Deliberate Design of Ligand Architecture Yields Dramatic Enhancement of Metal Ion Affinity

Abstract

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.

Using Molecular Modelling to Study Interactions Between Molecules with Biological Activity

“…Metal ion affinity is enhanced if the host molecule has a unique conformation that is optimal for complexation, that is, with all the binding sites positioned to structurally complement the metal ion [Lumetta et al, 2002].…”

Thermodynamical Criteria of the Higher Selectivity of Zirconium Oxycations over Hafnium Oxycations towards Organophosphorus Ligands: Density Functional Theoretical Investigation

“…[6] The high selectivity of dithiophosphonic acid for Am III /Cm III ions over Eu III ions has been studied by DFT. [7,8] Design concepts based on quantum mechanics (QM) were applied to a bidentate ligand to obtain a remarkable enhancement in Eu 3+ ion binding affinity [9] and calix-crown-based Csselective ionophores. [10] Here, our system of interest is very important and useful for nuclear materials such as Hf and Zr ions.…”

Design and synthesis of chelating diamide sorbents for the separation of lanthanides

“…Chelating diamides have been recognized for a number of years as being affective ligands for solvent extraction of lanthanides and actinides [41][42][43][44][45][46][47][48][49]. Tetraalkyl malonamides and succinamides have been studied in [42,43,[45][46][47].…”

“…Tetraalkyl malonamides and succinamides have been studied in [42,43,[45][46][47]. This work was subsequently followed up by work aimed at synthesizing chelating diamide ligands specifically designed for rare earth chelation by controlling the dihedral angle between the two carbonyl groups through the use of a rigid backbone [44]. Ultimately, this led to the development of rigid bicyclic diamides, tailored for the solvent extraction of rare earth cations [41,48,49].…”