Nitrogen Oxide Atom-Transfer Redox Chemistry; Mechanism of NO_(g) to Nitrite Conversion Utilizing μ-oxo Heme-Fe^III–O–Cu^II(L) Constructs

Abstract

While nitric oxide (NO, nitrogen monoxide) is a critically important signaling agent, its cellular concentrations must be tightly controlled, generally through its oxidative conversion to nitrite (NO2−) where it is held in reserve to be reconverted as needed. In part, this reaction is mediated by the binuclear heme a3/CuB active site of cytochrome c oxidase. In this report, the oxidation of NO(g) to nitrite is shown to occur efficiently in new synthetic µ-oxo heme-FeIII−O−CuII(L) constructs (L being a tridentate or tetradentate pyridyl/alkylamino ligand), and spectroscopic and kinetic investigations provide detailed mechanistic insights. Two new X-ray structures of µ-oxo complexes have been determined and compared to literature analogs. All µ-oxo complexes react with 2 mol equiv NO(g) to give 1:1 mixtures of discrete [(L)CuII(NO2−)]+ plus ferrous heme-nitrosyl compounds; when the first NO(g) equiv reduces the heme center and itself is oxidized to nitrite, the second equiv of NO(g) traps the ferrous heme thus formed. For one µ-oxo heme-FeIII−O−CuII(L) compound, the reaction with NO(g) reveals an intermediate species (“intermediate”), formally a bis-NO adduct, [(NO)(porphyrinate)FeII-(NO2−)−CuII(L)]+ (λmax = 433 nm), confirmed by cryo-spray ionization mass spectrometry and EPR spectroscopy, along with the observation that cooling a 1:1 mixture of [(L)CuII(NO2−)]+ and heme-FeII(NO) to −125 °C leads to association and generation of the key 433 nm UV–vis feature. Kinetic-thermodynamic parameters obtained from low-temperature stopped-flow measurements are in excellent agreement with DFT calculations carried out which describe the sequential addition of NO(g) to the µ-oxo complex.

Synthetic Heme/Copper Assemblies: Toward an Understanding of Cytochrome c Oxidase Interactions with Dioxygen and Nitrogen Oxides

“…11 When employing the tridentate chelates, under the same experimental conditions, oxidation of NO (g) by μ-oxo [(F 8 )Fe III -O-Cu II (L)] + ensued considerably faster than for the parent analog, but still yielding the Cu(II)-nitrite plus ferrous heme-nitrosyl products.…”

“…Steric constraints imposed by o -fluorine substituents of the meso -phenyl groups on the attached porphyrin ring in F 8 ligand dictate structural properties of the cupric center resulting in deviation from the normal TBP geometry seen for [(tmpa)Cu II (X)] n+ (X = H 2 O, MeCN, Cl − , NO 2 − ) compounds. 11 …”

“…To expand on the initial study, we very recently reported a detailed mechanistic study 11 using different μ-oxo [(porphyrinate)Fe III -O-Cu II (L)] + complexes in which the heme or copper chelating ligand is modified (Scheme 4); ligand (L) for the cupric core was either a tripodal tetradentate pyridyl-alkylamine chelate or a related tridentate alkylamine ligand, and where two different tetraarylporphyrinates were employed for the heme core, one with electron-withdrawing peripheral substituents versus one with strong electron-donating groups.…”

“…11 A new μ-oxo complex, [(TMPP)Fe III -O-Cu II (tmpa)] + was synthesized and characterized and in its reaction with NO (g) at RT, there was an instantaneous change (as followed by UV-vis monitoring), giving a mixture of species, which eventually all converted to the expected final products, [(tmpa)Cu II (NO 2 )] + and (TMPP)Fe II (NO).…”

“…11 Later, this isosbestically converted to the final products in a first order process (Scheme 5, k dissoc. = 6.7 ×10 −3 s −1 at −20 °C, ΔH ‡ = 41.1 ± 0.1 kJ mol −1 and ΔS ‡ = −123 ± 2 J mol −1 K −1 ).…”