Synergy-Promoted Specific Alkyltriphenylphosphonium Binding to CB[8]

Biological substrate specificity ensures that organisms
interact
accurately with biomolecular receptors, crucial for key functions
such as signaling and immunity. Nevertheless, this phenomenon is still
poorly understood, with host–guest chemistry offering a suitable
platform for studying simplified models. Herein, we report an in-depth
study of the host–guest chemistry of alkyltriphenylphosphonium
cations with cucurbit[8]­uril (CB[8]), initiated by the serendipitous
discovery of salt forming a tightly bound pseudoheteroternary 1:1
complex with CB[8]. A first generation of model substrates was designed
to explore an unusual binding mode characterized by the simultaneous
introduction of two distinct guest fragments within the host cavity.
Structural features of the complexes were elucidated using ESI-MS
and NMR 1D/2D techniques; thermodynamic properties were assessed by
isothermal titration calorimetry, and kinetic parameters were derived
from selective inversion–recovery NMR. Experimental results
aligned well with electronic structure calculations, revealing a reproducible
binding motif with submicromolar affinities. This peculiar complexation
mode involves a synergistic effect caused by steric crowding around
the P+ atom, facilitating the insertion of two aromatic
units into CB[8] while hindering association with CB[7]. Based on
these findings, a second generation of minimalistic substrates was
developed, preserving the synergistic interaction mode and exhibiting
specific binding to CB[8].