title: 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-Fe(III)-O-Cu(II)(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)Cu(II)(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-Fe(III)-O-Cu(II)(L) compound, the reaction with NO(g) reveals an intermediate species ("intermediate"), formally a bis-NO adduct, [(NO)(porphyrinate)Fe(II)-(NO2(-))-Cu(II)(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)Cu(II)(NO2(-))](+) and heme-Fe(II)(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.
authors.affiliation: †Department of Chemistry, Johns Hopkins University, Baltimore, Maryland 21211, United States.
authors.forename: Shabnam
authors.initials: S
authors.lastname: Hematian
authors.affiliation: ‡Department of Chemistry and Pharmacy, University of Erlangen-Nuremberg, Erlangen 91058, Germany.
authors.forename: Isabell
authors.initials: I
authors.lastname: Kenkel
authors.affiliation: ‡Department of Chemistry and Pharmacy, University of Erlangen-Nuremberg, Erlangen 91058, Germany.
authors.forename: Tatyana E
authors.initials: TE
authors.lastname: Shubina
authors.affiliation: ‡Department of Chemistry and Pharmacy, University of Erlangen-Nuremberg, Erlangen 91058, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Dürr
authors.affiliation: †Department of Chemistry, Johns Hopkins University, Baltimore, Maryland 21211, United States.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Liu
authors.affiliation: †Department of Chemistry, Johns Hopkins University, Baltimore, Maryland 21211, United States.
authors.forename: Maxime A
authors.initials: MA
authors.lastname: Siegler
authors.affiliation: ‡Department of Chemistry and Pharmacy, University of Erlangen-Nuremberg, Erlangen 91058, Germany.
authors.forename: Ivana
authors.initials: I
authors.lastname: Ivanovic-Burmazovic
authors.affiliation: †Department of Chemistry, Johns Hopkins University, Baltimore, Maryland 21211, United States.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Karlin
mesh_terms: D003300:Copper / Q000737:chemistry*; D005290:Ferric Compounds / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D009573:Nitrites / Q000138:chemical synthesis* / Q000737:chemistry; D009589:Nitrogen Oxides / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry*
chemical_list: D005290:Ferric Compounds; D009573:Nitrites; D009589:Nitrogen Oxides; D009942:Organometallic Compounds; D003300:Copper; D010100:Oxygen