Molecular and crystal structure of lodixanol, a new x-ray contrast agent

3,3',5,5'-Tetrakis(2,3-dihydroxypropylcarbamoyl)-2,2',4,4',6,6' -hexaiodo-N,N'-(2-hydroxypropane-1,3-diyl)diacetanilide monohydrate, iodixanol, C35H44I6O15xH2O, Mw = 1568.21 g mol-1, crystallizes in t triclinic space group P1, Z = 4 with unit cell dimensions a 16.864(3), b = 18.164(3), c = 19.360(4) Aa, α = 95.68(2), β 102.43(2), γ = 114.56(1) deg. and V = 5147(2) Aa3. R = 0.068 for 4380 unique reflections. The X-ray single-crystal structure of the contrast agent iodixanol has been determined by direct methods and difference Fourier syntheses. The asymmetric unit contains two stereoisomers (I and II) of iodixanol. The molecule consists of two triiodinated benzene 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 in stereoisomers I and II, the angles being (from left to right) in I: -84(3) deg., 178(4) deg., -80(3) deg., -88(3) deg. and in II: -90(3) deg., 177(3) deg., -166(4) deg. and -93(4) deg. The difference in torsional angles for the two stereoisomers reflects the folded conformation of molecule I, caused by the two intramolecular hydrogen bonds of 3.1(2) A and 2.91(3) deg. A 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) Aa between O-H...O in the bridge in stereoisomer II. All mono-N-alkyl substituted amide side chains are trans-related with respect to the ring plane. Stereoisomer I has en endo, exo configuration, stereoisomer II is exo,exo (the carbonyl oxygen atoms of the acetyl groups in the bridge pointing towards the ring; endo or away from it; exo). There is an extensive intermolecular hydrogen-bonding network. Molecular mechanics calculations have been performed to determine the difference in energy between the two stereoisomers, showing stereoisomer I to have an energy 41 kJ mol-1 lower than stereoisomer II. (au)