Precise Recognition in Water by an Endo‐Functionalized Cavity: Tuning the Complementarity of Binding Sites

Abstract

Precise binding towards structurally similar substrates is a common feature of biomolecular recognition. However, achieving such selectivity—especially in distinguishing subtle differences in substrates—with synthetic hosts can be quite challenging. Herein, we report a novel design strategy involving the combination of different rigid skeletons to adjust the distance between recognition sites within the cavity, which allows for the highly selective recognition of hydrogen‐bonding complementary substrates, such as 4‐chromanone. X‐ray single‐crystal structures and density functional theory calculations confirmed that the distance of endo‐functionalized groups within the rigid cavity is crucial for achieving high binding selectivity through hydrogen bonding. The thermodynamic data and molecular dynamics simulations revealed a significant influence of the hydrophobic cavity on the binding affinity. The new receptor possesses both high selectivity and high affinity, which provide valuable insights for the design of customized receptors.

Precise Recognition in Water by an Endo‐Functionalized Cavity: Tuning the Complementarity of Binding Sites

“…These values are consistent with the previous calculation, and indicate a slight NÀ H distance change of 1 Å in the cavity. In addition, the crystal structures of 3 a in n-hexane/CH 2 Cl 2 , 3 b in acetone/ CH 2 Cl 2 , and 4 a in acetone/CH 2 Cl 2 were also obtained [22] (Figures S13-S15, Table S1), which further confirmed the authenticity of the hosts' structure. These crystal structures reveal that solvent molecules can reside in the cavities of these hosts by forming weak non-covalent interactions, such as hydrogen bonding.…”

“…Subsequently, the distances between two NÀ H bonds within the cavities of these hosts were measured, and show the order 1 a � 1b < 3c � 4c < 2 (Figure 2d, Figure S10). The single crystal structures [22] of 3 a and 4 a further confirmed that regulating the structure of the rigid skeleton can effectively adjust the distance between binding sites. As shown in Figure 3 (Figures S11-S12, Table S1), the NÀ H bonds in both 3 a and 4 a are oriented inward towards the well-defined cavities.…”

“…Therefore, when diamine is situated on the bisnaphthalene cleft side, it causes 4 c to be relatively flexible and easily aggregate in water. Furthermore, a suitable crystal structure [22] of 7@4 a has been obtained, which also exhibits hydrogen bonds and CH•••π interactions similar to those found in 7@3 a (Figure S49). This suggests that 4 c may also be capable of binding to these guests, despite its tendency to aggregate in water.…”

“…Despite several attempts to grow single crystals of host-guest complexes in water, such efforts have not been successful. Fortunately, by diffusing n-hexane into CH 2 Cl 2 , several suitable crystal structures of host-guest complexes have been obtained [22] (Figure 6, Table S2). These structures reveal that the guest molecules can be completely encapsulated within the cavity of 3 a, and two NÀ H•••O hydrogen bonds between 3 a and guests can be clearly observed.…”

Pillarurilarenes: Glycoluril-Expanded Pillararenes

“…Jiang and co-workers have performed pioneering work to develop macrocyclic naphthotubes with diverse inside-cavity binding sites through utilizing different functional groups as linkers of their naphthotubes. 3a, 5 Macrocyclic arenes, which are macrocycles composed of hydroxy-or alkoxy-substituted aromatic rings linked by methylene groups, have undergone rapid development in supramolecular chemistry in recent years. 6 Calixarenes and pillararenes are classic macrocyclic arenes that have been widely studied in various areas, including molecular recognition, self-assembly, supramolecular materials, etc., 7 due to their unique aromatic structure and facile derivatization.…”