Structural Studies of Piperine Inclusion Complexes in Native and Derivative β-Cyclodextrins

Area of Science:

• Pharmaceutical Sciences
• Supramolecular Chemistry
• Materials Science

Background:

• Piperine (PN), a key alkaloid in black pepper, exhibits valuable biological activities.
• Poor water solubility limits PN's bioavailability and therapeutic potential.
• Cyclodextrins (CDs) are widely used to enhance the solubility of poorly soluble compounds.

Purpose of the Study:

• To investigate the formation and characterization of piperine (PN) inclusion complexes with various cyclodextrin (CD) derivatives.
• To elucidate the structural and thermodynamic aspects of PN-CD complexation.
• To assess the stability and binding affinity of PN within CD cavities.

Main Methods:

• Phase solubility studies were conducted with native β-cyclodextrin (β-CD) and its derivatives (RM-β-CD, DM-β-CD, TM-β-CD, HP-β-CD).
• X-ray crystallography was employed to determine the solid-state structures of PN inclusion complexes.
• Molecular dynamics (MD) simulations and MM/GBSA calculations were used to evaluate complex stability and binding affinity in aqueous environments.

Main Results:

• Crystal structures revealed 1:2 guest:host stoichiometry for PN/β-CD, PN/DM-β-CD, and PN/TM-β-CD complexes.
• PN molecules were observed to thread through the hydrophobic cavities of CDs in specific orientations (tail-to-tail or head-to-tail).
• Phase solubility studies indicated B_s-type complexation for PN/β-CD and A_L-type for PN/RM-β-CD and PN/HP-β-CD, with 1:1 stoichiometry.

Conclusions:

• Piperine (PN) forms stable inclusion complexes with various cyclodextrins (CDs).
• The choice of CD derivative influences the stoichiometry and structural arrangement of the inclusion complexes.
• These findings highlight the potential of CD complexation to enhance the solubility and delivery of piperine.