How does cyanide inhibit superoxide reductase? Insight from synthetic FeN4S model complexes

and CN2 have been shown to bind to the catalytic iron site of SOR, and cyanide acts as an inhibitor. To understand how these exogenous ligands alter the physical and reactivity properties of the SOR iron site, acetate-, azide-, and cyanide-ligated synthetic models of SOR have been prepared. The x-ray crystal structures of azideligated [Fe(SN4(tren))(N3)] (3), dimeric cyanide-bridged ([Fe(SN4(tren))]2-m-CN) (5), and acetate-ligated [Fe(SN4(tren))(OAc)]1 (6) are described, in addition to x-ray absorption spectrum-derived and preliminary crystallographic structures of cyanide-ligated [Fe(SN4(tren))(CN)] (4). Cyanide coordination to our model (4) causes the redox potential to shift anodically by 470 mV relative to acetate-ligated 6 and 395 mV relative to azideligated 3. If cyanide coordination were to cause a similar shift in redox potential with SOR, then the reduction potential of the catalytically active Fe31 center would fall well below that of its biological reductants. These results suggest therefore that cyanide inhibits SOR activity by making the Fe21 state inaccessible and thus preventing the enzyme from turning over. Cyanide inhibits activity in the metalloenzyme superoxide dismutase via a similar mechanism. The reduced five-coordinate precursor to 3, 4, and 6 [Fe(SN4(tren))] (1) was previously shown by us to react with superoxide to afford H2O2 via an [Fe(SN4(tren))(OOH)] intermediate. Cyanide and azide do not bind to 1 and do not prevent 1 from reducing superoxide.