Determination of Relative Stabilities of Metal-Peptide Bonds in the Gas Phase.

Understanding binding site preferences in biological systems as well as affinities to binding partners is a crucial aspect in metallodrug development. We here present a mass spectrometrybased method to compare relative stabilities of metal-peptide adducts in the gas phase. Angiotensin 1 and substance P were used as model peptides. Incubation with isostructural N -heterocyclic carbene (NHC) complexes of Ru II , Os II , Rh III , and Ir III led to the formation of various adducts, which were subsequently studied by energy-resolved fragmentation experiments. The gas phase stability of the metalpeptide bonds depended on the metal and the binding partner. Of the four complexes used, the Os II derivative binds strongest to Met, while Ru II forms the most stable coordination bond with His. Rh III was identified as the weakest peptide binder and Ir III formed peptide adducts with intermediate stability. Probing these intrinsic gas phase properties can help in the interpretation of biological activities and the design of site-specific protein binding metal complexes.