N-Arylhydroxamic Acids as Novel Oxidoreductase Substrates

Abstract

Keywords: Oxidoreductases / Redox chemistry / Electrochemistry / Ab initio calculations / StructureϪactivity relationships N-Arylhydroxamic acids (AHAs) are promising novel N−OH mediators for oxidoreductase catalysis. They are electrochemically active compounds with a redox potential of 0.31−0.41 V vs. SCE. Representative oxidoreductases, e.g. fungal peroxidase from Coprinus cinereus (rCiP), catalyze the oxidation of AHAs with apparent bimolecular constants (k ox ) of 7.1·10 3 to 1.5·10 7 m −1 s −1 at pH = 8.5 and 25°C. The limiting step in substrate oxidation was the reduction of compound II (Cpd II). The oxidation constants of N-hydroxyacetanilide (1a) and N-hydroxy-N-phenylbenzamide (2a), determined by a stopped-flow and steady-state method, were similar. The decrease in the reduction rate of Cpd II reduction rate decrease occurred at pK a = 8.5 for 1a and 7.7 for 2a. The nitroxyl radical of 1a, an intermediate in the oxidation, shows decreasing stability at alkaline pH. The structure−activity relationships (SARs) of these AHAs were analyzed within the

Intensification of Biocatalytical Processes by Synergistic Substrate Conversion. Fungal Peroxidase Catalyzed N-Hydroxy Derivative Oxidation in Presence of 10-Propyl Sulfonic Acid Phenoxazine

“…These compounds were used as mediators for laccase-catalyzed phenol [8] and polycyclic aromatic hydrocarbon degradation [9]. However, the oxidation of N-OH compounds by peroxidase and laccase is relatively slow [10,11]. Such reactivity was explained by low proton transfer rate in the active site of the peroxidase and laccase [12,13].…”

“…According to the results calculated, apparent bimolecular constants were (2.4± 0.2)·10 3 M −1 s −1 and (1.4±0.2)·10 4 M −1 s −1 for HPA and HPCM, respectively. The established values were in good agreement with those reported in [10,11].…”

“…It was shown that proton transfer accompanies the oxidation of ferulic acid by plant peroxidase [35]. Recently, it was shown that slow proton transfer rate could be the main factor that determines low N-aryl hydroxamic acids and N-aryl-N-hydroxy urethanes reactivity in rCiP-catalyzed process [10,11]. The calculations performed by Derat and Shaik also suggest that proton-coupled electron transfer is important for peroxidasecatalyzed substrate oxidation [36].…”

“…Initial rates of HPA and HPCM oxidation in the presence and absence of PPSA were monitored at 310 nm (ɛ 310 =8,900 M −1 cm −1 ) [10] and 307 nm (Δɛ 307 =4,900 M −1 cm −1 ) [11], respectively. The measurements were carried out at 25± 0.1°C in 20-mM Tris-HCl buffer solution (pH 8.5).…”

“…The value of k 22 for PPSA is assumed to be 2.2·10 9 M −1 s −1 [19] and redox potentials of HPA, HPCM, and PPSA are 0.611 V [10], 0.586 V [11], and 0.623 V [5] versus NHE, respectively. The data are presented as mean values±standard deviation.…”