Triphenylamine-Boronic-Acid-based Theragnostic Biomaterial for Diabetes with Concurrent Fluorescence Sensing of Glucose and Microviscosity

Abstract

Blood glucose and viscosity are two pivotal biomarkers associated with the chronic metabolic disorder, diabetes mellitus. Despite successful attempts on continuous monitoring of glucose, dual sensing of glucose and microviscosity with significant precision remains unexplored. To fill in this knowledge gap, a series of triphenylamine-boronic-acid-based fluorescence sensors were designed in this study. The triphenylamine-boronic acid derivatives (TPA-p-TBA, TPA-m-TBA, and TPA-o-TBA) were fabricated following the typical donor-π-acceptor arrangement, with triphenylamine as the electron-donating group and boronic acid as the electron-accepting group, enabling intramolecular charge transfer (ICT). In the presence of a cisvicinal-diol, viz., glucose, the boronic acid unit can undergo nucleophilic reaction and lose its electrophilicity, eventually quenching the ICT and restoring bright fluorescence. The glucose complex of the TPA-TBA derivative also experienced strong sterically restricted intramolecular bond rotation, facilitating transition to the local excited (LE) state from the non-radiative flexible twisted intramolecular charge transfer (TICT) state in highly viscous medium. This transition is validated by both improved aggregation-induced emission (AIE) and density functional theory (DFT)-based calculations. The TPA-TBA isomers showed selective interaction with glucose with a high binding affinity (3-9×10³ M^-1). The glucose-complex of the ortho derivative displayed the maximum fluorescence intensity enhancement owing to the high steric bulk close to the rotating bond. The detection limit for glucose using TPA-o-TBA was calculated to be the lowest (0.0211 mM) among the three derivatives. The TPA-TBA probes also showed better enzyme inhibition activity against alpha-amylase (IC₅₀ = 102.80±6.45 µg/mL) than the standard inhibitor acarbose.