, University of Trieste , via Giorgieri 1, I-34127 Trieste, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: De Zorzi
authors.affiliation: Laboratory of Physical and Macromolecular Chemistry, Department of Chemical and Pharmaceutical Sciences, University of Trieste , via Giorgieri 1, I-34127 Trieste, Italy.
authors.forename: Silvano
authors.initials: S
authors.lastname: Geremia
authors.affiliation: Centro Ricerche Bracco, Bracco Imaging SpA , via Ribes 5, I-10010 Colleretto Giacosa, Turin, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Maiocchi
authors.affiliation: Centro Ricerche Bracco, Bracco Imaging SpA , via Ribes 5, I-10010 Colleretto Giacosa, Turin, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Uggeri
authors.affiliation: Department of Science and High Technology, To.Sca.Lab and INSTM, University of Insubria , via Valleggio 11, I-22100 Como, Italy.
authors.forename: Norberto
authors.initials: N
authors.lastname: Masciocchi
authors.affiliation: Laboratory of Physical and Macromolecular Chemistry, Department of Chemical and Pharmaceutical Sciences, University of Trieste , via Giorgieri 1, I-34127 Trieste, Italy.|Elettra Sincrotrone Trieste , Area Science Park, I-34149 Trieste, Italy.
authors.forename: Attilio
authors.identifier: 0000-0001-9939-6647
authors.initials: A
authors.lastname: Cesàro
mesh_terms: D003287:Contrast Media / Q000737:chemistry*; D003460:Crystallization / Q000379:methods; D007479:Iopamidol / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D009192:Myelography / Q000379:methods; D012995:Solubility; D012996:Solutions / Q000737:chemistry; D013059:Spectrum Analysis, Raman / Q000379:methods; D013816:Thermodynamics
chemical_list: D003287:Contrast Media; D012996:Solutions; D007479:Iopamidol
keywords: IR; Raman; XRD; conformational versatility; iopamidol; thermodynamics