{"title":"Mefenamic Acid药物作为氧化还原活性羟基代谢物在炭黑表面的电化学氧化降解和捕获：介导的氧化和硫醇生物标志物的感知","authors":"Kondusamy Vignesh, Ayyakannu Arumugam Napoleon, Annamalai Senthil Kumar","doi":"10.1007/s12678-024-00907-5","DOIUrl":null,"url":null,"abstract":"<div><p>The elucidation of potential molecular structures and metabolites of pharmaceutical drugs remains a key area of research in medicinal chemistry, particularly due to drug-induced toxicity reactions. In this study, the electrochemical degradation of mefenamic acid (MFA) was conducted, leveraging biomimetic electron-transfer mechanisms. A carbon black (CB)–modified glassy carbon electrode (GCE) was employed as a biomimetic system to facilitate the in situ electrochemical conversion of MFA-drug into redox-active hydroxylated MFA metabolite (MFA-Redox). The chemically modified electrode (CME) demonstrated a surface-confined electronic feature of MFA-Redox, with a surface excess of 14.1 × 10<sup>−9</sup> mol cm<sup>−2</sup> under physiological conditions. Various physicochemical and chemical characterization techniques, including liquid chromatography-mass spectrometry (LC–MS/MS) analysis, confirmed the hydroxylated metabolite of MFA (<i>M</i><sub>w</sub> = 305.05 g/mol). Furthermore, the CME was used for the mediated oxidation of thiol groups, using cysteine (CySH)—a biomarker for cellular redox balance in physiologically neutral pH—as a model compound. This resulted in a well-defined, diffusion-controlled oxidation peak current. The Michaelis–Menten (MM) enzymatic kinetics model was applied to describe the oxidation process, yielding key kinetic parameters: the MM rate constant (<i>K</i><sub>M</sub>) of 0.060 mM, the first-order catalytic rate constant (<i>k</i><sub>c</sub>) of 0.4 s<sup>−1</sup>, and the heterogeneous electron-transfer rate constant (<i>k</i>'<sub>ME</sub>) of 9.7 × 10<sup>−2</sup> cm s<sup>−1</sup>. In a separate electroanalytical study, the performance of the CME for CySH detection was evaluated using amperometric i-t curves. The CME demonstrated a linear concentration range from 100 µM to 1 mM, with a sensitivity of 1.045 nA/µM and a detection limit of 3 µM. Importantly, the CME showed excellent selectivity, with no interference from uric acid, ascorbic acid, dopamine, glucose, and creatinine.</p><h3>Graphical Abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":535,"journal":{"name":"Electrocatalysis","volume":"16 2","pages":"224 - 236"},"PeriodicalIF":2.8000,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Electrochemical Oxidative Degradation and Trapping of the Mefenamic Acid Drug as a Redox-Active Hydroxy Metabolite on a Carbon Black Surface: Mediated Oxidation and Sensing of Thiol Biomarker\",\"authors\":\"Kondusamy Vignesh, Ayyakannu Arumugam Napoleon, Annamalai Senthil Kumar\",\"doi\":\"10.1007/s12678-024-00907-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>The elucidation of potential molecular structures and metabolites of pharmaceutical drugs remains a key area of research in medicinal chemistry, particularly due to drug-induced toxicity reactions. In this study, the electrochemical degradation of mefenamic acid (MFA) was conducted, leveraging biomimetic electron-transfer mechanisms. A carbon black (CB)–modified glassy carbon electrode (GCE) was employed as a biomimetic system to facilitate the in situ electrochemical conversion of MFA-drug into redox-active hydroxylated MFA metabolite (MFA-Redox). The chemically modified electrode (CME) demonstrated a surface-confined electronic feature of MFA-Redox, with a surface excess of 14.1 × 10<sup>−9</sup> mol cm<sup>−2</sup> under physiological conditions. Various physicochemical and chemical characterization techniques, including liquid chromatography-mass spectrometry (LC–MS/MS) analysis, confirmed the hydroxylated metabolite of MFA (<i>M</i><sub>w</sub> = 305.05 g/mol). Furthermore, the CME was used for the mediated oxidation of thiol groups, using cysteine (CySH)—a biomarker for cellular redox balance in physiologically neutral pH—as a model compound. This resulted in a well-defined, diffusion-controlled oxidation peak current. The Michaelis–Menten (MM) enzymatic kinetics model was applied to describe the oxidation process, yielding key kinetic parameters: the MM rate constant (<i>K</i><sub>M</sub>) of 0.060 mM, the first-order catalytic rate constant (<i>k</i><sub>c</sub>) of 0.4 s<sup>−1</sup>, and the heterogeneous electron-transfer rate constant (<i>k</i>'<sub>ME</sub>) of 9.7 × 10<sup>−2</sup> cm s<sup>−1</sup>. In a separate electroanalytical study, the performance of the CME for CySH detection was evaluated using amperometric i-t curves. The CME demonstrated a linear concentration range from 100 µM to 1 mM, with a sensitivity of 1.045 nA/µM and a detection limit of 3 µM. Importantly, the CME showed excellent selectivity, with no interference from uric acid, ascorbic acid, dopamine, glucose, and creatinine.</p><h3>Graphical Abstract</h3>\\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>\",\"PeriodicalId\":535,\"journal\":{\"name\":\"Electrocatalysis\",\"volume\":\"16 2\",\"pages\":\"224 - 236\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2024-11-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Electrocatalysis\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s12678-024-00907-5\",\"RegionNum\":4,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, PHYSICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Electrocatalysis","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1007/s12678-024-00907-5","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
Electrochemical Oxidative Degradation and Trapping of the Mefenamic Acid Drug as a Redox-Active Hydroxy Metabolite on a Carbon Black Surface: Mediated Oxidation and Sensing of Thiol Biomarker
The elucidation of potential molecular structures and metabolites of pharmaceutical drugs remains a key area of research in medicinal chemistry, particularly due to drug-induced toxicity reactions. In this study, the electrochemical degradation of mefenamic acid (MFA) was conducted, leveraging biomimetic electron-transfer mechanisms. A carbon black (CB)–modified glassy carbon electrode (GCE) was employed as a biomimetic system to facilitate the in situ electrochemical conversion of MFA-drug into redox-active hydroxylated MFA metabolite (MFA-Redox). The chemically modified electrode (CME) demonstrated a surface-confined electronic feature of MFA-Redox, with a surface excess of 14.1 × 10−9 mol cm−2 under physiological conditions. Various physicochemical and chemical characterization techniques, including liquid chromatography-mass spectrometry (LC–MS/MS) analysis, confirmed the hydroxylated metabolite of MFA (Mw = 305.05 g/mol). Furthermore, the CME was used for the mediated oxidation of thiol groups, using cysteine (CySH)—a biomarker for cellular redox balance in physiologically neutral pH—as a model compound. This resulted in a well-defined, diffusion-controlled oxidation peak current. The Michaelis–Menten (MM) enzymatic kinetics model was applied to describe the oxidation process, yielding key kinetic parameters: the MM rate constant (KM) of 0.060 mM, the first-order catalytic rate constant (kc) of 0.4 s−1, and the heterogeneous electron-transfer rate constant (k'ME) of 9.7 × 10−2 cm s−1. In a separate electroanalytical study, the performance of the CME for CySH detection was evaluated using amperometric i-t curves. The CME demonstrated a linear concentration range from 100 µM to 1 mM, with a sensitivity of 1.045 nA/µM and a detection limit of 3 µM. Importantly, the CME showed excellent selectivity, with no interference from uric acid, ascorbic acid, dopamine, glucose, and creatinine.
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