A spectroscopic and electrochemical investigation of the oxidation pathway of glycyl-D,L-methionine and its N-acetyl derivative induced by gold(III)

Abstract

The 1H nuclear magnetic resonance spectroscopy was applied to study the reaction of the dipeptide glycyl-D, L-methionine (H-Gly-D,L-Met-OH) and its N-acetylated derivative (Ac-Gly-D,L-Met-OH) with hydrogen tetrachloridoaurate(III) (H[AuCl 4]). The corresponding peptide and [AuCl 4] - were reacted in 1:1, 2:1, and 3:1 molar ratios, and all reactions were performed at pD 2.45 in 0.01 M DCl as solvent and at 25°C. It was found that the first step of these reactions is coordination of Au(III) to the thioether sulfur atom with formation of the gold(III)-peptide complex [AuCl 3(R-Gly-Met-OH-S)] (R=H or Ac). This intermediate gold(III) complex further reacts with an additional methionine residue to generate the R-Gly-Met-OH chlorosulfonium cation as the second intermediate product, which readily undergoes hydrolysis to give the corresponding sulfoxide. The oxidation of the methionine residue in the reaction between H-Gly-D,L-Met-OH and [AuCl 4]-was five times faster (k 2=0.363±0.074 M -1s -1) in comparison to the same process with N-acetylated derivative of this peptide (k 2=0.074±0.007 M -1s -1). The difference in the oxidation rates between these two peptides can be attributed to the free terminal amino group of H-Gly-D,L-Met-OH dipeptide. The mechanism of this redox process is discussed and, for its clarification, the reaction of the H-Gly-D,L-Met-OH dipeptide with [AuCl 4] - was additionally investigated by UV-Vis and cyclic voltammetry techniques. From these measurements, it was shown that the [AuCl 2] - complex under these experimental conditions has a strong tendency to disproportionate, forming [AuCl 4] - and metallic gold. This study contributes to a better understanding of the mechanism of the Au(III)-induced oxidation of methionine and methionine-containing peptides in relation to the severe toxicity of anti-arthritic and anticancer gold-based drugs. © The Author(s) 2011. This article is published with open access at Springerlink.com.