Unprecedented Kinetic Inertness for a Mn<sup>2+</sup>‐Bispidine Chelate: A Novel Structural Entry for Mn<sup>2+</sup>‐Based Imaging Agents
Daouda Ndiaye, Maryame Sy, Agnès Pallier, Sandra Même, Isidro de Silva, Sara Lacerda, Aline Nonat, Loı̈c J. Charbonnière, Éva Tóth
Abstract
Abstract The search for more biocompatible alternatives to Gd 3+ ‐based MRI agents, and the interest in 52 Mn for PET imaging call for ligands that form inert Mn 2+ chelates. Given the labile nature of Mn 2+ , high inertness is challenging to achieve. The strongly preorganized structure of the 2,4‐pyridyl‐disubstituted bispidol ligand L 1 endows its Mn 2+ complex with exceptional kinetic inertness. Indeed, MnL 1 did not show any dissociation for 140 days in the presence of 50 equiv. of Zn 2+ (37 °C, pH 6), while recently reported potential MRI agents MnPyC3A and MnPC2A‐EA have dissociation half‐lives of 0.285 h and 54.4 h under similar conditions. In addition, the relaxivity of MnL 1 (4.28 m m −1 s −1 at 25 °C, 20 MHz) is remarkable for a monohydrated, small Mn 2+ chelate. In vivo MRI experiments in mice and determination of the tissue Mn content evidence rapid renal clearance of MnL 1 . Additionally, L 1 could be radiolabeled with 52 Mn and the complex revealed good stability in biological media.