COMPUTATIONAL EXPLORATION OF STRUCTURE PROPERTY RELATIONSHIPS FOR MRI CONTRAST AGENTS
Rafael de la Flor1, Christopher Collins2, Maria Benavides1, David Yaron2.
1University of Houston-Downtown, Houston, TX, 2Carnegie-Mellon University, Pittsburgh, PA.
Magnetic resonance imaging uses chemical compounds called contrast agents in vivo to enhance images of the human body. An especially successful class of contrast agents, known as GCBAs, include the toxic lanthanide metal ion gadolinium(III) and currently make up all of the 9 FDA approved contrast agents in common use. A variety of alternative metals have the potential to be used as contrast agents. Use of such metals requires development of ligands that can bind to all but one binding site of the metal ion, leaving the remaining site to reversibly bind water molecules. The goal of this project is to use quantum chemical computations to explore the structure-property relationships for such MRI contrast agents based on Mn(II) and Cr(II) in combination with DTPA. and EDTA. The initial focus is on the stability of the metal-ligand complexes, since the metals are toxic if they become unbound from the ligand. Computationally efficient semi-empirical quantum chemical methods are used to allow studies to be carried out across a wide range of complexes. Comparison with higher-level density functional theory methods (DFT) on MnDTPA/MnEDTA using BYL3P functional and basis sets 6-31G and 6-31G + is used to estimate the reliability of the semi-empirical approaches.