Magnetic anisotropy dynamics of paramagnetic MRI contrast agents in solution

Abstract

In magnetic resonance imaging (MRI) research, the use of paramagnetic compounds as nuclear magnetic resonance (NMR) contrast agents is growing rapidly. The PARASHIFT compound can enhance the MRI imaging and obtain additional information from the same scan, such as pH and temperature. The paramagnetic centre acts as additional magnetic force to the applied magnetic field in MRI and NMR, causing NMR peak broadening and shifting. This research focuses on pseudocontact shift (PCS)(dipolar) part of the paramagnetic NMR, as the contact shift in Lanthanide compounds is negligible due to their contracted 4f orbitals. In addition to performing relatively long ab initio molecular dynamic (AIMD) calculations on this type of compound, we present three reports that aim to improve our understanding of paramagnetic MRI contrast agent behaviour in general. In our work, find that the PCS of lanthanides molecules changes rapidly on small time scale (10 ps). Furthermore, the behaviour varies depending on the type of solvent. Our studies in the gas phase have shown that different geometries and numbers of ligands can be distinguished by calculating the paramagnetic NMR shift.In paper one we investigated the changes in geometry (axiality) on a very small timescale In a Gd-based contrast agent and how this relates to PCS. By measure the average 1H-NMR PCS, we found that this molecule is extremely flexible, with geometry fluctuation is correlated to the 1H-NMR PCS oscillations. In paper two we tested paramagnetic NMR shift and PCS of a various Lanthanides complexes. The aim was to assign the correct structural characterisation to support the experimental NMR results. Finally, in Paper Three, we aimed to use the structures from paper one to test the linear vibronic coupling model’s ability to accurately predict Crystal field Hamiltonian matrices, among other data like spin-orbit coupling energy crystal field parameter, for several consecutive AIMD structures. The calculated difference of Crystal field Hamiltonian suggests an acceptable level of accuracy, laying the groundwork for determining electron spin relaxation time (T1e), this is an unexplored area of research in the literature.

Date of Award	6 Jan 2025
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Louise Natrajan (Supervisor) & Nicholas Chilton (Supervisor)