Decoding the Interplay of Hydrogen Bonding, Dispersion, and Steric Interactions in Conformational Isomerism Among Functionalized Pillar[n]arenes

Abstract

Pillar[n]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 non-covalent interactions such as π - π stacking, hydrogen bonding, and van der Waals interactions. Such host-guest interactions enable diverse functionalities in pillar[n]arenes, including molecule recognition, self-assembly, and encapsulation. Nevertheless, it is important to note that the host-guest properties of pillar[n]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 non-covalent 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[n]arene conformations at thermal equilibrium. In this work, we employ density functional theory (DFT) to evaluate ground state electronic structures of pillar[n]arene conformations across pillar[n]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[n]arene conformations and determine the dominant conformation at 298 K using a Boltzmann-weighted distribution. The relative strengths of hydrogen bonds across various pillar[n]arene conformations have been examined using Bader's QTAIM topological analysis. Furthermore, we have also assessed the solvation of pillar[n]arenes in water using an implicit solvent model that unveils quantitative distinctions in hydrogen bonding and relative dispersion contributions among various pillar[n]arene conformations. Finally, pillar[n]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[n]arene conformations.

Keywords: adsorbents; conformers; macrocyclic materials; pillar[n]arenes.

Figure 1.

Schematic representation of (a) non-rotated (A) and rotated (B) hydroquinone units where ‘R’ represents a variable functional group, unique conformations of (b) pillar[5]arenes and (c) pillar[6]arenes.

Figure 2:

Schematic representation of: (a) geometrical descriptors d_HA and θ_DHA used to characterize hydrogen bonds; (b) hydroquinone rotation about the methylene bridge axis in oppositely oriented hydroquinone units; and hydroquinone orientation in (c) P6C1 and (d) P6C7 conformations of per-methylated pillar[6]arene, resulting in a less accessible macrocyclic cavity in P6C7. Atoms are represented as follows: C = charcoal, H = white, O = red. Hydrogen bonds are shown with black dashed lines shaded in green. Planar surface passing through carbon atoms of the hydroquinone units in orientation ‘A’ is shown in blue, while the planar surface for orientation ‘B’ is depicted in red.

Figure 3.

Top views of per-hydroxylated pillar[5]arene conformations: (a) P5C1 and (b) P5C4; and per-methylated pillar[5]arene conformations: (c) P5C1 and (d) P5C4. Atoms are represented as follows: C = charcoal, H = white, O = red. Hydrogen bonds are shown with black dashed lines shaded in green.

Figure 4.

Computed relative energies with and without dispersion contributions for (a) per-hydroxylated and per-methylated pillar[5]arene conformations and, (b) per-hydroxylated and per-methylated pillar[6]arene conformations in vacuum (where E_Total is the relative energy of conformation with respect to ground state (most stable conformation), E_Disp is the relative dispersion contribution in a conformation with respect to ground state (most stable conformation); Lower energy values indicate higher stability)

Figure 5.

Top views of per-hydroxylated pillar[6]arene conformations: (a) P6C1 and (b) P6C7; and per-methylated pillar[6]arene conformations: (c) P6C1 and (d) P6C5 (Atoms represented: C = charcoal, H = white, O = red; Hydrogen bonds shown with black dashed lines shaded in green).

Figure 6.

Chemical structures of (a) P6C1 and (b) P6C7 per-methylamino pillar[6]arene; (c) P6C1 and (d) P6C7 per-ethylcarboxylated pillar[6]arene; (e) P6C1 and (f) P6C7 per-methylbromo pillar[6]arene. Atoms are represented as: C = charcoal, H = white, O = red, N = blue, Br = maroon. Hydrogen bonds shown with black dashed lines shaded in green.