Encapsulation of menthol by cyclodextrins-comparison between experiments and molecular simulations

Area of Science:

• Supramolecular Chemistry
• Computational Chemistry
• Food Science

Background:

• Cyclodextrins (CDs) are widely used for encapsulating flavor compounds.
• Selecting appropriate CDs for specific flavors through experiments is often time-consuming.
• Existing methods primarily rely on experimental encapsulation efficiency (EE) to assess CD-flavor interactions.

Purpose of the Study:

• To investigate and compare the binding effects of alpha-, beta-, and gamma-cyclodextrins (α-CD, β-CD, γ-CD) with menthol.
• To evaluate the suitability of molecular dynamics simulations as an efficient screening method for predicting CD-flavor complex formation.
• To establish reliable criteria for selecting suitable CDs for flavor encapsulation.

Main Methods:

• Experimental investigation of menthol encapsulation by α-CD, β-CD, and γ-CD.
• Molecular dynamics simulations to analyze complex stability, including conformation, RMSD, Rg, RDF, SASA, hydrogen bonds, and binding free energy (ΔGbind).
• Comparative analysis of experimental results with molecular simulation data.

Main Results:

• β-CD demonstrated the highest experimental encapsulation efficiency (EE) for menthol (36.54%), followed by γ-CD (33.35%), while α-CD showed no complex formation.
• Molecular simulations indicated the menthol/β-CD inclusion complex (IC) is the most stable (ΔGbind = -7.27 kcal/mol), and the menthol/α-CD IC is the least stable (ΔGbind = 2.59 kcal/mol).
• A high degree of consistency was observed between experimental findings and simulation results.

Conclusions:

• β-CD is the most effective cyclodextrin for menthol encapsulation among the tested variants.
• Molecular dynamics simulations provide a reliable and efficient alternative to experimental methods for predicting host-guest complexation in cyclodextrin systems.
• This approach can accelerate the selection of optimal cyclodextrin-flavor pairings.