Why copper is preferred over iron for oxygen activation and reduction in haem-copper oxidases

Ambika Bhagi-Damodaran, Matthew A. Michael, Qianhong Zhu, Julian Reed, Braddock A. Sandoval, Evan N. Mirts, Saumen Chakraborty, Pierre Moenne-Loccoz, Yong Zhang, Yi Lu

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Haem-copper oxidase (HCO) catalyses the natural reduction of oxygen to water using a haem-copper centre. Despite decades of research on HCOs, the role of non-haem metal and the reason for nature's choice of copper over other metals such as iron remains unclear. Here, we use a biosynthetic model of HCO in myoglobin that selectively binds different non-haem metals to demonstrate 30-fold and 11-fold enhancements in the oxidase activity of Cu- and Fe-bound HCO mimics, respectively, as compared with Zn-bound mimics. Detailed electrochemical, kinetic and vibrational spectroscopic studies, in tandem with theoretical density functional theory calculations, demonstrate that the non-haem metal not only donates electrons to oxygen but also activates it for efficient O-O bond cleavage. Furthermore, the higher redox potential of copper and the enhanced weakening of the O-O bond from the higher electron density in the d orbital of copper are central to its higher oxidase activity over iron. This work resolves a long-standing question in bioenergetics, and renders a chemical-biological basis for the design of future oxygen-reduction catalysts.

Original languageEnglish (US)
Pages (from-to)257-263
Number of pages7
JournalNature Chemistry
Issue number3
StatePublished - Mar 1 2017


ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

Cite this

Bhagi-Damodaran, A., Michael, M. A., Zhu, Q., Reed, J., Sandoval, B. A., Mirts, E. N., Chakraborty, S., Moenne-Loccoz, P., Zhang, Y., & Lu, Y. (2017). Why copper is preferred over iron for oxygen activation and reduction in haem-copper oxidases. Nature Chemistry, 9(3), 257-263. https://doi.org/10.1038/nchem.2643