Stable and Inert Mn(II)-Based and pH-Responsive Contrast Agents

Abstract

Smart/intelligent contrast agent candidates for MRI based on Mn(II) ion are rare, as it usually forms labile complexes with polyaminocarboxylate-type ligands. Here, we report the first example of a Mn(II) complex that can be activated by changing the pH of its local environment. The PC2A-EA ligand with an ethylamine pendant arm was found to form a thermodynamically stable (log <i>K</i>_MnL = 19.01, pMn = 9.27) and kinetically inert complex with Mn(II) with respect to <i>trans</i>-chelation with a metal ion such as Cu(II). The [MnH(PCA2-EA)] complex displays a relatively slow water exchange rate ((4.0 ± 0.2) × 10⁷ s^-1), but the pH-dependent coordination of the ethylamine moiety occurs in the pH range of 6-8 (log <i>K</i>_MnL^H = 6.88), enabling the complex to exhibit pH-sensitive relaxivity in the biologically relevant pH range.