Poster Presentation 21st International Conference on Biological Inorganic Chemistry 2025

Harnessing Hydrogen Bonding to Control Fe/O2 Reactivity in Thiolate-ligated Nonheme Iron Complexes (#498)

Sudha Yadav 1 , Vishal Yadav 2 , Robert Lyons 1 , Zoe Readi-Brown 3 , David Goldberg 1
  1. Department of Chemistry, Johns Hopkins University, Baltimore, MD, United States
  2. Department of Chemistry, Pennsylvania State University, Pennsylvania
  3. Department of Chemistry, Caltech, Pasadena, California

 

A new tetradentate ligand, BNPAMe2SH, with two pyridyl nitrogen donors, one tertiary amine donor, and one anionic alkyl-thiolate donor was synthesized. This ligand also incorporates neopentylamino hydrogen bonding groups in the second coordination sphere. The metal complex, Fe(BNPAMe2S)(Br), reacts with O2 at low temperature (-40 °C) to give a well-defined iron superoxide (Fe-O2-•) intermediate, which was characterized by UV-vis, Mössbauer, EPR, ATR-FTIR spectroscopies, and cold-spray ionization mass spectrometry (CSIMS). Density functional theory (DFT) calculations combined with the spectroscopic data strongly suggests the formation of a “side-on” bound superoxide ligand for [Fe(BNPAMe2S)(O2-•)]. This complex is a rare example of a nonheme Fe(O2-•) species. Upon warming from -40 to 25 °C, the iron superoxide complex converts to an iron sulfinate (Fe(O2SR)) species, and mechanistic probes indicate that a singly oxygenated iron sulfenate (Fe(OSR) species is formed along the pathway to the S-dioxygenated sulfinate product. This mechanism is analogous to that proposed for the thiol dioxygenases (TDOs), which is thought to involve a thiolate-ligated iron superoxide that attacks the coordinated sulfur atom. A related complex lacking hydrogen-bonding groups, Fe(BPAMe2S)(Br), reacts with O2 to form a high-spin Fe(III)-OH species without stabilizing an Fe–O2-• intermediate or promoting S-oxygenation. These findings highlight the role of second-sphere hydrogen bonding in dictating iron/O2 reactivity, influencing the preference for S-oxygenation over hydrogen atom abstraction.

  1. Yadav S., Yadav V., Siegler, M. A., Moënne-Loccoz, P., Goldberg, D. P., “A Nonheme Iron (III) Superoxide Complex Leads to Sulfur Oxygenation”, J. Am. Chem. Soc., 2024, 146, 12, 7915-7921.
  2. Yadav S., Lyons, S. R., Brown, Z. R., Siegler, M. A., Goldberg, D. P., “Influence of the second coordination sphere on O2 activation by a nonheme iron(II) thiolate complex”, Journal of Inorganic Biochemistry, 2025, 264, 112776 .