Structure-Guided Aggregation-Regulated and Coordination-Assisted Zn–Porphyrins for Decoding Aminoglycoside Recognition in Real-Life Samples

Abstract

Herein, we report an aggregation-regulated Zn–porphyrin–based optical sensing platform for the selective detection of the aminoglycoside antibiotic neomycin in aqueous media and real-life samples. Three structurally related Zn–porphyrin derivatives with systematically varied peripheral substituents were designed to modulate supramolecular aggregation behavior and accessibility of the Zn²⁺ center. Comparative photophysical studies revealed that an optimal balance between aggregation and steric accessibility is essential for efficient sensing, with compound 1 exhibiting the most pronounced response. Neomycin binding triggered coordination-assisted and electrostatic reorganization of porphyrin aggregates, leading to a characteristic ratiometric fluorescence response involving quenching of the native porphyrinic emission and emergence of a distinct blue-shifted band at ~475 nm. The mechanistic investigations established aggregation modulation as the dominant transduction mechanism, driven largely by favorable entropic contributions. The sensing platform enabled quantitative neomycin detection with a low micromolar detection limit (0.75 µM) in complex matrices such as milk, along with accurate analysis of pharmaceutical formulations. Furthermore, translation of the system onto cellulose-based paper strips afforded a low-cost, portable, and instrument-free detection tool.