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

The inclusion compounds of auranofin (AF) and its iodide derivative (AF-I) with HP-β-CD were recently identified and characterized experimentally. In the present work, classical molecular dynamics and the quantum computational GFN2-xTB method were applied to investigate the inclusion processes. As a result, both approaches identified AF-I@HP-β-CD as the most favourable 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 a stability constant (logK_1:1) in good agreement with the experimental results: 0.21–1.21 for AF@HP-β-CD and 1.31–2.33 for AF-I@HP-β-CD (the experimental values are 1.48 and 2.52, respectively). The preferred inclusion mode for AF-I@HP-β-CD has a triethylphosphine (-PEt₃) group pointed towards the head portion of the HP-β-CD where the HP groups are attached (labelled P2). The P2 mode showed short contacts between -CH₂CH₃ groups (-PEt₃) and -H-3 only (inside the CD cavity), which is also supported by ROESY experiments.