MOLECULAR AND CRYSTAL-STRUCTURE OF IODIXANOL, A NEW X-RAY CONTRAST AGENT

iodo-N,N'-(2-hydroxypropane-1,3-diyl)diacetanilide monohydrate, iodixa nol, C35H44I6N6O15. H2O, M(w)=1568.21 g mol(-1), crystallizes in the t riclinic space group P (1) over bar, Z=4 with unit cell dimensions a=1 6.864(3), b=18.164(3), c=19.360(4) Angstrom, alpha=95.68(2), beta=102. 43(2), gamma=114.56(1)degrees and V=5147(2) Angstrom(3). R=0.068 for 4 380 unique reflections. The X-ray single-crystal structure of the cont rast agent iodixanol has been determined by direct methods and differe nce Fourier syntheses. The asymmetric unit contains two stereoisomers (I and II) of iodixanol. The molecule consists of two triiodinated ben zene rings with two mono-N-alkyl substituted amide side chains on each of the rings, which are further interconnected by a bridging group: - N-C-C-C-N-. The torsional angles of the bridging group are different i n stereoisomers I and II, the angles being (from left to right) in I: -84(3)degrees, 178(4)degrees, -80(3)degrees, -88(3)degrees and in II: -90(3)degrees, 177(3)degrees, -166(4)degrees and -93(4)degrees. The di fference in torsional angles for the two stereoisomers reflects the fo lded conformation of molecule I, caused by the two intramolecular hydr ogen bonds of 3.1(2) Angstrom and 2.91(3)degrees Angstrom between O-H ... O and N-H ... O groups of the mono-N-alkyl substituted amide side chains, in contrast with the single intramolecular hydrogen bond of 3. 02(4) Angstrom between O-H ... O in the bridge in stereoisomer II.All mono-N-alkyl substituted amide side chains are tuans-related with resp ect to the ring plane. Stereoisomer I has an endo, exo configuration, stereoisomer II is exo,exo (the carbonyl oxygen atoms of the acetyl gr oups in the bridge pointing towards the ring; endo or away from it; ex o). There is an extensive intermolecular hydrogen-bonding network. Mol ecular mechanics calculations have been performed to determine the dif ference in energy between the two stereoisomers, showing stereoisomer I to have an energy 41 kJ mol(-1) lower than stereoisomer II.