Decoding the Interplayof Hydrogen Bonding, Dispersion,and Steric Interactions in Conformational Isomerism Among FunctionalizedPillar[<i>n</i>]arenes

Pillar[<i>n</i>]arenes have garnered popularity due to their unique pillar-shaped structure, which results in hydrophobic cavities. These cavities facilitate the formation of inclusion complexes with guest molecules through noncovalent interactions such as π–π stacking, hydrogen bonding, and van der Waals interactions. Such host–guest interactions enable diverse functionalities in pillar[<i>n</i>]arenes, including molecule recognition, self-assembly, and encapsulation. Nevertheless, it is important to note that the host–guest properties of pillar[<i>n</i>]arenes can be influenced by conformational changes, primarily driven by the rotation of hydroquinone units about their methylene bridge axis. These structural changes can lead to variations in underlying noncovalent and steric interactions, impacting the overall stability of the host–guest system and potentially leading to selective uptake of guest molecules. Additionally, due to relative energy differences, we expect a distribution of pillar[<i>n</i>]arene conformations at thermal equilibrium. In this work, we employ density functional theory to evaluate ground-state electronic structures of pillar[<i>n</i>]arene conformations across pillar[<i>n</i>]arenes of various sizes and functionalizations. We have aimed to explore the impact of dispersion interactions, hydrogen bonding, and steric interactions on the overall energetics of pillar[<i>n</i>]arene conformations and determine the dominant conformation at 298 K using a Boltzmann-weighted distribution. The relative strengths of hydrogen bonds across various pillar[<i>n</i>]arene conformations have been examined using Bader’s quantum theory of atoms in molecules topological analysis. Furthermore, we also assessed the solvation of pillar[<i>n</i>]arenes in water using an implicit solvent model that unveils quantitative distinctions in hydrogen bonding and relative dispersion contributions among various pillar[<i>n</i>]arene conformations. Finally, pillar[<i>n</i>]arene conformations with more complex functional groups such as primary amine, alkyl bromide, and carboxylic acid have been studied to evaluate the interplay between underlying interactions such as hydrogen bonding, dispersion, and steric interactions and their collective impact on the structure and energetics of pillar[<i>n</i>]arene conformations.