4-Methoxyphenol: Applications in Electrochemical Detection and its Carcinogenicity

General Description

4-Methoxyphenol, a versatile organic compound, finds applications in various industries due to its role in organic synthesis. It is utilized as a polymerization inhibitor, UV inhibitor, dye intermediate, and in antioxidant synthesis for oils and cosmetics. In the field of electrochemical detection, 4-methoxyphenol acts as a redox reporter for real-time profiling of H2O2 in living cells, aiding in understanding cellular redox processes. However, caution is advised due to its potential toxicity and flammability. Additionally, studies have shown that 4-methoxyphenol exhibits forestomach carcinogenicity in rats, highlighting the importance of handling this compound with care.

Figure 1. 4-Methoxyphenol

Overview

4-Methoxyphenol is an organic compound with the molecular formula C7H8O2. It exists as a white or pale yellow crystalline solid with a distinctive odor. This compound is an important intermediate in organic synthesis, finding applications in the production of various drugs, fragrances, and coatings. Its primary uses include as a polymerization inhibitor for vinyl plastics, an ultraviolet inhibitor, a dye intermediate, and in the synthesis of antioxidant agents for edible oils and cosmetics. However, it should be handled with care due to its potential toxicity and flammability. ¹

Applications in Electrochemical Detection

4-Methoxyphenol serves a pivotal role as a latent redox reporter in the electrochemical detection of hydrogen peroxide (H2O2) within living cells. The utilization of 4-methoxyphenol as an electrochemical signal proxy enables real-time profiling of endogenous H2O2, which is crucial for understanding cellular redox homeostasis and pathological changes. In the study mentioned, a novel turn-on electrochemical redox probe, specifically 4-methoxyphenylboronic acid pinacol ester (4-MPBP), was developed for selective detection of H2O2 in live cells. This electrochemical probe consists of 4-methoxyphenol as the latent electrochemical reporter, coupled with a boronic acid pinacol ester recognition unit for H2O2 sensing. Upon analyte-triggered chemical transformation, free 4-Methoxyphenol is released, allowing for the electrochemical evaluation of H2O2 levels. The innovative approach integrates electrocatalytic signal amplification techniques, enhancing the sensitivity and dynamic detection range of the assay tool. By utilizing a modified electrode setup with polydopamine@carbon nanotube-molybdenum disulfide hybrids, the detection range of H2O2 is expanded, enabling trace-level sensing from 0.01 to 100 μM. This advanced methodology facilitates real-time monitoring of endogenously produced H2O2 in cellular models, demonstrating exceptional performance in in situ H2O2 release and tracking over time. The combination of 4-MPBP as a latent probe and electrocatalytic signal amplification strategy showcases promising capabilities for precise and sensitive detection of H2O2 in living cells, contributing significantly to the understanding of cellular redox processes and disease mechanisms. ²

Carcinogenicity

Carcinogenicity refers to the ability of a substance to cause cancer. In a study conducted on male and female F344 rats, the carcinogenic potential of 4-methoxyphenol and 4-methylcatechol (4-MC) was examined. Both 4-methoxyphenol and 4-MC are phenolic compounds that have structural similarities to known carcinogens. The known forestomach carcinogen, BHA, is structurally similar to 4-methoxyphenol, while catechol, a glandular stomach carcinogen, is structurally similar to 4-MC. During the study, groups of rats were given diets containing 2% 4-MP or 2% 4-MC for 104 weeks. Histopathological analysis revealed significant findings. In the case of 4-methoxyphenol, male rats showed atypical hyperplasias (67%), papillomas (50%), and squamous-cell carcinomas (77%) in the forestomach. Female rats exhibited atypical hyperplasias (37%), papillomas (23%), and squamous-cell carcinomas (20%) in the forestomach. On the other hand, 4-MC induced forestomach papillomas (70%) and squamous-cell carcinomas (53%) in both male and female rats. Additionally, it caused submucosal hyperplasias (90%), adenomas (100%), and adenocarcinomas (57%) in the glandular stomach with ulceration or erosion.  The study concluded that 4-methoxyphenol demonstrated unequivocal forestomach carcinogenicity, while 4-MC showed forestomach and glandular stomach carcinogenicity. Both substances exhibited enhanced cell proliferation and cytotoxicity, which are important factors for these non-genotoxic carcinogens. ³

Reference

1. Mequinol. National Center for Biotechnology Information. 2024; PubChem Compound Summary for CID 9015.

2. Manibalan K, Han S, Zheng Y, Li H, Lin JM. Latent Redox Reporter of 4-Methoxyphenol as Electrochemical Signal Proxy for Real-Time Profiling of Endogenous H2O2 in Living Cells. ACS Sens. 2019; 4(9): 2450-2457.

3. Asakawa E, Hirose M, Hagiwara A, Takahashi S, Ito N. Carcinogenicity of 4-methoxyphenol and 4-methylcatechol in F344 rats. Int J Cancer. 1994; 56(1): 146-152.

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