The Reactivity ofN-Coordinated Amides in Metallopeptide Frameworks: Molecular Events in Metal-Induced Pathogenic Pathways?

The amino acid derived tertiary amide ligand tert-butoxycarbonyl-(S)-alanine-N,N-bis(picolyl)amide (Boc-(S)-Ala-bpa, 1) has been synthesized as a model for metal-coordinating peptide frameworks. Its reactions with copper(II) and cadmium(II) salts have been studied. Binding of Cu2+ results in amide bond cleavage and formation of [(bpa)(solvent)Cu]2+ complexes. In contrast, the stable, eight-coordinate complex [(Boc-(S)-Ala-bpa)Cd(NO3)2] (5) has been isolated and characterized by X-ray crystallography. An unusual tertiary amide nitrogen coordination is observed in 5; this gives rise to significantly reduced cis-trans isomerization barriers. Possible implications for metal-induced conformational changes in proteins are discussed.