Computational Description of Alkylated Iron-Sulfur Organometallic Clusters

Richard J. Jodts, M. Wittkop, Madeline B. Ho, William E. Broderick, Joan B. Broderick, Brian M. Hoffman*, Martín A. Mosquera*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


The radical S-adenosyl methionine (SAM) enzyme superfamily has widespread roles in hydrogen atom abstraction reactions of crucial biological importance. In these enzymes, reductive cleavage of SAM bound to a [4Fe-4S]1+ cluster generates the 5′-deoxyadenosyl radical (5′-dAdo•) which ultimately abstracts an H atom from the substrate. However, overwhelming experimental evidence has surprisingly revealed an obligatory organometallic intermediate Ω exhibiting an Fe-C5′-adenosyl bond, whose properties are the target of this theoretical investigation. We report a readily applied, two-configuration version of broken symmetry DFT, denoted 2C-DFT, designed to allow the accurate description of the hyperfine coupling constants and g-tensors of an alkyl group bound to a multimetallic iron-sulfur cluster. This approach has been validated by the excellent agreement of its results both with those of multiconfigurational complete active space self-consistent field computations for a series of model complexes and with the results from electron nuclear double-resonance/electron paramagnetic resonance spectroscopic studies for the crystallographically characterized complex, M-CH3, a [4Fe-4S] cluster with a Fe-CH3 bond. The likewise excellent agreement between spectroscopic results and 2C-DFT computations for Ω confirm its identity as an organometallic complex with a bond between an Fe of the [4Fe-4S] cluster and C5′ of the deoxyadenosyl moiety, as first proposed.

Original languageEnglish (US)
Pages (from-to)13879-13887
Number of pages9
JournalJournal of the American Chemical Society
Issue number25
StatePublished - Jun 28 2023

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry
  • Catalysis
  • Colloid and Surface Chemistry


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