Gallic acid is a naturally occurring low molecular weight triphenolic molecule identified as a potent antioxidant, protecting against various types of reactive species and non-radicals. Three novel carbon paste electrodes were developed for the potentiometric determination of gallic acid. Azamacrocyclic ionophors; cyclen, hexacyclen, and kryptofix-22 were utilized as recognition ionophores separately. A multi-walled carbon nanotubes/titanium oxide nanocomposite was employed as the ion-to-electron transducer in the designed sensors. The prepared transducer was characterized by FT-IR and TEM. Molecular docking was implemented to study the recognition mechanism between these ionophores and the gallic acid molecule. It revealed promising binding interactions between gallic acid and the three recognition ionophores, especially hexacyclen and Kryptofix-22. In studying the potentiometric response of the proposed sensors, they exhibited high stability, sensitivity, accuracy, and precision in the quantitation of gallic acid. Gallic acid can be accurately quantified over the linearity range of 1 × 10−1–1 × 10−3 M, 1 × 10−2–1 × 10−6 M, and 1 × 10−2–1 × 10−6 M with a Limit of detection (LOD) 4 × 10−4 M, 3 × 10−7 M, and 7 × 10−7 M, for CPE1, CPE 2 and CPE 3, respectively. The electrodes showed high efficiency in determining gallic acid in Krameria lappacea root alcoholic extract, black tea, green tea, and human plasma without sophisticated pretreatment steps.
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