In silico investigation of complexes formed between chemical UV filters and cyclodextrins in water

UV filter - cyclodextrin complexes are investigated in silico in an aqueous environment using all-atom molecular dynamics simulations in the isothermal-isobaric statistical ensemble. The UV filters considered herein are octocrylene and avobenzone, which are used in commercial sunscreen products and together provide broad-spectrum skin protection (covering UV-A to UV-B radiation). The selected host molecules are β-cyclodextrin (β-CD) and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). In general, cyclodextrins have been assessed for protecting UV filters against photodegradation and oxidation, as well as for their ability to restrict UV filter permeation into deep skin layers. In all simulations, the starting point involves the UV filters and cyclodextrin molecules in the unbound state to determine whether noncovalent complexation is a spontaneous process. The main goal of this study is to examine in detail the complexes from a nanoscopic point of view, as well as the complexation process itself, paying particular attention to the thermodynamic description and the stability of the formed supramolecular complexes. In the framework of our analysis, several properties are calculated and, when possible, comparisons are made with published experimental data. Concerning thermodynamics, the binding free energy is estimated by applying a modified version of the Linear Interaction Energy (LIE) method. This method has been successfully applied in a number of studies involving complexes formed between cyclodextrins and small organic molecules. In the case of avobenzone, which contains a β-diketone group, both keto and enol forms are considered due to their tautomeric equilibrium and their distinct roles in photoprotection and photodegradation mechanisms.