Deliberate design of ligand architecture yields dramatic enhancement of metal ion affinity

Evaluation of the malonamide substructure with respect to binding site preorganization and complementarity for lanthanide metal ions suggests a new ligand architecture specifically designed to enhance lanthanide ion affinity. Consideration of conformational reorganization, restricted bond rotation, and donor group orientation suggests that typical malonamide structures, for example, N,N,N'N'-tetrahexylpropane-1,3-diamide (1), N,N'-dibutyl-N,N'-dimethyl-2-tetradecylpropane-1,3-diamide (2), or N,N,N'N'-tetramethylpropane-1,3-diamide (6), are poorly organized for metal ion complexation. Molecular mechanics analyses show that the unfavorable enthalpic and entropic terms are eliminated by the use of the novel bicyclic architecture found in 3,9-diaza-3,9-dimethylbicyclo[4.4.0]decane-2,10-dione (7). Diamide 7 was prepared, and the X-ray crystal structure of the complex [Eu(7)(2)(NO(3))(3)] exhibits the same chelate conformation predicted by the molecular mechanics model. A hydrophobic derivative, 3,9-diaza-3,9-dioctylbicyclo[4.4.0]decane-2,10-dione (8), was prepared, and solvent extraction studies reveal that the preorganized architecture of 8 gives a dramatic enhancement in binding affinity, exhibiting Eu(3+) distribution coefficients that are 7 orders of magnitude larger than a typical malonamide ligand, 1.