Antioxidant promotion of tyrosine nitration in the presence of copper(ii)

Abstract

Copper(II) is known to catalyze the generation of reactive nitrogen species in the presence of hydrogen peroxide, nitrite or nitric oxide, leading to tyrosine nitration, a biomarker for free radical species associated diseases. Here, we find that biological antioxidants such as ascorbic acid can promote tyrosine nitration in the presence of copper(II) and nitrite under aerobic and weak acidic conditions. Tyrosine nitration is demonstrated on both the β-amyloid peptide and angiotensin I. These studies show that (i) ascorbic acid works as a pro-oxidant in the presence of copper(II) to induce oxidation and nitration on peptides, (ii) both free and coordinated copper(II) can catalyze peptide oxidation and nitration, (iii) nitration occurs under mild acidic conditions (pH = 6.0-6.5).

Reactions of Co(III)–Nitrosyl Complexes with Superoxide and Their Mechanistic Insights

“…It should be noted that phenol nitration has been used extensively to provide evidence for the presence of metal-peroxynitrite species, 3a,3b,6a,14 and as mentioned, this reaction is of considerable biological importance. It is also noted that Co-NO complexes, 1 and 2 , do not react with the phenol.…”

“…Included is the capture of a peroxynitrite (or NO 2 ) intermediate via nitration of added phenols, which is analogous to biologically well established tyrosine nitration which effects biomolecule damage or participates in cellular signalling events. 3a,b,6,14 …”

“…Thus, a variety of outcomes can occur when metal complexes in varying oxidation states mediate reactions of NO (or NO + ) with differing reduced O 2 derivatives (e.g., superoxide or peroxide). Included is the capture of a peroxynitrite (or NO 2 ) intermediate via nitration of added phenols, which is analogous to biologically well-established tyrosine nitration, which effects biomolecule damage or participates in cellular signaling events. ,,, …”

“…While we do not have direct spectroscopic evidence for the postulated Co II –PN species, support for its formation comes from our finding that it can be intercepted by the addition of a phenolic substrate, here 2,4-di- tert -butylphenol to produce 2,4-di- tert -butyl-6-nitrophenol in good yields (>50%) with oxidative coupling occurring to most of the remaining phenol substrate (see the Experimental Section in the SI). Phenol nitration has been used extensively to provide evidence for the presence of metal–PN species, ,,, and as mentioned, this reaction is of considerable biological importance. It is also noted that Co–NO complexes 1 and 2 do not react with the phenol.…”