ROTATIONAL BARRIERS AND THE NUMBER OF STEREOISOMERS OF IODIXANOL, AN X-RAY CONTRAST AGENT

The diastereomeric composition of iodixanol resulting from chiral centres and hindered rotation has been elucidated by two approaches. Rotational barriers for the nine bond types in iodixanol have been calculated by molecular mechanics and semiempirical quantum mechanical methods (MOPAC) as an aid in determining which bonds contribute to the diastereomeric composition by virtue of high rotational barriers. The results of the calculations suggest that rotation around the phenyl-N bond is sufficiently high (118-140 kJ mol(-1); 28-33 kcal mol(-1)) to give rise to non-interconvertible rotamers at room temperature. In this case the diastereomeric composition of iodixanol will consist of six racemates and four meso forms, as opposed to three racemates and three meso forms if phenyl-N rotation is allowed.