A Gadolinium‐Binding Cyclodecapeptide with a Large High‐Field Relaxivity Involving Second‐Sphere Water

Abstract

Abstract A new cyclodecapeptide incorporating two prolylglycine sequences as β‐turn inducers and bearing four side chains with acidic carboxyl groups for cation complexation has been prepared. Structural analysis in water by 1 H NMR spectroscopy and CD shows that this template adopts a conformation suitable for the complexation of lanthanide ions Ln 3+ , with its carboxyl groups oriented on the same face of the peptide scaffold. Luminescence titrations show that mononuclear Ln–PA complexes are formed with apparent stability constants of log β 110 ≈6.5 (pH 7). The high‐field water relaxivity values arising from the Gd–PA complex at 200–500 MHz have been interpreted with molecular parameters determined independently. The experimentally determined water relaxivities are undoubtedly 30 % higher than the expected values for this complex with two inner‐sphere (IS) water molecules and a medium‐range rotational correlation time ( τ R =386 ps (±10 %)). This led us to propose the existence of a large second‐sphere (2S) contribution to the relaxivity caused by the interaction of water molecules with the hydrophilic peptide ligand by hydrogen‐bonding.