Invited Talk 21st International Conference on Biological Inorganic Chemistry 2025

Spin State and Reactivity of Enzymatic Ferryl Intermediates in Nonheme Iron Enzymes (121981)

Yisong (Alex) Guo 1 , Jared C Paris 1 , Philip M Palacios 1 , Xiaoyun Li 2 , Sha Hu 3 , Aiwen Wen 3 , Simahudeen Bathir Jaber Sathik Rifayee 4 , Tatyana Karabencheva-Christova 4 , Christo Christov 4 , Pinghua Liu 3 , Wei-chen Chang 2
  1. Carnegie Mellon University, Pittsburgh, PENNSYLVANIA, United States
  2. Chemistry, North Carolina State University, Raleigh, North Carolina, US
  3. Chemistry, Boston University, Boston, MA, US
  4. Chemistry, Michigan Technological University, Houghton, Michigan, US

Nonheme iron enzymes have garnered strong research interests in the past decades due to their ability to catalyze a broad array of oxidative reactions to lead to regio- and stereo-selective C-H functionalization. Significant progresses have been made on the mechanistic understanding of nonheme iron enzymes containing a 2-His-1-carboxylic iron binding motif, such as iron- and 2-oxoglutarate (Fe/2OG) dependent enzymes. An high-spin (S = 2) oxoferryl (Fe(IV)=O) intermediate has been identified in Fe/2OG enzymes as the conserved intermediate for C-H activation. However,  the mechanistic understanding of nonheme iron enzymes containing different iron binding motif, such as the 3/4-His motif, is much less developed. No consensus on the reactive intermediate used in the native enzymatic reactions of these 3/4-His-Fe containing enzymes has been reached. In this talk, I will present our recent discovery of the first enzymatic S = 1 Fe(IV)=O intermediate ligated by 4-His ligand environment found in a nonheme iron enzyme that catalyzes a novel oxidative carbon-sulfur bond formation between histidine and cysteine. The implication of this discovery on how the spin state of this novel enzymatic S = 1 Fe(IV)=O intermediate affects its reactivity will be further discussed. As a comparison, I will also discuss our recent study on the electronic structure and reactivity correlation on an S = 2 Fe(IV)=O intermediate found in an Fe/2OG dependent halogenase that catalyze a stereo-selective chlorination on nucleosides.