RESUMO
The search for more biocompatible alternatives to Gd3+ -based MRI agents, and the interest in 52 Mn for PET imaging call for ligands that form inert Mn2+ chelates. Given the labile nature of Mn2+ , high inertness is challenging to achieve. The strongly preorganized structure of the 2,4-pyridyl-disubstituted bispidol ligand L1 endows its Mn2+ complex with exceptional kinetic inertness. Indeed, MnL1 did not show any dissociation for 140â days in the presence of 50â equiv. of Zn2+ (37 °C, pHâ 6), while recently reported potential MRI agents MnPyC3A and MnPC2A-EA have dissociation half-lives of 0.285â h and 54.4â h under similar conditions. In addition, the relaxivity of MnL1 (4.28â mm-1 s-1 at 25 °C, 20â MHz) is remarkable for a monohydrated, small Mn2+ chelate. Inâ vivo MRI experiments in mice and determination of the tissue Mn content evidence rapid renal clearance of MnL1 . Additionally, L1 could be radiolabeled with 52 Mn and the complex revealed good stability in biological media.