Development of a switching-type fluorescence sensor for the detection of boronic acid-containing agents

Since the therapeutic effect of boron neutron capture therapy is influenced by the intracellular distribution profile of boronoagents containing ¹⁰B atoms, it is necessary to establish a method that can determine the intracellular distribution profile of boronoagents. We aimed to develop a small molecule-based fluorescence sensor that changes its fluorescence properties upon complexation with the boronic acid moiety of a boronoagent. Thus, we designed a 2-(2-pyridyl)phenol derivative PPN-1 by introducing a N,O ligand substructure into a zinc sensor probe with excellent fluorescence properties. To investigate the effectiveness of PPN-1, we synthesized PPN-1 and evaluated its fluorescence properties compared to DAHMI, a current available boronic acid sensor. Consequently, PPN-1 showed favorable off/on fluorescence switching ability with a large Stokes shift after the addition of p-boronophenylalanine (BPA). Notably, after adding BPA, PPN-1 exhibited a rapid increase and reached a fluorescence plateau within 5 min, which is much shorter than the 2 h needed for DAHMI. Further, PPN-1 has excellent selectivity and detection and quantification limits similar to those of ICP-OES. These results demonstrated that PPN-1 is a practical scaffold for the detection and quantification of boronic acids and will provide essential insights for the development of boronic acid-targeted fluorescent sensors in the future.