Meyer D, Petta M, Fouchet M H, Vadel M, Schaefer M, Dugast-Zrihen M, Guillemot M
Guerbet GCA, Roissy Charles de Gaulle, France.
Acta Radiol Suppl. 1996;400:8-16.
The chemotoxicity of iodinated contrast agents is essentially related to the spatial accessibilty of lipophilic and polarizable iodine atoms. This accessibility was examined in iobitridol by HPLC and 1H- and 13C-NMR spectroscopy,taking into account both the static distribution of the hydrophilic groups around the triiodinated benzene ring and in particular the dynamic modulation of this distribution. The aim of this latter parameter is to prevent distortion of the hydrophilic sphere of nonionic agents when faced with a hydrophobic environment. Iobitridol is characterized by 2 tertiary carbamoyl substituents whose high rotation barriers (deltaG353=27.6 kcal for E/Z-rotation and deltaG345=17.3 kcal for syn/anti-rotation) stabilize the hydrophilic sphere. The 3rd dihydroxylated anilide substituent does not undergo SMILES rearrangement and provides iobitridol with its even hydrophilic distribution. Iobitridol presents remarkable chemical solubility (>140% m/v) and stability. The iobitridol molecule was specifically designed with the aim of stabilizing the hydrophilic sphere around the triiodinated benzene ring, therefore permanently masking access to the iodine atoms. This new concept represents a further step forward towards the synthesis of new iodinated contrast agents which should be totally inert vis-a-vis biological membranes and proteins.
碘化造影剂的化学毒性本质上与亲脂性和可极化碘原子的空间可及性有关。通过高效液相色谱法（HPLC）以及1H-和13C-核磁共振光谱法，在碘比醇中对这种可及性进行了研究，同时考虑了三碘化苯环周围亲水基团的静态分布，特别是这种分布的动态调节。后一个参数的目的是在面对疏水环境时防止非离子型造影剂亲水球的变形。碘比醇的特征是有2个叔氨基甲酰基取代基，其高旋转势垒（E/Z旋转的ΔG353 = 27.6千卡，顺式/反式旋转的ΔG345 = 17.3千卡）稳定了亲水球。第3个二羟基化的苯胺取代基不发生SMILES重排，并为碘比醇提供了均匀的亲水分布。碘比醇具有显著的化学溶解度（>140% m/v）和稳定性。碘比醇分子经过特殊设计，目的是稳定三碘化苯环周围的亲水球，从而永久屏蔽碘原子的可及性。这一新概念代表了在合成新型碘化造影剂方面向前迈出的又一步，这些造影剂相对于生物膜和蛋白质应该是完全惰性的。
