Volumetric Properties for the Binding of 1,4-Dioxane to Amide Naphthotubes in Water

Host-guest interactions between naphthalene-based molecular tubes and small molecules have been studied to understand selective recognition. However, the volumetric properties of complexation remain largely unknown. In this study, we investigated the volumetric properties for the binding of 1,4-dioxane to a pair of naphthotubes (i.e., anti- and syn-isomers), each possessing two inwardly directed amide groups in the hydrophobic cavity, using nuclear magnetic resonance and fluorescence spectroscopy coupled with pressure perturbation. We found that the partial molar volume change for the association of 1,4-dioxane with the naphthotube was -6.3 ± 0.1 mL/mol for the anti-isomer and 3.2 ± 0.4 mL/mol for the syn-isomer. Moreover, the hydrogen bonds of the naphthotubes with 1,4-dioxane were less compressible than those with water molecules, indicating that more rigid hydrogen bonds existed in the complexes with 1,4-dioxane. Molecular dynamics simulations showed that one opening of the cavity in the syn-isomer was widened because of the repulsion between the four COO^- charges, which allowed more water molecules to access the hydrophobic cavity than in the case of the anti-isomer. The difference in the partial molar volume change was explained by variations in the hydration of naphthotube hydrophobic cavities. The enhanced understanding of the molecular basis of volume changes during 1,4-dioxane-naphthotube complexation may provide insights into ligand binding to bioreceptors.