Lanthanide chelates relevant for medical Magnetic Resonance Imaging (MRI): Quantum mechanical calculations of NMR and EPR parameters

• Research unit: COST
• Project number: C03.0055

Key words (English)

magnetic resonance imaging (MRI); contrast agents; magnetic resonance (NMR and NMRD); electron spin resonance (EPR); stability constants; supramolecular devices; targeting

Research programs (English)

COST-Action D18 - Lanthanide Chemistry for Diagnosis and Therapy

Short description (English)

The goal of this project is to obtain basic information on EPR and NMR parameters to allow engineering of high efficiency MRI contrast agents. Latest versions of quantum chemical programs allow calculations of NMR-and EPR-relevant parameters of heavy elements. We will evaluate hyperfine coupling constants between electron spins of GD3+ and Eu2+ and its nuclear spin as well as 17 O nuclear spin of bound water molecules. Furthermore electric field gradient tensors will be calculated on bound water oxygen to get quadrupole coupling constants important for 17 O NMR relaxation studies.

Partners and International Organizations (English)

AT, BE, CY, CZ, FI, FR, DE, EL, HU, IT, LV, NL, NO, PL, PT, RO, SK, ES, CH, UK

Abstract (English)

The development of very high relaxivity contrast agents is essential for building new organ specific or function specific contrast agents for medical Magnetic Resonance Imaging (MRI). Gd(III) based MRI contrast agents function by accelerating the relaxation of water protons in the surrounding tissue. High relaxivity can be achieved by optimizing the molecular tumbling time, the exchange rate of bound water molecules and the relaxation of the electron spin of the paramagnetic center. Very high field EPR experiments up to 240 GHz have been performed at the National High Magnetic Field Laboratory (Tallahassee, FL, USA) on solutions, frozen solutions and powders of Gd(III) complexes used as MRI contrast agents. For the first time a correlation has been established between the sign of the axial zero-field splitting parameter and the nature of the chelating ligand. Quantum chemical calculations of hyperfine interactions between the 7/2 Gd(III)-electron spin and 17O- and 1H nuclear spins of bound water molecules lead to isotropic hyperfine coupling constants between the electron spin (S) and the nuclear spins (I) which in very good agreement with experimental results. From the anisotropic part of the hyperfine coupling it was found that the currently used point dipole approximation for calculation of dipolar interactions between electron spin and 17O nuclear spin overestimates the effective distance for the interaction. Molecular tumbling times are best obtained from longitudinal 17O NMR relaxation rates if the corresponding quadrupole coupling constants for water molecules directly bound to Gd(III) ions are known. From DFT calculations on snapshots from trajectories obtained from classical and Car-Parinello MD simulations we calculated quadrupole coupling constants. Surprisingly, the conclusion of our calculations was that the 17O quadrupole coupling parameters of water molecules coordinated to closed shell and lanthanide metal ions are similar to those of water molecules in the bulk liquid.

References in databases (English)

Swiss Database: COST-DB of the State Secretariat for Education and Research Hallwylstrasse 4 CH-3003 Berne, Switzerland Tel. [phone] Swiss Project-Number: C03.0055