Computation of the Solvent-Accessible Surface Area of Monomer Nonionic Contrast MediaConsequences for Used Probe Radius in the Study of Hydrophilic Characteristics

摘要

RATIONALE AND OBJECTIVESThe solvent-accessible surface areas of different monomer nonionic contrast media were calculated for different probe radii. By correlating these areas with an experimental (octanol/water partition coefficient) and a calculated parameter (COMB-C), implications for the radius of the probe volume are pointed out.METHODSThe solvent-accessible surface areas of seven monomer nonionic iodinated contrast media were calculated with GEPOL (a program able to calculate various molecular surfaces and volumes) for a wide range of probe radii of the solvent. These areas were correlated with the octanol/water partition coefficient and COMB-C, a parameter describing the spatial distribution of the hydrophilic elements of a molecule.RESULTSThe correlation coefficients of the solvent-accessible surface areas (determined with the different probe radii) with the octanol/water partition coefficient and of the solvent-accessible surface areas (determined with the same probe radii) with COMB-C were good. This correlation was better for probe radii of 3 Aring; or more.CONCLUSIONSCOMB-C, a parameter designed earlier, correlated well with the hydrophilia of a monomer nonionic contrast molecule. It was shown that a probe radius of at least 3 Aring; should be used when correlations with hydrophilic characteristics are studied, rather than a probe radius of 1.5 Aring;, which is generally used in assessment of solubilities of molecules in biologic environment. Implications are discussed.