A theoretical study on the reaction pathways of peroxynitrite formation and decay at nonheme iron centers

A computational study based on density functional theory was undertaken to identify possible reaction pathways for the formation and decomposition of peroxynitrite at models of the active sites of the nonheme superoxide scavenging enzymes superoxide reductase (SOR) and iron superoxide dismutase (FeSOD). Two peroxynitrite isomers and their possible protonated states were investigated, namely FeOONO − , FeN(O)OO − , FeOONOH, and FeN(O)OOH. Peroxynitrite formation at the active sites was assumed by either the interaction of a peroxynitrite cis / trans anion with the pentacoordinated iron active site or the interaction between a nitric oxide bound adduct and superoxide; both scenarios were found to be facile for all models investigated. The ferrous adducts of the FeOONO − isomer were found to undergo instant heterolytic cleavage of the OONO bond to yield nitrite, whereas for the ferric adducts, the homolytic cleavage of the OONO bond to yield nitrogen dioxide was found to be energetically facile. For the FeN(O)OO − isomer, the active site models of FeSOD and SOR were only able to accommodate the cis isomer of peroxynitrite. Ferric adducts of the cis FeOONO − isomer were found to be energetically more stable than their trans counterparts and were also more stable than the cis adducts of the FeN(O)OO − isomer; conversely, the protonated forms of all adducts of the FeOONOH isomer were found to be lower in energy than their equivalent FeN(O)OOH adducts. Multiple reaction pathways for the decomposition of the formed peroxynitrite adducts (whether the anions or the protonated forms) were proposed and explored. The energy requirements for the decomposition processes ranged from exothermic to highly demanding depending on the peroxynitrite isomer, the type of model (whether an SOR or FeSOD active site), and the oxidation state of iron. © 2014 Wiley Periodicals, Inc.