The capacious and rigid mausolate ligand 1 2− has the capacity to adaptively coordinate some of the largest metal cations on the periodic table, such as those which are utilized in targeted alpha‐particle therapy. One such ion, Ra 2+ , has proven challenging to keep securely contained by other chelators. Here we investigate the binding behavior of Ba 2+ (≈96% the size of Ra 2+ but conveniently nonradioactive) with the mausolate 1 2− along with Mg 2+ , Ca 2+ , and Sr 2+ , principally utilizing real‐time electrospray ionization mass spectrometry monitoring. We also report the syntheses of several functionalized mausolate derivatives, 3–5 2− , and compare their binding abilities with previously reported variants. We find that the mausolates display a distinct preference for larger alkaline earth metals, with Ba 2+ showing extremely rapid uptake and promising stability in a number of physiologically relevant conditions. We also demonstrate a thermodynamic preference of Ba 2+ for the mausolate over some other well‐known chelators. The incorporation of a reactive bromine atom in the 4‐pyridine position of the mausolate ( 3 2− ) can be utilized to introduce further functionalization through a nucleophilic substitution pathway without compromising coordination ability.
Smart et al. (2026) studied this question.