Recent Progress in Small Molecule-Based Chemiluminescent Probes for Reactive Oxygen and Nitrogen Species

Chemiluminescence imaging, a highly sensitive and noninvasive modality, has emerged as an invaluable tool for bioimaging by virtue of its high signal-to-noise ratio and minimal background interference. The absence of an external excitation source enables chemiluminescent probes to directly convert chemical energy into light via oxidation reactions, yielding highly specific and quantifiable signals. Recent advances in small molecule-based chemiluminescent probes have opened further avenues for monitoring dynamic biological processes and pathological events in vivo, particularly those related to reactive oxygen and nitrogen species (RONS). These molecular probes are engineered to detect key RONS, such as singlet oxygen (¹O₂), hydrogen peroxide (H₂O₂), superoxide anions, peroxynitrite (ONOO^–), superoxide anions (O₂^•–), and hypochlorite (ClO^–), that play critical roles in oxidative stress, inflammation, cancer, and neurodegeneration. Their ability to offer real-time, quantitative insights into the presence and kinetics of RONS has significant implications for early disease diagnosis and targeted therapy. This review comprehensively summarizes the latest progress in the development of advanced chemiluminescent probes with simpler, more synthetically accessible, and modifiable structures that exhibit enhanced biocompatibility and broad application potential, while also discussing future challenges and opportunities in this rapidly evolving field.