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

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