Determination of Relative Stabilities of Metal-Peptide Bonds in the Gas Phase
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Updated: Oct 19, 2025

Structure and Coordination Determination of Peptide-metal Complexes Using 1D and 2D 1H NMR
Published on: December 16, 2013
Monika Cziferszky1, Dianna Truong2, Christian G Hartinger2
1Department of Chemistry and Pharmacy, Institute of Pharmacy, University of Innsbruck, Innrain 80-82, A-6020, Innsbruck, Austria.
Abstract:
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 spectrometry-based 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 RuII , OsII , RhIII , and IrIII led to the formation of various adducts, which were subsequently studied by energy-resolved fragmentation experiments. The gas-phase stability of the metal-peptide bonds depended on the metal and the binding partner. Of the four complexes used, the OsII derivative bound strongest to Met, while RuII formed the most stable coordination bond with His. RhIII was identified as the weakest peptide binder and IrIII 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.
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