Stabilization of the hydrophilic sphere of iobitridol, an iodinated contrast agent, as revealed by experimental and computational investigations.

PURPOSE: The regular distribution in space and the stability in time of the hydrophilic sphere surrounding iobitridol were investigated. This is a novel yet important concept in the design of polyiodinated contrast agents since such a sphere is meant to hide their hydrophobic core and thus prevent hydrophobic interactions with biomacromolecules and hence chemotoxicity.
METHODS: The methods used were experimental (HPLC, 1H- and 13C-NMR spectroscopy) and computational (calculation of conformational behavior and molecular electrostatic potentials).
RESULTS: Iobitridol exists as a mixture of stereoisomers due to hindered rotation around several bonds. High-temperature molecular dynamics established the existence between 0 and 15 kcal/mol of 238 conformers belonging to 14 classes. Most of these conformers have an inaccessible hydrophobic core, and variable temperature molecular dynamics confirmed that the hydrophilic sphere around iobitridol is stable against external disruption.
CONCLUSIONS: This study has demonstrated that iobitridol fulfils the physicochemical and structural criteria believed to render a polyiodinated contrast agent inert toward interacting with biomacromolecules.