This study reports the design, synthesis, and structure–property analysis of an original family of three‐dimensional cyanine dyes based on the 2.2paracyclophane (pCp) scaffold. By converting planar polymethine chromophores into three‐dimensional architectures, we developed fluorogenic dyes with enhanced selectivity for single‐stranded RNA containing stem‐loop motifs. Comparative studies with planar analogs show that benzothiazole‐ and benzoselenazole‐containing pCp derivatives exhibit strong fluorescence turn‐on upon nucleic‐acid binding, with responses varying by nucleic acid type and structure. Circular dichroism analyses suggest that these three‐dimensional dyes interact with RNA via a nonintercalative mode, distinct from classical planar intercalators. Expanding upon preliminary findings, this work explores an extended series of pCp‐derived cyanines, revealing how three‐dimensionality modulates both photophysical behavior and nucleic‐acid recognition. These results provide new directions for the design of selective RNA‐targeting ligands and for future exploration of their interactions with more complex RNA architectures.
Sun et al. (Thu,) studied this question.