Nuclear Magnetic Resonance Spectroscopic and Thermodynamic Characterization of Hydroxypropyl-cyclodextrin Inclusion...

Area of Science:

• Medicinal Chemistry
• Supramolecular Chemistry
• Pharmacognosy

Background:

• Herbal extracts contain bioactive molecules (BAMs) with potential therapeutic benefits but often possess unpleasant tastes.
• Cyclodextrins, particularly hydroxypropyl-cyclodextrins (HP-β-CD and HP-γ-CD), are widely used to encapsulate and modify the properties of guest molecules.
• Masking the taste of BAMs is crucial for improving patient compliance and the palatability of herbal formulations.

Purpose of the Study:

• To investigate the formation and stability of inclusion complexes between HP-β-CD and HP-γ-CD with key BAMs (thymol, carvacrol, eucalyptol) from herbal extracts.
• To determine the stoichiometry and binding interactions within these cyclodextrin-bioactive molecule complexes.
• To evaluate the influence of cyclodextrin cavity size and flexibility on complex stability and taste-masking potential.

Main Methods:

• Complexation of selected BAMs (thymol, carvacrol, eucalyptol) with HP-β-CD and HP-γ-CD.
• Characterization using 1H nuclear magnetic resonance (NMR) spectroscopy to analyze chemical shift changes.
• Determination of complex stoichiometry (1:1 HP-CD:BAM) and binding constants.
• Two-dimensional rotating-frame Overhauser effect spectroscopy (2D ROESY) to elucidate binding modes.
• Thermodynamic modeling to assess the contribution of hydrogen bonding.

Main Results:

• The stoichiometry of all investigated inclusion complexes was determined to be 1:1 (HP-CD:BAM).
• HP-γ-CD demonstrated enhanced binding constants and greater complex stability compared to HP-β-CD, attributed to its larger cavity and flexibility.
• NMR studies confirmed the inclusion of BAMs within the cyclodextrin cavities, with 2D ROESY providing insights into the binding orientation.
• Thermodynamic analysis indicated a significant contribution of hydrogen bonding to the complexation process.
• In a mixture of carvacrol and eucalyptol, carvacrol consistently formed the most stable complex with HP-CD.

Conclusions:

• HP-γ-CD is a more effective host cyclodextrin for forming stable inclusion complexes with the studied BAMs compared to HP-β-CD.
• The formation of 1:1 inclusion complexes is governed by factors including cyclodextrin cavity size, flexibility, and hydrogen bonding interactions.
• These findings support the use of HP-CDs, particularly HP-γ-CD, for taste-masking of bioactive molecules in herbal extracts, enhancing their therapeutic applicability.