Biomimetic Hydrogen‐Bonded Base Pairing of Nucleoside Triphosphates in Water by a Tetraphenylethene‐Based Octaimidazolium Cage

Abstract Studying biomimetic hydrogen‐bonded (H‐bonded) base pairing of nucleoside triphosphates (NTPs) in aqueous solutions using artificial recognition systems can enhance our understanding of the principles of base pairing in natural systems. Here, we report a water‐soluble tetraphenylethene‐based octaimidazolium cage ( 1 ) as an artificial host, which promotes the biomimetic H‐bonded base pairing of NTPs in water by forming their 1:1:1 hetero‐ternary or 1:2 homo‐ternary host‐guest complexes. Both the matched and mismatched H‐bonded base pairs of NTPs are stably captured within the cavity of 1 through the multiple noncovalent interactions of hydrogen bonds, CH⋯π/π⋯π interactions, electrostatic forces, and hydrophobic effect. ITC studies reveal the aqueous biomimetic recognition of 1 for these base pairs is dominantly driven by either classical (entropy‐driven, Δ S ≥ 0) or non‐classical (enthalpy‐driven, Δ H ≪ 0) hydrophobic effects. The X‐ray structure of the 1 •GTP 2 complex shows an unprecedented base pair (G:G*) with Watson‐Crick H‐bonded pattern, resulting from the prototropic tautomerism of normal guanine (G) to tautomeric guanine (G*). Through adaptive host‐guest chirality transfer, 1 can also act as a chiroptical sensor, exhibiting differentiated circular dichroism (CD) for these base pairs and enabling dynamic CD inversion to monitor the pH‐dependent transformation of GTP base pairs.