Repurposing a peptide antibiotic as a catalyst: a multicopper-daptomycin complex as a cooperative O-O bond formation and activation catalyst

In naturally occurring metalloenzymes, cooperative multimetallic sites activate, cleave, and form dioxygen bonds. Thus, molecular scaffolds providing multimetallic sites are increasingly being exploited to develop cooperative redox catalysts. Herein, we report a multicopper complex based on a peptide antibiotic, daptomycin (dap), which mediates O-O bond formation and activation reactions. In alkaline media, UV-vis and electron paramagnetic resonance (EPR) spectroscopy showed that dap stabilized up to four Cu(ii) ions (Cu-n-dap, n = 1-4) in a square planar Cu-N-4 geometry, with an axially bound H2O or OH ligand. Cooperative rate enhancement was observed for the O-2 activation, H2O2 disproportionation, and O-2 evolution reactions, only in the presence of the multimetallic Cu complex. In situ Raman spectroscopy was used to study the intermediate species involved in the electrochemical O-2 evolution reaction and understand the catalytic mechanism behind the O-O bond formation. The observed Cu-O species related to the Cu2O2 core suggested a possible radical coupling pathway for the O-O bond formation. This study provides a strategy to repurpose natural calcium-binding peptide antibiotics as ligands, to create multimetallic sites for cooperative catalysis.