Invited Talk 21st International Conference on Biological Inorganic Chemistry 2025

Do you even own a proton? The awkward spectroscopic quirks of globin-(like) ferryls (121688)

Radu Silaghi-Dumitrescu 1
  1. Babes-Bolyai University, Cluj-Napoca, CLUJ, Romania

The structure and reactivity of ferryl centers in heme as well as in non-heme systems is generally discussed within three well-understood coordinates: (1) the highly-covalent and electronically-robust S=1 double-bonded Fe(IV)-oxo unit, (2) its occasional magnetic coupling (e.g., with a porphyrin cation radical in Compound I, or to another iron atom in binuclear non-heme enzymes) and ensuing illuminating particularities such as the two-state reactivity (TSR), and (3) its protonation in heme complexes where the axial ligand is an anionic cysteine thiolate or tyrosine phenolate. Occasional x-ray diffraction and spectroscopy reports explore situations where exceptions or additions to these coordinates can be argued. Among these are some unusually long iron-oxygen distances in some ferryl crystal structures of histidine-ligated heme proteins, and some accompanying spectroscopy data that raises the intriguing question of whether two ferryl systems with differing Fe-O distances can have (near?)-identical properties when probed spectroscopically. We discuss here such experimental data and explore the topic using, DFT, TD-DFT, QM/MM and ab initio dynamics – where in some cases exceptions to the three rules/coordinates can be argued, and in some cases new ferryl-related chemistry is uncovered (1-7).

  1. Zagrean-Tuza, C.; Padurean, L.; Lehene, M.; Branzanic, A. M. V.; Silaghi-Dumitrescu, R. Globin Ferryl Species: What Is the Nature of the Protonation Event at pH lower than 5? JBIC J. Biol. Inorg. Chem. 2024, 30 (1), 61–70
  2. Silaghi-Dumitrescu, R. The Nature of the High-Valent Complexes in the Catalytic Cycles of Hemoproteins. J. Biol. Inorg. Chem. 2004, 9 (4), 471–476. https://doi.org/DOI 10.1007/s00775-004-0543-2
  3. Lehene, M.; Zagrean-Tuza, C.; Iancu, S. D.; Cosma, S.-R.; Brânzanic, A. M. V; Silaghi-Dumitrescu, R.; Stoean, B. The Chlorite Adduct of Aquacobalamin: Contrast with Chlorite Dismutase. JBIC J. Biol. Inorg. Chem. 2025, 30 (1), 25–34
  4. Lehene, M.; Plesa, D.; Ionescu-Zinca, S.; Iancu, S. D.; Leopold, N.; Makarov, S. V; Brânzanic, A. M. V; Silaghi-Dumitrescu, R. Adduct of Aquacobalamin with Hydrogen Peroxide. Inorg. Chem. 2021, 60 (17), 12681–12684
  5. Silaghi-Dumitrescu, R.; Reeder, B. J.; Nicholls, P.; Cooper, C. E.; Wilson, M. T. Ferryl Haem Protonation Gates Peroxidatic Reactivity in Globins. Biochem. J. 2007, 403 (3), 391–395
  6. Lehene, M.; Brânzanic, A. M. V.; Silaghi-Dumitrescu, R. The Adducts of Cyano- and Aquacobalamin with Hypochlorite. JBIC J. Biol. Inorg. Chem. 2023, 28 (6), 583–589
  7. Lehene, M.; Zăgrean-Tuza, C.; Hădade, N.; Aghion, A.; Şeptelean, R.; Iancu, S. D.; Brânzanic, A. M. V.; Silaghi-Dumitrescu, R. A Complex of Cobalamin with an Organic Peroxide. New J. Chem. 2023, 47 (39), 18178–18185