A triphenylamine-based near-infrared fluorescence turn off probe for nitroreductase imaging

Abstract

Nitroreductase (NTR) is an essential biomarker for various diseases and widely used to evaluate the hypoxia status in tumor cells. In this work, we developed a near-infrared (NIR) fluorescence “on-off” probe PTP based on a triphenylamine scaffold, with an intrinsic long wavelength emission more than 700 nm. This probe showed typical aggregation-induced emission (AIE) properties with the increase of PBS fraction (fw), which might be attributed to the restriction of intramolecular motions (RIM) effect in high aqueous solution. The frontiers molecular orbitals (FMO) of the probe PTP and the resulting reduction compounds (PT-OH and TPA-OH) were calculated to determine their structure differences. The two nitro groups were reduced in response to NTR and then released the substance TPA-OH through the 1,6-rearrangement-elimination, resulting in simultaneous fluorescence decrease. This process was also demonstrated by the DFT/TD-DFT and docking calculations, indicating a favorable structural and spatial match between the probe and NTR. More importantly, the probe was successfully used to visualize the NTR distribution in living A431 cells with nontoxicity. It exhibited a time-dependent fluorescence quenching behavior at the cellular level, making it of great potential in NTR detection for other biosystems.