Node‐Encoded Control of Lanthanide Self‐Assembly Enables Predictable and Water‐Stable Polyhedra for Bioimaging

ABSTRACT Multinuclear lanthanide‐organic polyhedra offer attractive molecular scaffolds for biomedical imaging, while their predictable construction remains challenging because the high coordination numbers and kinetic lability of lanthanide ions often compromise both topological fidelity and aqueous stability. Here, we develop a coordination‐node‐encoding strategy in which a deprotonation‐stabilized terpyridine‐bis(tetrazolate) chelate preorganizes the local lanthanide coordination environment and thereby programs subsequent self‐assembly. Systematic variation of ligand connectivity affords a family of anionic lanthanide‐organic polyhedra spanning triangular, macrocyclic, tetrahedral, and trigonal‐prismatic topologies. Structural analyses and control experiments demonstrate that cooperative pentadentate chelation coupled with deprotonation imposes the directional coordination constraints required for topology‐selective assembly, while the anionic tetrazolate‐rich surfaces enhance the hydrophilic character and aqueous compatibility of the assemblies. The Gd III truncated‐tetrahedral polyhedron exhibits a per‐Gd III longitudinal relaxivity of 27.9 mM −1 ·s −1 at 9.4 T and 298 K, approximately sevenfold higher than that of Gd‐DTPA measured under identical conditions, corresponding to a molecular relaxivity of 167.1 mM −1 ·s −1 . The Eu III analogues display characteristic red luminescence with high photoluminescence quantum yields (up to 54%) and enable low‐toxicity cellular imaging. Mixed Eu/Gd polyhedra further integrate Eu III luminescence and Gd III magnetic‐resonance contrast within a single molecular architecture, enabling luminescence and MR imaging. This work establishes coordination‐node encoding as a modular design principle for predictable lanthanide polyhedron formation and provides a versatile platform for developing multifunctional lanthanide‐based imaging systems with enhanced aqueous compatibility.