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Controlling outer-sphere solvent reorganization energy to turn on or off the function of artificial metalloenzymes

Author

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  • Divyansh Prakash

    (University of Mississippi
    Northwestern University)

  • Suchitra Mitra

    (University of Mississippi
    Weill Cornell Medicine)

  • Simran Sony

    (University of Mississippi)

  • Morgan Murphy

    (University of Mississippi)

  • Babak Andi

    (Brookhaven National Laboratory)

  • Landon Ashley

    (University of Mississippi)

  • Pallavi Prasad

    (University of Mississippi
    Regeneron Pharmaceuticals)

  • Saumen Chakraborty

    (University of Mississippi)

Abstract

Metalloenzymes play essential roles in biology. However, unraveling how outer-sphere interactions can be predictably controlled to influence their functions remains a significant challenge. Inspired by Cu enzymes, we demonstrate how variations in the primary, secondary, and outer coordination-sphere interactions of de novo designed artificial copper proteins (ArCuPs) within trimeric (3SCC) and tetrameric (4SCC) self-assemblies—featuring a trigonal Cu(His)3 and a square pyramidal Cu(His)4(OH2) coordination—influence their catalytic and electron transfer properties. While 3SCC electrocatalyzes C-H oxidation, 4SCC does not. CuI-3SCC reacts more rapidly with H2O2 than O2, whereas 4SCC is less active. Electron transfer, reorganization energies, and extended H2O-mediated hydrogen bonding patterns provide insights into the observed reactivity differences. The inactivity of 4SCC is attributed to a significant solvent reorganization energy barrier mediated by a specific His---Glu hydrogen bond. When this hydrogen bond is disrupted, the solvent reorganization energy is reduced, and C-H peroxidation activity is restored.

Suggested Citation

  • Divyansh Prakash & Suchitra Mitra & Simran Sony & Morgan Murphy & Babak Andi & Landon Ashley & Pallavi Prasad & Saumen Chakraborty, 2025. "Controlling outer-sphere solvent reorganization energy to turn on or off the function of artificial metalloenzymes," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57904-5
    DOI: 10.1038/s41467-025-57904-5
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