Unraveling Biomimetic Hydrogen Bonds of Dinucleotides by a Crown‐Ether‐Functionalized Tetraphenylethene‐Based Cage

Natural biological systems achieve precise recognition and regulation of nucleic acids through multi-domain synergistic interactions. Herein, we report the design and synthesis of a crown-ether-functionalized tetraphenylethene-based cage (1•8X, X = PF₆- or Cl-) with two distinct recognition sites-four flexible, amphiphilic 18-crown-6 (18-C-6) units and a rigid, hydrophobic cavity. Its multi-cavity architecture offers an enzyme-like microenvironment, replicating the cooperative recognition behavior seen in natural receptors. As a result, 1•8Cl- promotes distinctive hydrogen-bonded assemblies of dinucleotides with various sequences in aqueous environments. Notably, 1•8Cl- facilitates a stable G•C•G•C quartet upon binding with two d(GpC), while assembling into an unprecedented C•C•C•C quartet in a 1:4 stoichiometric ratio with d(CpC). Additionally, 1•8Cl- selectively recognizes the 5'-base of dinucleotides or specifically binds to T base, promoting the formation of non-classical base-pairing patterns such as G•G, T•(H₂O)₂•T, and T•(K⁺)•T dimers in crystalline states. This study systematically investigates the hydrogen-bonding patterns of dinucleotides in biomimetic environments, providing new insights into the design of biomimetic receptors and understanding the diversity of non-classical nucleic acid structures.