Fig. 5: Solvated Gibbs free energy profile for the dethreading process of ROT9 at ωB97X-D/def2-TZVP//def2-SV(P) level.

For each structure, the top illustration shows the side-on view of the complex, and the lower illustration shows the head-on view of the macrocycle itself with the axle hidden for clarity. The macrocycle is colored based on the distance of each atom to the best-fit plane of the 24-membered-ring in a rainbow color scale, with red signifies the atom is far away from the plane towards the tail end of the axle. Arrows depicts the direction of key geometric changes. The 4 plots on the bottom show the electron density (darker red-green-blue colormap with red/blue corresponding to 0–0.3 a.u.), and reduced density gradient map (brighter rainbow colormap with the blue to red color scale corresponding to 0.15–0.65 a.u.), which shows the nonbonding interactions, in the best-fit plane of the 24-membered-ring^66,67. SXRD: single crystal X-ray diffraction.