Charting the structural and thermodynamic determinants in phenolic acid natural product – cyclodextrin encapsulations

Abstract

Cyclodextrins are pliable platforms that have served to optimize the pharmaceutic profile of numerous compounds and to enhance the stability of natural food additives. Caffeic and rosmarinic acid are natural products with proven health benefits, though their full therapeutic potential has not been exploited. To enhance their pharmaceutic profile, we developed cyclodextrin-based formulates and unveiled their thermodynamic and structural principles. The complexes’ stoichiometry was determined by ESI-MS. Solid-state and liquid NMR spectroscopy revealed the interactions and the topographical location of the caffeic and rosmarinic acid inside the cyclodextrin cavity. The theoretically analyzed HP-β-CD’s degree of substitution (DS) of caffeic and rosmarinic acids can explain the intensities obtained by 2D NOESY experiments. The thermodynamics and the affinity of the complexes were evaluated through isothermal titration calorimetry. In addition, the rosmarinic and caffeic acids as, also, their complexes showed considerable antimicrobial activity against common food spoilage and pathogenic bacteria. The generated data could provide the basis to understand the structural and thermodynamic determinants implicated in natural products – CD recognition and to develop platforms for the optimization of their pharmaceutical and stability profiles in order to be utilized as safe and stable natural antimicrobial food additives.

Communicated by Ramaswamy H. Sarma

Keywords:

• Caffeic acid
• rosmarinic acid
• 2-hydroxypropyl-β-cyclodextrin
• NMR spectroscopy
• isothermal titration calorimetry
• molecular dynamics
• antimicrobial activity

Disclosure statement

There are no conflicts to declare.

Additional information

Funding

This research has been financially supported by the General Secretariat for Research and Technology (GSRT) and the Hellenic Foundation for Research and Innovation (HFRI) (Scholarship Code: 1090). This work was supported by the CERIC funded programme (proposal number 20152002), programme for the promotion of the exchange and scientific cooperation between Greece and Germany IKYDA2015 and by the Cy-Tera Project (ΝΕΑ ΥΠΟΔΟΜΗ/ΣΤΡΑΤΗ/0308/31), which is co-funded by the European Regional Development Fund and the Republic of Cyprus through the Research Promotion Foundation.