Manganese(II) Complexes as Potential Contrast Agents for MRI

Abstract

Mn2+ has five unpaired d electrons, a long electronic relaxation time, and labile water exchange, which make it an attractive alternative to Gd3+ in the design of contrast agents for medical Magnetic Resonance Imaging. In order to ensure in vivo safety and high contrast agent efficiency, the Mn2+ ion has to be chelated by a ligand that provides high thermodynamic stability and kinetic inertness of the complex and has to have at least one free coordination site for a water molecule. Unfortunately, these two requirements are contradictory, as lower denticity of the ligands, which leads to more inner‐sphere water molecules often implies a decreased stability of the complex, and, therefore, it is necessary to find a balance between both requirements. In the last decade, a large amount of experimental data has been collected to characterize the physico‐chemical properties of Mn2+ chelates with variable ligand structures. They now allow for establishing trends of how the ligand structure, the rigidity of the ligand scaffold, and its donor–acceptor properties influence the thermodynamic, kinetic, and redox stability of the Mn2+ complex. This microreview surveys the current literature in this field.

Iron(III) Contrast Agent Candidates for MRI: a Survey of the Structure–Effect Relationship in the Last 15 ­Years of Studies

“…In addition, paramagnetic ions of lanthanides are under ongoing investigation with all of their benefits of high coordination numbers and high magnetic moments. [8,9] Ordinary manganese [10][11][12] and iron, [1,13] however, have also gained advocates because of their ubiquity and endogenous character with wellknown and highly predictable physiology.…”

Multifunctional Gadolinium-Doped Manganese Carbonate Nanoparticles for Targeted MR/Fluorescence Imaging of Tiny Brain Gliomas

“…4, 5 However, the occurrence of nephrogenic systemic fibrosis (NSF) related to Gd (III) ions restricts widespread application of Gd-based contrast agents in clinical practice. 6,7 Therefore, attention has shifted to alternative agents such as manganese (Mn)-based complexes [8][9][10][11] and nanoparticles (NPs), [12][13][14][15] which has produced encouraging results for both in vitro and in vivo MR imaging of cancer. [16][17][18] For instance, MnO NPs have been successfully used for T 1 -weighted MR imaging of metastatic brain tumors.…”

Speciation of Metal Complexes of Medicinal Interest: Relationship between Solution Equilibria and Pharmaceutical Properties

“…The trivalent Gd(III) is the most efficient relaxation agent among all paramagnetic cations due to its high electron spin (S = 7/2) and slow electron spin relaxation and therefore it is the most commonly used ion in MRI as CAs. Other paramagnetic metal ions, in particular the non-toxic biocompatible Mn(II) (S = 5/2) have also been considered as MRI contrast agent and their role becomes more and more important [153]. As the free Gd(III) ion is toxic [154], it is necessary to be chelated with appropriate multidentate ligands (Chart 4), which ensure a high thermodynamic stability and/or kinetic inertness.…”