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[Balanced facial hydrophilicity of ioversol: a qualitative approach of hydrophilicity]
D Meyer1, B Bonnemain, M Dugast-Zrihen
1Laboratoire Guerbet, Aulnay-Sous-Bois.
Insights
Iodinated contrast media toxicity stems from hydrophobic interactions. Evenly distributed facial hydrophilicity in molecules like ioversol can improve biocompatibility by shielding lipophilic areas.
Area of Science:
- Pharmacology
- Medicinal Chemistry
- Biocompatibility
Background:
- Chimiotoxicity of iodinated contrast media is linked to non-specific hydrophobic interactions with biological molecules.
- Molecular lipophilicity and the accessibility of lipophilic areas influence these interactions.
- Current lipophilicity measurements need enhancement with 3D structural data for better biocompatibility prediction.
Purpose of the Study:
- To explore the concept of evenly distributed facial hydrophilicity for improving contrast media biocompatibility.
- To investigate how molecular structure influences the spatial accessibility of lipophilic areas.
- To provide a framework for designing safer polyiodinated contrast media.
Main Methods:
- Analysis of molecular structures of iodinated contrast media.
- Evaluation of lipophilicity using partition coefficients.
- Assessment of the spatial localization of hydrophilic groups on the 1,3,5-triiodobenzene core.
- Concept application to the molecular structure of ioversol.
Main Results:
- Hydrophobic interactions are a key factor in contrast media chimiotoxicity.
- Evenly distributed facial hydrophilicity can minimize access to lipophilic molecular regions.
- The tertiary anilide group in ioversol facilitates facial hydrophilic protection by positioning hydroxyl groups on each face of the benzene ring.
Conclusions:
- Improving biocompatibility of iodinated contrast media requires understanding the 3D localization of hydrophilic groups.
- The concept of evenly distributed facial hydrophilicity, exemplified by ioversol, offers a strategy to reduce chimiotoxicity.
- Designing contrast agents with enhanced facial hydrophilic protection is crucial for safer clinical applications.
Abstract:
Chimiotoxicity of iodinated contrast media is essentially due to non specific hydrophobic interactions with biologic proteins and membranes. These hydrophobic interactions depend both on the whole molecular lipophilicity and on the spatial accessibility of lipophilic molecular areas. Measurements of lipophilicity by partition coefficient, partially take into account the spatial localisation of hydrophilic groups around the lipophilic area due to the 1,3,5-triiodo-benzene. These measurements have to be completed by an accurate knowledge of the three-dimensional localisation of hydrophilic groups to improve the biocompatibility of polyiodinated contrast media. The concept of evenly distributed facial hydrophilicity aims to minimize the accessibility to lipophilic area by a localisation of hydrophilic group on each plan of the benzene ring. The molecular structure of ioversol allows to put this concept in concrete form thanks to a tertiary anilide group which imposes on one hydroxy group to be located on each face of the 1,3,5-triiodo-benzene ring, providing facial hydrophilic protection.