Reduction Mechanisms of Anticancer Osmium(VI) Complexes Revealed by Atomic Telemetry and Theoretical Calculations

Resonant X-ray emission spectroscopy (RXES) has developed in the past decade as a powerful tool to probe the chemical state of a metal center and in situ study chemical reactions. We have used it to monitor spectral changes associated with the reduction of osmium(VI) nitrido complexes to the osmium(III) ammine state by the biologically relevant reducing agent, glutathione. RXES difference maps are consistent with the proposed DFT mechanism and the formation of two stable osmium(IV) intermediates, thereby supporting the overall pathway for the reduction of these high-valent anticancer metal complexes for which reduction by thiols within cells may be essential to the antiproliferative activity.

Automated summary

RXES has been developed as a powerful tool to study chemical reactions and probe the chemical state of metal centers. In this study, RXES was used to monitor spectral changes associated with the reduction of osmium(VI) nitrido complexes to osmium(III) ammine state by glutathione, supporting the overall pathway for the reduction of high-valent anticancer metal complexes.