Chromo-Fluorogenic Rhodamine-Based Amphiphilic Probe as a Selective and Sensitive Sensor for Intracellular Cu(I) in Living Cells

Fluorescent probes are widely studied for metal ion detection because of their multiple favorable properties such as high sensitivity and selectivity, quick response, naked eye detection, and in situ monitoring. However, optical probes that can effectively detect the Cu(I) level in cell interiors are rare due to the difficulty associated with selectively and sensitively detecting this metal ion in a cell environment. Therefore, we designed and synthesized three water-soluble probes (1–3) with a 1,3,5-triazine core decorated by three substituents: a hydrophobic alkyl chain, a hydrophilic maltose, and a rhodamine B hydrazine fluorophore. Among the probes, probe 1, which has an octyl chain and a branched maltose group, was the most effective at sensing Cu+ in aqueous solution. Upon addition of Cu+, this probe showed a dramatic color change from colorless to pink in daylight and displayed an intense yellow fluorescence emission under 365 nm light. The limit of detection and dissociation constant (Kd) of this probe were 20 nM and 1.1 × 10–12 M, respectively, which are the lowest values reported to date. The two metal ion-binding sites and the aggregation-induced emission enhancement effect, endowed by the branched maltose group and the octyl chain, respectively, are responsible for the high sensitivity and selectivity of this probe for Cu+ detection, as demonstrated by 1H NMR, dynamic light scattering, and transmission electron microscopy studies. Furthermore, the probe successfully differentiated the Cu(I) level of cancer cells from that of the normal cells. Thus, the probe holds potential for real-time monitoring of Cu(I) level in biological samples and bioimaging of cancer cells.