This review summarizes recent developments in the investigation of the electronic structures, spectroscopic properties, and reactivities of ferrous and ferric heme-nitrosyls and how this relates to important biological processes. Ferrous heme-nitrosyls show interesting variations in electronic structure as a function of the different types of proximal ligands, as is evident from electron paramagnetic resonance, magnetic circular dichroism, and vibrational spectroscopy. In particular, coordination of imidazoles like histidine (His) increases the radical character on NO and, in this way, could help activate the bound NO for catalysis. Vice versa, the bound NO ligand imposes a strong sigma trans effect on the proximal His, which, in the case of soluble guanylate cyclase (sGC), the biological NO sensor protein, induces breaking of the Fe(II)-His bond and activates the protein. The possibility of sGC activation by HNO is also discussed. Finally, the properties of ferrous heme-nitrosyls with proximal cysteinate (Cys) coordination are evaluated. It has been known for some time that ferric heme-nitrosyls are intrinsically more labile than their ferrous counterparts, but the underlying reasons for this observation have not been clarified. New results show that this property relates to the presence of a low-lying excited state that is dissociative with respect to the Fe(III)-NO bond. On the other hand, the ground state of these complexes is best described as Fe(II)-NO(+), which shows a very strong Fe-NO bond, as is evident from vibrational spectroscopy. NO, therefore, is a weak ligand to ferric heme, which, at the same time, forms a strong Fe-NO bond. This is possible because the thermodynamic weakness and spectroscopic strength of the Fe-NO bond relate to the properties of different electronic states. Thiolate coordination to ferric hemes leads to a weakening of both the Fe-NO and N-O bonds as a function of the thiolate donor strength. This observation can be explained by a sigma backbond into the sigma* orbital of the Fe-N-O unit that is mediated by the thiolate sigma-donor orbital via orbital mixing. This is a new interaction in heme-nitrosyl that has not been observed before. This also induces a bending of the Fe-N-O subunit in these cases. New spectroscopic data on a corresponding model complex are included in this paper. Finally, the mechanism of NO reduction by cytochrome P450nor is elucidated based on recent density functional theory results.

This paper investigates the interaction between five-coordinate ferric hemes with bound axial imidazole ligands and nitric oxide (NO). The corresponding model complex, [Fe(TPP)(MI)(NO)](BF4) (MI = 1-methylimidazole), is studied using vibrational spectroscopy coupled to normal coordinate analysis and density functional theory (DFT) calculations. In particular, nuclear resonance vibrational spectroscopy is used to identify the Fe-N(O) stretching vibration. The results reveal the usual Fe(II)-NO(+) ground state for this complex, which is characterized by strong Fe-NO and N-O bonds, with Fe-NO and N-O force constants of 3.92 and 15.18 mdyn/A, respectively. This is related to two strong pi back-bonds between Fe(II) and NO(+). The alternative ground state, low-spin Fe(III)-NO(radical) (S = 0), is then investigated. DFT calculations show that this state exists as a stable minimum at a surprisingly low energy of only approximately 1-3 kcal/mol above the Fe(II)-NO(+) ground state. In addition, the Fe(II)-NO(+) potential energy surface (PES) crosses the low-spin Fe(III)-NO(radical) energy surface at a very small elongation (only 0.05-0.1 A) of the Fe-NO bond from the equilibrium distance. This implies that ferric heme nitrosyls with the latter ground state might exist, particularly with axial thiolate (cysteinate) coordination as observed in P450-type enzymes. Importantly, the low-spin Fe(III)-NO(radical) state has very different properties than the Fe(II)-NO(+) state. Specifically, the Fe-NO and N-O bonds are distinctively weaker, showing Fe-NO and N-O force constants of only 2.26 and 13.72 mdyn/A, respectively. The PES calculations further reveal that the thermodynamic weakness of the Fe-NO bond in ferric heme nitrosyls is an intrinsic feature that relates to the properties of the high-spin Fe(III)-NO(radical) (S = 2) state that appears at low energy and is dissociative with respect to the Fe-NO bond. Altogether, release of NO from a six-coordinate ferric heme nitrosyl requires the system to pass through at least three different electronic states, a process that is remarkably complex and also unprecedented for transition-metal nitrosyls. These findings have implications not only for heme nitrosyls but also for group-8 transition-metal(III) nitrosyls in general.