Exploring the RNA‐Binding Potential of Three‐Dimensional Cyanines Derived From [2.2]Paracyclophane: A Structure–Property Relationship

This study reports the design, synthesis, and structure-property analysis of an original family of three-dimensional cyanine dyes based on the [2.2]paracyclophane (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.