Polarity-Specific and Pyrimidine-over-Purine Adaptive Triplex DNA Recognition by a Near-Infrared Fluorogenic Molecular Rotor

Triplex DNA structures have displayed a wide range of applications including nanosensing, molecule switching, and drug delivering. Therefore, it is of great importance to effectively recognize triplex DNA structures by a simple and highly selective manner. Herein, we found that a near-infrared fluorogenic probe of NIAD-4 with a molecular rotor (MR) merit can selectively recognize triplex DNA structures over G-quadruplex, i-motif, and duplex structures (Tri-over-QID selectivity), which is competent over the widely used MR probe of thioflavin T (ThT). Furthermore, NIAD-4 exhibits as well a high selectivity toward the ′pyrimidine-type′ triplex structures (Y:R-Y type) with respect to the ′purine-type′ triplex structures (R:R-Y type) (a Y-over-R selectivity). Interestingly, NIAD-4 recognizes the Y:R-Y triplex structures by a polarity-dependent manner. The 3′ end triplet is the preferential binding field of NIAD-4 with respect to the 5′ end one (a 3′-over-5′ selectivity) as the 3′ end triplet is more stable than the 5′ end one in the Hoogsteen hydrogen bond. It is expected that the adaptive stacking interaction between NIAD-4 and the 3′ end triplet favors the Tri-over-QID, Y-over-R, and 3′-over-5′ selectivities since this MR probe has three rotating shafts matching well with the triplet in topology. Such a high selectivity of NIAD-4 opens a new route in designing sensors with DNA structures switching between triplex, i-motif, and G-quadruplex structures.