Mn2+ complexes of open-chain ligands with a pyridine backbone: less donor atoms lead to higher kinetic inertness

Abstract

The kinetic inertness of Mn²⁺ complexes is an important parameter for the in vivo safety of potential MRI contrast agents. Rigidifying the ligand structure typically leads to reinforced kinetic inertness. In this context, we studied the Mn²⁺ complexes of three linear poly(amino carboxylate) ligands containing a pyridine moiety in their skeleton and bearing four (L¹, L²) or three carboxylates (L³). The thermodynamic stability constants of the complexes formed with Mn²⁺, Ca²⁺, Mg²⁺, Zn²⁺ and Cu²⁺ have been determined using pH-potentiometry, ¹H relaxometry and UV/Vis spectrophotometry and are close to those of the EDTA analogues. In contrast, and despite the presence of the pyridine in the ligand backbone, the dissociation rates of the complexes are several orders of magnitude higher than that of [Mn(EDTA)]²⁻, resulting from a very efficient dissociation pathway catalyzed by the direct attack of Cu²⁺ or Cu(OH)⁺. Due to the fewer carboxylate functions, ligand L³ is less favorable for metal-assisted dissociation and provides higher kinetic inertness for its Mn²⁺ chelate than the L¹ and L² analogues. The water exchange of the monohydrated MnL³ complex has been studied in a variable temperature ¹⁷O NMR study. The exchange rate is very high, k²⁹⁸_ex = 2.8 × 10⁹ s⁻¹, which is among the highest values reported for a Mn²⁺ complex. The NMRD profiles are typical of small molecular weight Mn²⁺ chelates (r_1p = 2.44 mM⁻¹ s⁻¹ at 25 °C and 20 MHz).