Effect of the pH on the thermodynamic stability of inclusion complexes of thymol and carvacrol in β-cyclodextrin in water

• Published in: Food hydrocolloids 2022-03, Vol.124, p.107307, Article 107307
• Main Authors: Cedillo-Flores, Oscar E., Rodríguez-Laguna, Norma, Hipólito-Nájera, Adrián Ricardo, Nivón-Ramírez, Didier, Gómez-Balderas, Rodolfo, Moya-Hernández, Rosario
• Format: Article
• Language: English
• Subjects: Carvacrol; Isothermal titration calorimetry; Molecular modeling; pKa; Solubility; Thymol; β-Cyclodextrin complexes
• ISSN: 0268-005X; 1873-7137
• DOI: 10.1016/j.foodhyd.2021.107307

Thymol and carvacrol are terpenes which have great potential to be used as preservatives in food and antimicrobial agents in medicinal herbs. As they present low water solubility and display acid-basic properties, inclusion in cyclodextrins and pH variations may enhance their properties. Here, the inclusion of thymol and carvacrol in β-cyclodextrin, at neutral and basic pH at 25 °C, is reported. The pKa for free thymol and carvacrol, and the pKa’ for the complexes HThy−βCD and HCar−βCD are determined by UV–Visible spectrophotometry. Inclusion in βCD has a stronger effect on ionization of thymol than on ionization of carvacrol. At neutral pH, the inclusion thermodynamic constants of the complexes HThy−βCD and HCar−βCD, reported as log βTer', are also determined by UV–Vis spectrophotometry. For the pHs 7.0, 8.0, 10.1 and 11.5, the log βTer' are obtained by isothermal titration calorimetry. Quantum chemistry molecular modeling is employed to reveal non-covalent interactions between terpenes and βCD molecules. Equations to calculate the inclusion constant βTer' at any pH value are derived. Furthermore, the Higuchi and Connors method is used to evaluate the increase of neutral terpenes solubility as result of the inclusion in βCD. Finally, using the experimental S0, pKa, pKa’ and βHTer, the terpenes solubility (S) are obtained in terms of pH and βCD total concentration. [Display omitted] •Stability of inclusion complexes into cyclodextrins is evaluated as a consequence of ionization of guest molecules.•While acidity constants of free thymol and carvacrol are slightly different, the acidity constants of their inclusion complexes with βCD are appreciably different.•Inclusion of thymol or carvacrol in βCD is enthalpic driven at low pH, and entropic driven at high pH.•Solubilities of terpenes are, for the first time, simultaneously described in terms of pH and cyclodextrin concentration.