STRUCTURAL STUDIES OF A PARTICULATE X-RAY CONTRAST AGENT - A MULTIMETHOD APPROACH

IEEC is a new X-ray liver contrast agent which has been studied by X-r ay crystallography, NMR spectroscopy and molecular modelling. 5-acetyl amino-3(N-methylacety-2,4,6-triiodobenzene carboxylate, IEEC, C17H19I3 N2O7, M(W) = 744.06 g mol(-1), crystallizes in the orthorhombic space group P2(1)2(1)2(1), Z = 4 with unit-cell dimensions a = 10.489(3), b = 11.677(6), c = 19.466(6)Angstrom and V = 2384(1) Angstrom(3). R = 0. 051 for 2278 unique reflections. A head-to-tail intermolecular hydroge n bond N-H ... O of 2.91(2) Angstrom in the crystal structure gives th e double eater side-chain an extended conformation. The structure is d isordered, with two orientations of the N-methylacetanilido residue. T he coexistence of 12 rotational isomers due to hindered rotations arou nd the Ph-CO, Ph-N and N-CO bonds has been established by means of H-1 -NMR. The isomer composition obtained from NMR is in good agreement wi th the composition obtained from calculated molecular-mechanical energ ies for the same isomers. The two isomers found in the crystal structu re are among the four most abundant isomers. Molecular-dynamics simula tions and molecular-mechanics calculations suggest substantial flexibi lity in the double eater side-chain. In the calculated lowest-energy s tructure the ester chain is pseudo-normal to the ring as opposed to th e extended conformation found in the crystal structure. The energy dif ference between these two conformations is 7.1 kJ mol(-1).