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 •4Clˉ – SS/RR ‐ 3 •4Clˉ) 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 •4Clˉ 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 •4Clˉ exhibits temperature‐cooperative enhanced binding behavior with d(TpA), with association constants ( K a ) increasing to ∼10 6 M −1 at 323 K, up from ∼10 4 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 •4Clˉ, 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.