Reactivity mechanisms, phenoxyl complexes

The BIDPhE model complex provides us with a unique opportunity to explore the reactivity of a phenoxyl radical-diiron(III) moiety with a variety of inhibitors of the R2 active site. Several studies have been carried out in which the R2 protein was treated with different radical inhibitors (52-54). The mechanism of inhibition, the oxidation products formed from the inhibitors and the possible concomitant reactivity of the diiron(III) center with these agents are all subjects of current investigation. The reactivity of the BIDPhE model complex may be more easily studied than that of R2, given the relative ease of handling a small molecule compared to a protein. 

Fig. 23. Proposed mechanisms for Tyr-Cys cofactor biogenesis. (A) Initial Cu(II) binding leads to the appearance of resonance contributions from a reactive phenoxyl that electrophilically attacks the neighboring Cys-228 thiol. (B) Cu(I) binding produces an oxygen-reactive complex that drives hydrogen abstraction from Cys-228 to form a thiyl free radical which subsequently attacks the neighboring Tyr-272 ring with formation of a carbon-sulfur covalent bond.

---