Electrochemical Oxidation of Amines Using a Nitroxyl Radical Catalyst and the Electroanalysis of Lidocaine

Abstract

The nitroxyl radical of 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) can electro-oxidize not only alcohols but also amines. However, TEMPO has low activity in a neutral aqueous solution due to the large steric hindrance around the nitroxyl radical, which is the active site. Therefore, nortropine N-oxyl (NNO) was synthesized to improve the catalytic ability of TEMPO and to investigate the electrolytic oxidation effect on amines from anodic current changes. Ethylamine, diethylamine, triethylamine, tetraethylamine, isopropylamine, and tert-butylamine were investigated. The results indicated that TEMPO produced no response current for any of the amines under physiological conditions; however, NNO did function as an electrolytic oxidation catalyst for diethylamine, triethylamine, and isopropylamine. The anodic current depended on amine concentration, which suggests that NNO can be used as an electrochemical sensor for amine compounds. In addition, electrochemical detection of lidocaine, a local anesthetic containing a tertiary amine structure, was demonstrated using NNO with a calibration curve of 0.1-10 mM.around the nitroxyl radical active site, and an adequate response current could not be obtained under physiological conditions. Iwabuchi and colleagues [22] reported that 2-azaadamantane N-oxyl (AZADO), which lacks steric hindrance around the active site, exhibited greater activity than TEMPO in organic synthesis reactions. Less-hindered nitroxyl radicals with various steric environments have been synthesized, and those with less bulky functionality exhibited greater activity [23][24][25][26]. Therefore, nortropine N-oxyl (NNO), which was modeled on AZADO, was synthesized in one step as a novel nitroxyl radical compound [27]. The NNO was capable of electrolytic oxidation of alcohols in neutral aqueous solutions. The NNO could be used in place of enzymes, allowing non-enzymatic analysis of glucose under physiological conditions [27]. Phenylboronic acid derivatives have been investigated as glucose sensors [28][29][30]. Phenylboronic acid (PBA) spontaneously binds with a moiety containing a diol [31]. The structural and electrical changes in PBA derivative probes when PBA bonds with the diol moiety can be used for glucose detection [32][33][34]. However, these probes had low specificity for glucose and did not respond under physiological conditions. Superiority of NNO was demonstrated from this report [27]. In contrast, TEMPO has catalytic oxidation ability toward amines as well as alcohols [35][36][37]. Therefore, the present study examined the electrolytic oxidation effect of NNO on amines under physiological conditions and compared the results with those obtained with TEMPO. The results demonstrated that NNO was a good electrochemical analysis probe for secondary and tertiary amines and for isopropylamine under physiological conditions (Figure 1). The oxoammonium ion, which is the active species, reacts with the amine to form hydroxylamine. The catalyst regenerates by reoxidation of hydroxylamine. Furthermore, ele...

Catalysis of electro-oxidation of antibiotics by nitroxyl radicals and the electrochemical sensing of vancomycin

“…Reports have indicated that NNO electrolytically oxidizes not only hydroxy groups but also secondary and tertiary amines. 27 Therefore, the cyclic voltammogram in the presence of meropenem also showed an increase in anodic current due to the progressive oxidation of amines. In addition, ethambutol showed a greater value for Δ I p than did the other two drugs due to the presence of a primary alcohol and secondary amine.…”

“…Using this catalyst, nonenzymatic detection of glucose and lactate under physiological conditions and electro-oxidation of amines were possible, which were difficult to achieve with TEMPO. 25,[27][28][29] First, the electrochemical responses to various antibiotics using NNO and TEMPO were compared. Low-molecular-weight compounds, such as ethambutol, acyclovir, and meropenem, were investigated (Fig.…”

Nitroxyl Radical/Copper-Catalyzed Electrooxidation of Alcohols and Amines at Low Potentials

“…NNO is synthesized in only one step from commercially available nortropine, whereas ABNO is synthesized in three steps from acetonedicarboxylic acid. 15,24)…”

“…Materials NNO and 9-azabicyclo[3.3.1] nonane N-oxyl (ABNO) were synthesized as reported previously. 15,24) Copper(I) trifluoromethanesulfonate toluene complex (CuOTf) was purchased from Sigma-Aldrich (St. Louis, MO, U.S.A.). TEMPO, tetrabutylammonium perchlorate (TBAP), 2,2′-bipyridyl (bpy), and 2,6-lutidine were purchased from Tokyo Chemical Industry Co., Ltd. (Tokyo, Japan).…”

“…We have studied enzyme-free electrochemical sensing of alcohols and amines based on nitroxyl radical catalysts acting as organocatalysts. [15][16][17][18] In this sensing mode, the nitroxyl radical is oxidized by an electrode into oxoammonium ion 1 (Fig. 1a), which oxidizes a substrate (an alcohol is shown as an example) to afford its corresponding oxidation product (a carbonyl compound is shown as an example) and hydroxylamine 2.…”