Small-molecule fluorescent probes for non-destructive DNA detection: a systematic review of molecular skeletons, design strategies, and biological applications.

DNA detection and imaging are essential for elucidating genomic regulation, diagnosing diseases, and developing therapeutic agents. Small-molecule fluorescent probes serve as powerful non-destructive tools that enable the structural detection and visualization of DNA without compromising cellular or nucleic acid integrity. Based on their molecular skeletons, this review systematically summarizes advances in this field over the past decade. Seven categories of fluorophores are discussed: carbazole, benzothiazole/thiazole orange, pyridinium/quinolinium, triphenylamine, BODIPY, pyrene/tribenzoarene, and cyanine/coumarin derivatives. This review focuses primarily on their photophysical properties, fluorescence response mechanisms, non-covalent binding modes, and structural selectivity, as well as rational design strategies for the specific recognition of G-quadruplex, double-stranded DNA, i-motif, and three-way junction structures. Finally, future perspectives on the development of next-generation DNA-targeted probes for live-cell imaging and clinical translation are discussed.