Novel Conductometric Chemosensor Based on Methylenebis(Phosphonic Acid)-Modified Calixarene for L-Arginine Determination

Abstract

This study reports the synthesis of a novel methylenebisphosphonic acid calix[4]arene derivative and its application as a receptor layer in a conductometric chemosensor for the highly sensitive detection of L-arginine. The synthesized calixarene contains two methylenebisphosphonic acid fragments at the upper rim of the macrocycle, which serve as recognition sites for L-arginine, and two 3-(methylthio)propoxy groups at the lower rim, which enable immobilization on the gold electrode surface. The sensor based on synthesized calixarene demonstrated a pronounced response to L-arginine, which can be attributed to the cooperative interaction of the protonated amino and guanidinium groups of L-arginine with the methylenebisphosphonic acid groups of the calixarene receptor. Density functional theory (DFT) calculations were employed to elucidate the molecular interactions underlying the recognition of L-arginine by the calixarene receptor. The developed chemosensor demonstrated a low limit of detection for L-arginine (5.6 µM); a wide linear range (up to 1000 μM); a short response time (≤80 s); and a high response reproducibility (RSD = 1.3%). The stability constants determined by HPLC depended on the nature of the amino acid and ranged from logKA = 4.26 for leucine to logKA = 4.52 for L-arginine. Compared with previously reported L-arginine sensors, the developed conductometric chemosensor exhibits a competitive detection limit, a wider linear detection range, and significantly improved response reproducibility. The proposed calixarene-based chemosensor enables simple, highly sensitive, enzyme-free conductometric detection of L-arginine over a broad concentration range in aqueous solutions.