Poster Presentation 21st International Conference on Biological Inorganic Chemistry 2025

Thiol Nitrosation Mediated by Ferric Nitrosyl Complexes: An Isoelectronic Approach from Model Systems for Gaining Mechanistic Insight   (#544)

Samith B Jayawardana 1 , Nicholas Suffern 1 , Collin Gabel 1 , Gayan Wijeratne 1
  1. The University of Alabama, Tuscaloosa, AL, United States

Nitrosation of thiol; substrates such as methionine is a key process in biological signaling and oxidative stress regulation, yet its precise mechanistic details remain unresolved.1 One relevant proposal is that activated heme nitrogen oxide adducts mediate the efficient nitrosation of thiolates,2 however, ferrous nitrosyls, some of the commonest heme nitrogen oxide adducts have been found to be inert toward thiol substrates.3 Nonetheless, ferric nitrosyl adducts are more reactive, posing intriguing concerns about their competency to activate thiol substrates.4 Herein we investigate a thiol nitrosation potential of ferric nitrosyl adducts prepared by an isoelectronic pathway, wherein ferrous complexes have been treated with nitrosonium (NO+). Important reaction intermediates and final products have been characterized by a variety of spectroscopic techniques, including UV-Vis, FTIR, GC-MS/ECD and 2H NMR, which reveal that the reaction landscape is profoundly influenced by the electronic properties of the iron center. Particularly, electron deficient heme iron centers exhibit slower reactivity, while electron rich centers facilitate rapid thiol reaction presumably via nitrosation. Interestingly, the starting heme ferrous complex regenerates in near quantitative yield at the end of the reaction, with the concomitant product of nitrous oxide (N2O). Precise mechanistic insights and their potential implications in analogous biological systems will be discussed in detail.

  1. Dent, M. R.; DeMartino, A. W. Nitric oxide and thiols: Chemical biology, signalling paradigms and vascular therapeutic potential. British Journal of Pharmacology, 2023,1–19.
  2. Weichsel, A.; Maes, E. M.; Andersen, J. F.; Valenzuela, J. G.; Shokhireva, T. K.; Walker, F. A.; Montfort, W. R. Heme-assisted S-nitrosation of a proximal thiolate in a nitric oxide transport protein. Proceedings of the National Academy of Sciences, 2005, 102, 594-599.
  3. Rhine, M. A.; Sanders, B. C.; Patra, A. K.; Harrop, T. C. Overview and New Insights into the Thiol Reactivity of Coordinated NO in {MNO}6/7/8 (M = Fe, Co) Complexes. Inorganic Chemistry, 2015, 54, 9351-9366.
  4. Luchsinger, B. P.; Rich, E. N.; Gow, A. J.; Williams, E. M.; Stamler, J. S.; Singel, D. J. Routes to S-nitroso-hemoglobin formation with heme redox and preferential reactivity in the beta-subunits. Proceedings of the National Academy of Sciences, 2003, 100, 461-466.