Garcia, J. (2021). Synthesis and Characterization of Pyridine Derived Mn(II)-Based MRI Contrast Agents. Retrieved from https://doi.org/10.14418/wes01.2.303
The characterized protonation state of two pyridine-derived ligands, 6-((bis(pyridin-2-ylmethyl)amino)methyl)picolinic acid (TPAMA) and tris(pyridin-2-ylmethyl)amine (TPA) is reported. The synthesis for TPAMA is reported following modified literature procedures. Similar to TPA, the TPAMA ligand consists of a tertiary amine and three pyridine rings. However, one of the pyridine rings is substituted with a carboxylate arm. The Mn(II) complexes of these ligands are reported and characterized for potential use as MRI contrast agents. Potentiometric titration is used to determine the speciation in solution of the ligands and complexes in aqueous electrolyte at a physiological temperature of 37ᵒC. The pKa values of the ligands and stability constants for the complexes are also extracted by fitting the potentiometric data. The hydration state and the thermodynamic properties of the complexes are studied by temperature-dependent 17O NMR relaxometry. The potential of the complexes as contrast agents is explored by measuring the 1H longitudinal relaxation time in a pH-dependent relaxometry study. The r1 values for the complexes at physiological pH and temperature are 4.03 mM-1sec-1 for [Mn(TPA)(H2O)2]2+ and 2.12 mM-1sec-1 for [Mn(TPAMA)(H2O)]+. Additionally, the synthesis of TPADA and TPATA is reported following modified literature procedures.