Oxidative Damage of S‐Containing Amino Acids by the Environmental Radical NO₃^.: A Kinetic, Product and Computational Study

Abstract

Dedicated to Prof. Ilhyong Ryu on the occasion of his 70 th birthday.Methionine, cysteine and cystine, which were acetylated at the N-terminus and methylated at the C-terminus, react rapidly with the environmental nitrate radical (NO 3 * ) with rate coefficients of 7.7 × 10 9 , 3.4 × 10 9 and 2.0 × 10 9 M À 1 s À 1 , respectively, in acetonitrile. Methionine (AcÀ MetÀ OMe) is successively oxidized via the sulfoxide (AcÀ MetOÀ Me) to the sulfone (AcÀ MetO 2 À OMe), with the latter step being also extremely fast with a rate coefficient of 1.2 × 10 9 M À 1 s À 1 . Computations predict formation of an initial charge transfer complex between NO 3 * and the S or SO moiety in Ac-Met-OMe, Ac-MetO-OMe and cystine (AcÀ Cys(SÀ S)Cys-OMe), respectively, which is followed by simultaneous SÀ O bond formation and NO 2 * expulsion. Calculations for the reaction of cysteine (Ac-Cys-OMe) with NO 3 * revealed side-chain oxidation to give a thiyl radical or a sulfenic acid as likely pathways. These findings highlight the potential harmful impact of NO 2 * /O 3 pollution on S-containing amino acid residues in peptides.

Damage of amino acids by aliphatic peroxyl radicals: a kinetic and computational study

“…Fig. 1 shows the amino acids studied in this work, which were protected at the N- and C-termini through acetylation and methylation, respectively, 17 to increase their solubility in MeCN/DTBP (7 : 3) (see below).…”

“…All compounds have been synthesised according to established procedures. 17 Experimental details are provided in the ESI †…”

Oxidative Damage of Aliphatic Amino Acid Residues by the Environmental Pollutant NO3·: Impact of Water on the Reactivity

“…The kinetic experiments were performed at 298 ± 1 K with an Edinburgh Instrument LP920 spectrometer using the 3rd harmonic of a Quantel Brilliant B Nd:YAG laser (6 ns pulse, 7–18 mJ, λ = 355 nm) to generate the reaction transient. − The detection system employed a Hamamatsu R2856 photomultiplier tube interfaced with a Tektronix TDS 3012C digital phosphor oscilloscope for transient absorption spectra. Kinetic measurements were carried out under pseudo-first order conditions with the substrate as the excess component.…”

“…The need for fundamental research to obtain an improved mechanistic understanding of the chemical interactions between air pollutants and biological systems has been highlighted recently. , In our ongoing effort to gain insight on how environmental NO 3 · could damage biomolecules present in the ASF, we have previously investigated the fundamental reactivity of amino acid residues and small peptides, purposefully excluding potential interfering interactions with the solvent, specifically hydrogen bonding. − Phenylalanine, , proline, cysteine, and methionine are rapidly attacked by NO 3 · through electron transfer (ET), with rate coefficients ranging from 1 × 10 7 to 8 × 10 9 M –1 s –1 (in acetonitrile (MeCN)), whereas the reaction with acylic aliphatic amino acid residues is slower (in the 10 6 M –1 s –1 range) and proceeds through HAT from Cα or activated positions in the side chain, as well as proton-coupled electron transfer (PCET) at the secondary amide moiety (the amino acids were always proteced by N-acylation and C-methylation) …”

“…• could damage biomolecules present in the ASF, we have previously investigated the fundamental reactivity of amino acid residues and small peptides, purposefully excluding potential interfering interactions with the solvent, specifically hydrogen bonding. 25−33 Phenylalanine, 29,30 proline, 32 cysteine, and methionine 33 are rapidly attacked by NO 3…”