AB-INITIO INVESTIGATION OF GADOLINIUM COMPLEXES WITH POLYAMINO CARBOXYLATE LIGANDS AND FORCE-FIELDS PARAMETRIZATION OF METAL-LIGAND INTERACTIONS

The conformational properties of five gadolinium(III) complexes with p olyamino carboxylate (PAC) ligands used as magnetic resonance imaging contrast agents have been investigated by ab initio and molecular mech anics (MM) methods. Ah initio calculations were performed using an eff ective core potential (ECP) that includes 4f electrons in the core and an optimized valence basis set for the metal. To test the reliability of ECP calculations, full geometry optimizations of Gd complexes were performed at the RHF and DFT (B-LYP) levels using the 3-21G and the 6 -31G basis sets for the ligands. Comparison with experimental data sh ows that ab initio calculations provide quite accurate geometries and correct conformational energies at the RHF level. Within the framework of a valence force fields, parameters for Gd-ligand interactions were determined by fitting the empirical potential to the ab initio potent ial energy surface (PES) of the [Gd-DOTA(H2O)](-1) complex. Sampling o f the PES was performed by moving the ion into the frozen coordination cage of the ab initio optimized geometry; for each generated structur e the energy and first derivatives, with respect to the Cartesian coor dinates of the metal and donor atoms, were calculated at the RHF level using both 3-21G and 6-31G basis sets for the ligand. For each consi dered basis set, two sets of parameters, with the electrostatic contri bution turned on or off in the force fields, were determined. All the implemented sets of parameters provide reliable molecular geometries f or PAC complexes, but only sets derived including the electrostatic co ntribution correctly reproduce the observed trend of conformational en ergies.