Nitrogen Oxide Atom-Transfer Redox Chemistry; Mechanism of NO(g) to Nitrite Conversion Utilizing μ-oxo Heme-FeIII–O–CuII(L) Constructs

Shabnam Hematian †, Isabell Kenkel ‡, Tatyana E. Shubina ‡, Maximilian Dürr ‡, Jeffrey J. Liu †,Maxime A. Siegler †, Ivana Ivanovic-Burmazovic *‡, and Kenneth D. Karlin *†

† Department of Chemistry, Johns Hopkins University, Baltimore, Maryland 21211, United States

‡ Department of Chemistry and Pharmacy, University of Erlangen-Nuremberg, Erlangen 91058, Germany

J. Am. Chem. Soc., Article ASAP

DOI: 10.1021/jacs.5b02174

Publication Date (Web): May 14, 2015

Copyright © 2015 American Chemical Society

*ivana.ivanovic-burmazovic@fau.de, *karlin@jhu.edu

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.