New contrast agents alternative to those based on gadolinium

Abstract

The main objective of this doctoral thesis is the development of new systems based on transition metal ions with both high thermodynamic stability and kinetic inertness, that may be used in Magnetic Resonance lmaging (MRI) as an alternative to commercial gadolinium-based contrast agents. As a first approximation, a detailed literature revision of the stability constants of Gd3+ and Mn2+ complexes has been carried out, allowing the development of empirical expressions capable of predicting the stability constants of the complexes, as well as the corresponding pM value at pH = 7.4. Next, new Mn+2 metal complexes based on acyclic systems (rigidified H4PDTA analogues) or a macrocyclic one (triazacyclononane platform, TACN) have been prepared and fully characterized. Finally, an in vitro study of their ability to act as contrast agents supported by computational studies (DFT and CASSCF /NEVPT2) have also been performed. These studies have made it possible to obtain structural information about their behavior in solution, as well as a better understanding at the molecular level, on the mechanisms that modulate their response as contrast agents in MRI.