Re-engineering luminol: new frontiers in chemiluminescence chemistry

Abstract

Luminol and its derivatives have emerged as powerful chemiluminescent agents with broad applications in biomedical diagnostics, forensic science, and environmental monitoring. Despite their widespread use, luminol's limitations, including poor solubility, short luminescence duration, and sensitivity to environmental conditions, have driven extensive research into the synthesis of more efficient derivatives. This concise review presents recent advances in the molecular engineering of luminol derivatives, focusing on design strategies that employ electronic modulation (e.g., introduction of electron-donating or withdrawing substituents) and steric tuning (e.g., alkylation and ring substitutions) to optimize its chemiluminescence efficiency, kinetics, emission wavelength, solubility, stability, and applicability for specific environments (e.g., biological systems). The review also discusses how these structural modifications impact luminol's performance within integrated systems, including forensics, bioimaging platforms, immunoassay technologies and microfluidic sensors, thereby linking molecular-level design with macroscopic function. Emerging macromolecular and polymer-based luminol systems, such as those incorporating hydrophilic carriers, nanoparticles, enzyme-responsive linkers, surface-immobilized polymer brushes, and multi-functional hybrid platforms, are also highlighted for their potential to overcome solubility and biocompatibility barriers while enabling targeted delivery or signal amplification. Finally, key challenges and future perspectives are outlined, including the development of near-infrared-emitting derivatives, improved storage stability, and interdisciplinary strategies for translating luminol chemistry into next-generation diagnostics and environmental sensing platforms. By summarizing these advancements, this review underscores the evolving role of luminol chemistry in modern analytical science and its potential to revolutionize next-generation detection technologies.