Ligand Exchange Effects on Relaxivity Profiles of Mn(II) Complexes of Polydentate Ligands

Magnetic Resonance Imaging (MRI) is a powerful technique for non-invasively visualizing internal tissue, and the diagnostic sensitivity of MRI is greatly improved through the use of a contrast agent (CA). Commercial CAs are typically complex ions formed between paramagnetic transition metal or lanthanide ions and polydentate, chelating ligands, often polyaminocarboxylates. The most commonly used commercial CAs are small-molecule Gd(III)-based complexes. Recently, however, the potential toxicity of Gd(III)-based CAs to patients with renal insufficiencies has been reported. The reported toxicity of Gd(III)-based CAs has led to a growing interest in other potential CAs. Among the most intriguing alternatives are Mn(II)-based CAs, due to their high electronic spin, long electronic relaxation times, and large hyperfine coupling constants. It has long been assumed that the relaxation rate of solvent molecules in a solution with a paramagnetic complex increases linearly with increasing concentration of the complex, and with increasing concentration of free metal ion in solution. However, it has previously been demonstrated that the relaxation rate as a function of free metal ion concentration for several Mn(II)-based complexes deviates significantly from this linear prediction. Two hypotheses were developed to explain this deviation: a fast rate of exchange between free and complexed metal ion, and an exchange mechanism dependent on the free ligand concentration. In this work, we have attempted to provide a theoretical and mathematical rationalization for the observed deviation, by deriving novel equations for the relaxation rate as a function of the free metal ion concentration that are more comprehensive than the previous equations. We succeeded in deriving an approximate equation for the relaxation rate as a function of free metal ion concentration, that differs in form from the previously assumed equation. However, using our equation, we have been unable to provide conclusive evidence supporting the idea that the deviation is due to a fast rate of ligand exchange or a ligand concentration-dependent mechanism. In an effort to better inform our modeling, as well as to determine if a fast rate of ligand exchange is a plausible explanation for the deviation, we have also attempted to measure the rates of ligand exchange for the complexes that have been shown to exhibit the deviation. While it was possible to refine the technique to the point where previously reported data on a [Cu(en)2]2+ system could be reproduced, the Mn(II) complexes of interest are significantly more complicated systems, and pose a challenge when it comes to measuring rates of ligand exchange.