Oxidative Stability and Redox Coupling in 3,4,3-LI(1,2-HOPO) <i>f</i> -Element Complexes under Acidic Conditions

3,4,3-LI(1,2-HOPO) is an octadentate hydroxypyridinone chelator that forms exceptionally stable complexes with tri- and tetravalent f-element ions and has been widely explored in radiopharmaceutical development, actinide decorporation, and metal separations. Despite a broad range of applications under highly acidic, oxidative, and radiolytic conditions, the intrinsic ligand-centered redox chemistry of 3,4,3-LI(1,2-HOPO), and the influence of metal coordination on this behavior, remain poorly defined. Here, we present the first systematic electrochemical investigation of uncoordinated 3,4,3-LI(1,2-HOPO) and its La(III), Th(IV), Zr(IV), and Ce(IV/III) complexes in acidic aqueous media. Cyclic voltammetry reveals that the free ligand undergoes a single, irreversible, pH- and protonation-state-dependent oxidation assigned to the 1-electron oxidation of the hydroxypyridinone moieties, proceeding through either an electron transfer or proton-coupled electron transfer mechanism. Coordination to redox-inactive metal ions significantly suppresses ligand oxidation, shifting oxidation potentials anodically by 0.2 to 0.5 V, depending on metal identity and speciation. Density functional theory calculations demonstrate strong sensitivity of ligand redox potentials to hydration state, coordination mode, and metal–ligand interactions. A pH-dependent reduction mechanism governed by coupled electron-transfer and protonation equilibria is evidenced in the Ce(IV/III) system, enabling clear distinction between ligand-centered and metal-centered redox processes. Notably, oxygen is determined to be the chemical oxidant responsible for the spontaneous oxidation of Ce(III), and likely Bk(III), complexes, resolving a long-standing mechanistic ambiguity. Combined, these results establish quantitative design principles for predicting ligand oxidative stability in f-element complexes, as well as a general experimental framework for disentangling their ligand- and metal-centered redox chemistry using trivalent and tetravalent f-element–3,4,3-LI(1,2-HOPO) systems as an example.