Structure, stability, and dynamics of the inclusion complexes formed by auranofin derivatives and hydroxypropyl-β-cyclodextrin

Abstract The inclusion compounds of auranofin (AF) and its iodide derivative (AF-I) with HP-b-CD were recently identified and characterized experimentally. In the present work, classical molecular dynamics and quantum computational GFN2-xTB method were applied to investigate the inclusion processes. As a result, both approaches addressed the AF-I@HP-β-CD as the most favorable system, as observed experimentally. The higher stability of AF-I@HP-β-CD was explained by entropy and solvation factors, with the GFN2-xTB method providing stability constant (logK1:1) in good agreement with experiment: 0.21 – 1.21 for AF@HP-β-CD and 1.31 – 2.33 for AF-I@HP-β-CD (experimental values are 1.48 and 2.52, respectively). The preferred inclusion mode for AF-I@HP-β-CD has the triethylphosphine (-PEt₃) group pointed toward the head portion of the HP-β-CD where the hydroxypropyl groups are attached (labeled as P2). The P2 mode showed short contacts between -CH₂CH₃ groups (-PEt₃) and -H3 only (inside the CD cavity), which is also supported by ROESY experiments.