The Solubility Studies and the Complexation Mechanism Investigations of Biologically Active Spiro[cyclopropane-1,3'-oxindoles] with β-Cyclodextrins.

In this work, we first improved the aqueous solubility of biologically active spiro[cyclopropane-1,3'-oxindoles] (SCOs) via their complexation with different β-cyclodextrins (β-CDs) and proposed a possible mechanism of the complex formation. β-CDs significantly increased the water solubility of SCOs (up to fourfold). Moreover, the nature of the substituents in the β-CDs influenced the solubility of the guest molecule (MβCD > SBEβCD > HPβCD). Complexation preferably occurred via the inclusion of aromatic moieties of SCOs into the hydrophobic cavity of β-CDs by the numerous van der Waals contacts and formed stable supramolecular systems. The phase solubility technique and optical microscopy were used to determine the dissociation constants of the complexes ( K c ~10 2 M -1 ) and reveal a significant decrease in the size of the formed crystals. FTIR-ATR microscopy, PXRD, and 1 H- 1 H ROESY NMR measurements, as well as molecular modeling studies, were carried out to elucidate the host-guest interaction mechanism of the complexation. Additionally, in vitro experiments were carried out and revealed enhancements in the antibacterial activity of SCOs due to their complexation with β-CDs.