Thermodynamic and Molecular Modeling Study of the Veratric Aldehyde/β-Cyclodextrin Inclusion Complex and Its...

The formation of the inclusion complex between veratric aldehyde (VER) and β-cyclodextrin (β-CD) was studied by combining molecular modeling with experimental techniques. Free energy profiles were generated using the Umbrella Sampling method in Molecular Dynamic simulations. Entropy and enthalpy profiles of the complex formation were also derived from these simulations, taking into account the possible orientations involved in the inclusion process. Hybrid QM/MM and density functional theory (DFT) methodologies were used to obtain a more accurate description of the structural features of the complexes. The thermodynamic parameters of the process were experimentally calculated from solubility diagrams registered at different temperatures. The inclusion complex was also synthesized in the solid state using two different techniques, freeze-drying and coevaporation, and its formation was confirmed by fourier transform infrared (FTIR) spectroscopy and powder X-ray diffractometry. The results of this study indicate that the formation of this complex is an enthalpy-driven process, improves the aqueous solubility of the aldehyde, and enhances its efficiency as an inhibitor of sweet potato polyphenol oxidase (PPO). In summary, the findings of this work suggest that the VER/β-CD inclusion complex may be a promising candidate for the formulation of food additives aimed at preventing or attenuating enzymatic browning.