Myelography Iodinated Contrast Media. I. Unraveling the Atropisomerism Properties in Solution

被引：4

作者：

Fontanive, Luca ^{[1
]}

D'Amelio, Nicola ^{[2
]}

Cesaro, Attilio ^{[1
,3
]}

Gamini, Amelia ^{[4
]}

Tavagnacco, Letizia ^{[1
,5
]}

Paolantoni, Marco ^{[6
]}

Brady, John W. ^{[5
]}

Maiocchi, Alessandro ^{[7
]}

Uggeri, Fulvio ^{[7
]}

机构：

[1] Univ Trieste, Dept Chem & Pharmaceut Sci, Lab Phys & Macromol Chem, I-34127 Trieste, Italy

[2] Bracco Imaging SpA CRB Trieste, I-34012 Trieste, Italy

[3] Elettra Sincrotrone Trieste, I-34149 Trieste, Italy

[4] Univ Trieste, Dept Life Sci, I-34127 Trieste, Italy

[5] Cornell Univ, Dept Food Sci, Ithaca, NY 14853 USA

[6] Univ Perugia, Dept Chem Biol & Biotechnol, I-06123 Perugia, Italy

[7] Bracco Imaging SpA, Ctr Ric Bracco, I-10010 Colleretto Giacosa, TO, Italy

来源：

MOLECULAR PHARMACEUTICS | 2015年 / 12卷 / 06期

关键词：

iodinated contrast media; atropisomerism; conformational analysis; NMR; IR; MM; MOLECULAR-DYNAMICS; DRUG DISCOVERY; CHEMISTRY; IOPAMIDOL; IOMEPROL; PROTEINS; SYSTEMS; ENERGY; AGENTS; PHASE;

D O I：

10.1021/mp5007486

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The present work reports a thorough conformational analysis of iodinated contrast media: iomeprol, iopamidol (the world's most utilized contrast agent), and iopromide. Its main aim is the understanding of the complex structural features of these atropisomeric molecules, characterized by the presence of many conformers with hindered rotations, and of the role of atropisomerism in the physicochemical properties of their aqueous solutions. The problem was tackled by using an extensive analysis of C-13 NMR data on the solutions of whole molecules and of simple precursors in addition to FT-IR investigation and molecular simulations. This analysis demonstrated that out of the many possible atropisomers, only a few are significantly populated, and their relative population is provided. The conformational analysis also indicated that the presence of a sterically hindered amidic bond, allowing a significant population of cis forms (E in iopromide and exo in iomeprol), may be the basis for an increased thermodynamic solubility of concentrated solutions of iomeprol.

引用

页码：1939 / 1950

页数：12

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