Outer-Sphere Hydrogen Bonds Amplify Mutual Actinide Separation

Abstract Mutual actinide separation is critical for nuclear waste remediation, superheavy-element production, and f-block-element-based radiopharmaceuticals, yet it remains a formidable challenge owing to the high chemical similarity of these elements and the harsh conditions typically encountered, such as high acidity and intense radioactivity. Here, we show that combining lipophilic TODGA with the histidine-decorated hydrophilic ligand Phen-2DIHis enables the efficient separation of Am(III), Cm(III), and Cf(III) under highly acidic conditions. This system provides substantially enhanced separation factors for both Am(III)/Cf(III) (383) and Cm(III)/Cf(III) (36.9) compared to benchmark methods while maintaining practical metal distributions by directing the targeted actinide ions into opposite phases. Spectroscopic titrations and slope analyses support predominant 1:1 metal–ligand complexation. Theoretical calculations further suggest that nitrate-involved outer-sphere hydrogen bonding from the histidine termini may contribute unexpectedly to the thermodynamic bias for separation processes. These results highlight weak interactions beyond the inner coordination sphere as a critical design handle for mutual actinide separation under strongly acidic conditions.