Molecular Logic Gate for Sensing pH/Peroxynitrite\nwith Potential Applications in Cisplatin Treatment

Cisplatin\nis a common chemotherapy drug for multiple solid tumors;\nhowever, due to the nitrification of peroxynitrite (ONOO<sup>–</sup>), a series of side effects seriously affect its dose and efficacy.\nConsidering that the reactivity of ONOO<sup>–</sup> is significantly\naffected by pH in vitro, revealing their roles in living cells contributes\nto understanding the side-effect process induced by cisplatin. Herein,\nwe present a near-infrared fluorescent logic gate for sensing pH/ONOO<sup>–</sup>, which can accurately discriminate four scenarios\n(no analyte, analyte H<sup>+</sup> alone, analyte ONOO<sup>–</sup> alone, and H<sup>+</sup> + ONOO<sup>–</sup>) and which one\ncomes first. With this probe, the significant roles of pH and ONOO<sup>–</sup> in cisplatin treatment are disclosed, in which the\ncell account shows a dramatic reduction accompanied by decreased pH\nand upregulated ONOO<sup>–</sup> levels. By artificially recovering\nthe pH, the ONOO<sup>–</sup> content and cell account can maintain\na stable state, possibly due to the protection from acidification\nand nitration. This work provides an ideal pH/ONOO<sup>–</sup> logical sensor for revealing their potential roles under cisplatin,\nwhich is expected to proffer new insights into more related diseases\nand drug research.