Increasing the Solubility of a Hydrophobic Molecule with Thymine-like Face by DNA via Supramolecular Interaction

Abstract

Poor water-solubility of hydrophobic drugs greatly hampers drug design and creats delivery problems. The traditional way to improve the solubility is to add hydrotropes or excipients to supress aggregations. Here, a novel mechanisim has been proposed based on supramolecular interactions and demonstrated with a small molecule, pyromellitic diimide(PD). This compound contains thymine-like ‘face’ and can interact with adenines through Watson-Crick and Hoogsteen hydrogen-bonding. Given the high water solubility of polyadenines[poly(A)], it is expected that poly(A) will greatly increase the PD solubility. Indeed, such an increased solubility was confirmed by ultraviolet-visible spectroscopy(UV-Vis) and polyacrylamide gel electrophoresis(PAGE) analysis. We believe that this strategy could be used to improve the solubility of other similar hydrophobic molecules.

Keywords

Polyadenine[poly(A)] / Pyromellitic diimide / Hydrogen bond force / Increased solubility

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