Insights into molecular recognition from the crystal structures of p-tert-butylcalix[6]arene complexed with different solvents

Abstract

Calixarenes are host molecules that can form complexes with one or more guest molecules, and molecular recognition in calixarenes can be affected by many factors. With a view to establishing molecular recognition rules, the host p-tert-butylcalix[6]arene (TBC6) was crystallized with different guest molecules (cyclohexane, anisole, heptane, toluene, benzene, methyl acetate, ethyl acetate, dichloromethane, tetrahydrofuran and pyridine) and the obtained structures were characterized by X-ray diffraction. With most solvents, 1:1 and/or 1:3 host–guest complexes were formed, although other stoichiometries were also observed with small guest molecules, and crystallization from ethyl acetate produced the unsolvated form. The calculated fill percentage of the TBC6 cavity was ∼55% for apolar guests and significantly lower for polar solvents, indicating that polar molecules can bind to apolar cavities with significantly lower packing coefficients. The most stable crystals were formed by 1:1 host–guest inclusion complexes. The ratio between the apolar surface area and the volume was used to predict the formation of inclusion versus exclusion complexes, with inclusion complexes observed at ratios <40. These findings allow the binding of potential guest molecules to be predicted and a suitable crystal packing for the designed properties to be obtained.

Conformations of p-tert-Butylcalix[8]arene in Solvated Crystal Structures

“…This high ratio suggests that the crystal structure exists in a metastable form, as TBC8 is well-known to also crystallize with pyridine in a 1:4 (CSD: XUNLEX, 6.4%) crystal structure or with acetonitrile in a 1:2 crystal structure (CSD: VARHAY, 3.3%) . Similar observation were also reported for the crystal structures of p-tert -butylcalix­[6]­arene with various solvents. , Of course, the packing motif and number of solvent molecules in the crystal structure play key roles in determining the void volume. In the case of the pleated-loop conformation, the number of solvent molecules determines the void volume.…”

“…62 Similar observation were also reported for the crystal structures of p-tertbutylcalix [6]arene with various solvents. 63,64 Of course, the packing motif and number of solvent molecules in the crystal structure play key roles in determining the void volume. In the case of the pleated-loop conformation, the number of solvent molecules determines the void volume.…”

Preferential Crystallization of tert-Butyl-calix[6]arene Chlorobenzene Solvate from a Solvent Mixture

“…m PhCl 2 molecules located outside the cavity form a channel along the [100] direction, thus separating the TBC6 bilayer (Figure c). This packing scheme is similar to that of the DCM solvate structure (1:4) …”

“…This packing scheme is similar to that of the DCM solvate structure (1:4). 17 The PhCl 2 derivative with the largest size (pPhCl 2 ) is solid at room temperature. Therefore, TBC6 with pPhCl 2 was dissolved in either toluene or ethyl acetate.…”

“…16 In the case of TBC6, it was determined that the ratio between the apolar surface area (APA) and volume (V) of the guest molecule predicts its location in the calixarene cavity and the stability of the formed crystal structures. 17 Guests with APA/ V < 40 form inclusion complexes. Most solvates with V < 100 Å 3,17 formed stable 1:1 crystal structures with the TBC6 host.…”