Linkage Isomerization in Heme−NOx Compounds: Understanding NO, Nitrite, and Hyponitrite Interactions with Iron Porphyrins

Abstract

Nitric oxide (NO) and its derivatives such as nitrite and hyponitrite are biologically important species of relevance to human health. Much of their physiological relevance stems from their interactions with the iron centers in heme proteins. The chemical reactivities displayed by the heme-NOx species (NOx = NO, nitrite, hyponitrite) are a function of the binding modes of the NOx ligands. Hence, an understanding of the types of binding modes extant in heme-NOx compounds is important if we are to unravel the inherent chemical properties of these NOx metabolites. In this Forum article, the experimentally characterized linkage isomers of heme-NOx models and proteins are presented and reviewed. Nitrosyl linkage isomers of synthetic Fe and Ru porphyrins have been generated by photolysis at low temperatures and characterized by spectroscopy and DFT calculations. Nitrite linkage isomers in synthetic metalloporphyrin derivatives have been generated from photolysis experiments and in low-temperature matrices. In the case of nitrite adducts of heme proteins, both N-binding and O-binding have been determined crystallographically, and the role of the distal Hbonding residue in myoglobin in directing the O-binding mode of nitrite has been explored using mutagenesis. To date, only one synthetic metalloporphyrin complex containing a hyponitrite ligand (displaying an O-binding mode) has been characterized by crystallography. This is contrasted with other hyponitrite binding modes experimentally determined for coordination compounds and computationally for NO reductase enzymes. Although linkage isomerism in heme-NOx derivatives is still in its infancy, opportunities now exist for a detailed exploration of the existence and stabilities of the metastable states in both heme models and heme proteins.

Review: Recent advances in the investigations of NO activation on cobalt and manganese porphyrins: a brief review

“…The possibility of occurrence of such a transformation was previously discussed on ruthenium porphyrins by Fomitchev et al [43]. It appears from this work as well as from subsequent reports by Silaghi-Dumitrescu [44,45], Xu [46], Hoshino [47] and Kudrik [48,49] that this effect is controlled by metal identity, oxidation state and the macrocycle. As …”

“…All products of reactions were identified and confirmed by 17 quite typical for heme models and proteins [75]. [46] and previously announced by Hoshino [47]. The N-binding species, Mn(TPP)(NO 2 ), can appear as an intermediate in Mn III (TPP)(ONO) recovery after its photoinduced dissociation in degassed toluene [46,47].…”

“…Preferences of Co(III) with respect to the donor are retained in case of modifications of the macrocyclic ligand, as proved for both natural and synthetic complexes [46,51].…”

Addition and Redox Reactivity of Hydrogen Sulfides (H2S/HS−) with Nitroprusside: New Chemistry of Nitrososulfide Ligands

“…The detailed methodologies have been reported elsewhere. [59,60] The final N-containing products, N 2 , NO, N 2 O and NH 3 were identified and quantitatively assayed after a 20 h reaction time period. The relative intensities of the ions N 2 O + and NO + , at m/z 44 and 30 amu, were calibrated by using genuine N 2 O.…”

Reproducing kernel potential energy surfaces in biomolecular simulations: Nitric oxide binding to myoglobin

“…The converged energies differ by 18.5 kcal/mol and establish that both conformational isomers also exist with this functional. Experimentally, the existence of an Fe-ON state has been found for model systems, 56,58,59 but not for NO in Mb.…”