Binding of Nitric Oxide to a Synthetic Model of Iron-Containing Nitrile Hydratase (Fe-NHase) and Its Photorelease: Relevance to Photoregulation of Fe-NHase by NO

Abstract

The activity of the non-heme iron enzyme nitrile hydratase (Fe-NHase) is modulated by nitric oxide (NO). The inactive (dark form) NO-bound enzyme is activated when exposed to light via the release of NO from the iron center. In order to determine whether oxygenation of active site Fe-bound Cys-S centers are involved in this process of NO regulation, a model complex (Et(4)N)[(Cl(2)PhPepS)Fe(NO)(DMAP)] (8) has been synthesized and structurally characterized. Complex 8 does not exhibit any NO photolability. However, following oxygenation of the Fe-bound thiolato-S centers to sulfinates (with the aid of oxaziridine), the resulting complex (Et(4)N)[(Cl(2)PhPep{SO(2)}(2))Fe(NO)(DMAP)] (9) releases NO readily upon illumination with visible light. Spectroscopic properties of 8 and 9 confirm that these species do mimic the active site of Fe-NHase closely, and the results indicate that NO photolability is related to S-oxygenation. Results of density functional theory and time-dependent DFT studies on both 8 and 9 indicate that S-oxygenation weakens Fe-S bonding and that strong transitions near 470 nm transfer an electron from a carboxamido-N/sulfinato-SO(2) MO to a dpi(Fe)-pi*(NO)/d(z)2(Fe)-sigma*(NO) antibonding orbital in 9. In case of 8, strong S-Fe-NO bonding interactions prevent the release of NO upon illumination. Together, the results of this work strongly suggest that oxygenated Cys-S centers play an important role in the process of NO regulation of Fe-NHases.

Thioether-ligated iron(ii) and iron(iii)-hydroperoxo/alkylperoxo complexes with an H-bond donor in the second coordination sphere

“…1 also include a sulfur donor in the first coordination sphere, but the incorporation of sulfur or other heteroatoms in model complexes is rare. 23,[25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] In addition, little work has been done to determine the effect of secondary sphere interactions, such as hydrogen-bonding networks, on the structures and spectroscopic properties of iron-peroxo complexes, 42,43 despite their roles in many of the corresponding enzyme intermediates.…”

Reversible binding of nitric oxide to an Fe(iii) complex of a tetra-amido macrocycle

“…The strong visible and near-IR absorptions of [Fe(TAML)NO] − at 533 and 888 m, respectively, are qualitatively similar to absorptions at 565 and 970 nm recently reported for the S=1 {Fe-NO} 6 adduct of a tetra-anionic N 2 S 2 ligand scaffold from which NO could be released upon heating. 9 In the N 2 S 2 system, the near-IR absorptions were assigned to electronic transitions in the S=1 manifold, but cooling the nitrosyl to 0 °C bleached these bands owing to spin crossover from the S=1 to the S=0 spin state. To perform similar studies with [Fe(TAML)NO] − , variable temperature UV-vis experiments from −30 to 80 °C in 100:1 CH 3 CN:MeOH or 0 to −78 °C in MeOH were performed (Figure 3b,c).…”

Recent advances in multinuclear metal nitrosyl complexes

“…They were obtained by reaction of excess NO with (Et 4 N) 2 [Fe(PhPepS)(Cl)] in aprotic solvents such as MeCN and DMF as shown in Scheme 8 [91]. The photochemical properties were also investigated and relate to the photoregulation of Fe-NHase by NO [92]. …”