A comparative study on inclusion complex formation between formononetin and β-cyclodextrin derivatives through...

Area of Science:

• Pharmacology
• Computational Chemistry
• Materials Science

Background:

• Formononetin, an isoflavone, has diverse therapeutic benefits but poor water solubility limits its industrial applications.
• Cyclodextrins (CDs) and their derivatives are effective in enhancing the solubility of poorly soluble compounds via inclusion complex formation.

Purpose of the Study:

• To investigate the interactions and thermodynamic parameters of formononetin inclusion complex formation with five common β-cyclodextrin (β-CD) derivatives.
• To identify the most effective β-CD derivative for enhancing formononetin's hydro-solubility.

Main Methods:

• Multiscale (1000 ns) explicit solvent molecular dynamics (MD) simulations.
• Umbrella sampling MD simulations to determine binding free energies and affinities.
• Analysis of non-bonded interactions, including hydrogen bonds and pi-interactions.

Main Results:

• MD simulations identified two primary binding conformations of formononetin within β-CD derivative cavities, with the benzopyrone ring frequently occupying the central cavity.
• Favorable binding free energies were observed for formononetin with most β-CD derivatives, excluding succinyl-β-CD (S-β-CD).
• The sulfobutylether-β-CD (SBE-β-CD)/formononetin complex exhibited the lowest binding energy, indicating the highest affinity and superior solubility enhancement potential.

Conclusions:

• SBE-β-CD is the most promising derivative for forming stable inclusion complexes with formononetin, significantly improving its hydro-solubility.
• The study provides a computational framework for evaluating β-CD derivatives' efficacy in solubilizing poorly soluble compounds.
• Findings support the potential of SBE-β-CD complexation for advancing formononetin's use in pharmaceutical and cosmetic applications.