Solution and Structural Investigations of Ligand Preorganization in Trivalent Lanthanide Complexes of Bicyclic Malonamides

Abstract

This report describes an investigation into the coordination chemistry of trivalent lanthanides in solution and the solid state with acyclic and preorganized bicyclic malonamide ligands. Two experimental investigations were performed: solution binding affinities were determined through single-phase spectrophotometric titrations and the extent of conformational change upon binding was investigated with single-crystal X-ray crystallography. Both experimental methods compare the bicyclic malonamide (BMA), which is designed to be preorganized for binding trivalent lanthanides, to an analogous acyclic malonamide. Results from the spectrophotometric titrations indicate that BMA exhibits a 10-100x increase in binding affinity to Ln(III) over acyclic malonamide. In addition, BMA forms compounds with high ligand-metal ratios, even when competing with water and nitrate ligands for binding sites. The crystal structures exhibit no significant differences in the nature of the binding between Ln(III) and the BMA or acyclic malonamide. These results support the conclusion that rational ligand design can lead to compounds that enhance the binding affinities within a ligand class.

Coordination of Trivalent Lanthanides with Bismalonamide Ligands: Implications for Liquid–Liquid Extraction

“…Homologous ligands with shorter alkyl groups are used instead for crystallography research, since it is argued that they form complexes with an equal coordination environment of a metal. For instance, different‐length alkyl groups in N ‐tetrasubstituted methylmalonamide, ethylmalonamide, and butylmalonamide do not change the coordination environment of a lanthanum(III) central ion in the respective nitrato crystal complexes.…”

Convenient Synthesis of 6,6-Bicyclic Malonamides: A New Class of Conformationally Preorganized Ligands for f-Block Ion Binding

“…Our approach to this problem derives from the premise that preorganization of the malonamide moiety into a conformation resembling that required in the metal−ligand complex will enhance the binding interaction. ,− In effect, the strain energy, which acyclic ligands 2 experience upon chelation to a metal center, is minimized in the bicyclic ligands 1 . ,− Initial studies with 1a and 1b showed large enhancements in extraction efficiencies and binding affinities for the bicyclic structures relative to the acyclic analogues, providing strong support for our initial premise. ,− …”

Elucidating the 3D structures of Al(iii)–Aβ complexes: a template free strategy based on the pre-organization hypothesis

“…in the conformational selection hypothesis), 32 , 33 de novo enzyme design, 34 – 36 metal binding to proteins, 37 cyclic peptides, 38 supramolecular chemistry, 39 and inorganic chemistry especially when dealing with multidentate ligands. 40 , 41 Although the exact contributions of pre-organization and induced effects in the binding processes are not yet clear – likely depending on the system under investigation – the former offers a possible solution to the absence of a structural template for the Al( iii )–Aβ system. Indeed, plenty of structures of the sole Aβ peptide presenting alternative conformations are available in the Protein Data Bank 42 and suitable algorithms could help in identifying those that satisfy the geometric conditions for the best arrangements of the first coordination sphere of aluminum.…”