Biomimetic recognition of organic drug molecules in water by amide naphthotubes

Abstract

Molecular recognition in water is the basis of numerous biological functions. The key for efficient and selective recognition of an organic drug molecule is to bind both its polar and nonpolar groups. This is achieved by bioreceptors for which specific noncovalent interactions are efficiently used in a hydrophobic pocket. In contrast, most synthetic receptors cannot efficiently bind the neutral, polar groups of drug molecules and, thus, often exhibit poor binding selectivity and affinity. In this research, we report a systematic study on the binding behaviors of three types of macrocyclic hosts (amide naphthotubes, cucurbit[7]uril, and β-cyclodextrin) to 18 model compounds and 13 drug molecules. Our results show that the high desolvation penalty of polar groups of guests is the reason for the relatively low binding affinity of cucurbit[7]uril and β-cyclodextrin. However, amide naphthotubes with a biomimetic cavity bind efficiently and selectively to organic guests through hydrophobic effects and hydrogen bonding. Drug molecules with multiple polar groups can be better accommodated by these naphthotubes. The anti-configured naphthotube show good biocompatibility according to preliminary cell experiments and is capable of enhancing the water solubility of two poorly soluble drug molecules. Therefore, they may have practical applications in pharmaceutical sciences.