Temperature-Driven Conformational Switching of Binaphthalene-Based Tetraimidazolium Macrocycles to Enhance Sequence-Selective Recognition of Dinucleotides in Water.

Developing artificial hosts with temperature-driven conformational switching behaviors facilitates our understanding of the temperature-dependent allostery and adaptation mechanisms in natural recognition systems. Herein, we report the design and synthesis of three pairs of water-soluble, enantiomeric binaphthalene-based tetraimidazolium macrocycles (SS/RR-1•4Cl- - SS/RR-3•4Cl-) as artificial hosts for exploring sequence-selective recognition of dinucleotides in aqueous media. Owing to the reversible rotational conformation of axially chiral binaphthyl units, SS-1•4Cl- demonstrates the conformational switching, converting from cis-conformation (SS-1_cis) to trans-conformation (SS-1_trans) by increasing temperature, thereby causing the recognition cavity to transition from a closed to an open state. Given its ability for temperature-driven conformational switching, SS-1•4Cl- exhibits temperature-cooperative enhanced binding behavior with d(TpA), with association constants (K_a) increasing to ∼10⁶ M^-1 at 323 K, up from ∼10⁴ M^-1 at 288 K. In contrast, its affinity for other dinucleotides, including d(ApT), d(GpC), and d(CpG), decreases to varying extents with increasing temperature. As a result, SS-1•4Cl-, with an ability of temperature-driven conformational switching, achieves an unexpected sequence-selective recognition for the sequence-complementary dinucleotide pair d(TpA) and d(ApT), with high sequence selectivity factors (K_rel = K_a[d(TpA)]/K_a[d(ApT)]) reaching up to ∼118.8 at 323 K, increased from ∼1.1 at 288 K, in water.