Heme/O2/*NO nitric oxide dioxygenase (NOD) reactivity: phenolic nitration via a putative heme-peroxynitrite intermediate.
An oxy-heme complex, the heme-superoxo species (tetrahydrofuran)(F(8))Fe(III)-(O(2)(*-)) (2) (F(8) = an ortho-difluoro substituted tetraarylporphyrinate), reacts with nitrogen monoxide (*NO; nitric oxide) to produce a nitrato-iron(III) compound (F(8))Fe(III)-(NO(3)(-)) (3) (X-ray). The chemistry mimics the action of *NO Dioxygenases (NODs), microbial and mammalian heme proteins which facilitate *NO detoxification/homeostasis. A peroxynitrite intermediate complex is implicated; if 2,4-di-tert-butylphenol is added prior to *NO reaction with 2, o-nitration occurs giving 2,4-di-tert-butyl-6-nitrophenol. The iron product is (F(8))Fe(III)-(OH) (4). The results suggest that heme/O(2)/*NO chemistry may lead to peroxynitrite leakage and/or exogenous substrate oxidative/nitrative reactivity.
Schopfer
Mark P
MP
Department of Chemistry, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
Mondal
Biplab
B
Lee
Dong-Heon
DH
Sarjeant
Amy A N
AA
Karlin
Kenneth D
KD
D000818:Animals; D032701:Biomimetics; D006418:Heme / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D009569:Nitric Oxide / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D010105:Oxygenases / Q000378:metabolism*; D030421:Peroxynitrous Acid / Q000378:metabolism*
D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D006418:Heme; D010105:Oxygenases; C114415:nitric oxide dioxygenase; D010100:Oxygen