Force field parametrization for gadolinium complexes-based on ab initio potential energy surface calculations

The recent design of new magnetic resonance imaging (MR) contrast agents is oriented toward the synthesis of gadolinium(III) complexes with ligands presenting formally neutral (amidic or alcoholic) or anionic (phosphinic) oxygen donor atoms. This paper presents the molecular mechanics (MM) parametrization of Gd interactions with amidic, alcoholic and phosphinic oxygen donor atoms, with the aim of supporting experimental effort. The parametrization is performed on the basis of a previously developed procedure applied to the parametrization of Gd interactions with polyamino carboxylate (PAC) ligands. Within the framework of valence force fields, the parameters for Gd-ligand interactions are determined by fitting the empirical potential to the ab initio potential energy surface (PES) of [Gd . 3 . OH2](3+), [Gd . 5b . OH2](3+), and [Gd . 8a](1-). Ab initio calculations were performed at the restricted Hartree-Fock (RHF) level by using an effective core potential (ECP) that includes 4f electrons in the core, an optimized valence basis set for the metal, and the 3-21G basis set for the ligand. Sampling of the PES is performed by moving the ion into the frozen coordination cage of the ab initio optimized geometries, The energy and first derivatives, with respect to the Cartesian coordinates of the metal and donor atoms, were calculated for each generated structure. Two sets of parameters, with the electrostatic contribution turned on or off in the force fields, were determined. To test the quality of the derived parameters and their transferability to other Gd complexes, MM calculations were performed on several gadolinium complexes. The results show that both sets of parameters provide reliable molecular geometries, but it is necessary to include the electrostatic contribution in the force fields to correctly reproduce the conformational energies.