How does sugammadex (a modified cyclodextrin) draw rocuronium into its lipophilic cavity? Sugammadex is a modified cyclodextrin: 8 member sugar ring with carboxyl thioether extensions. Rocuronium is an aminosteroid, 4 steroid rings and one protonated amine group. 

Sugammadex binds rocuronium really tightly. The reason for this is straightforward - lipophilic interactions with the inner cavity of the cyclodextrin, which is the perfect size because of the thioether extensions. The negatively charged carboxylate groups lock into place with the protonated amine. 

But the question asks how the rocuronium is initially drawn into the cavity, which makes less sense. I've only found one reference to this in the literature, in a figure caption that says the carboxylate groups interact with the four steroid rings. 

But how? The rings are not aromatic, so there is no anion-pi interaction. One would think the positively charged amine would interact with the carboxylate groups far more often, leading to the wrong orientation. If anything, the hydrophobic rings should be repulsed by the negative charge?





Figure 6: Encapsulation process: Sugammadex carboxyl groups interact with steroidal rings A, B, C, and D, drawing the aminosteroidal NMBA molecule into the cavity where additional non-covalent attractions hold the molecule securely in place.



Reference:NCBI
After consulting with a professor, the answer seems obvious.

The two negative charges repel each other when the free cyclodextrin molecule is in solution, resulting in an "open" conformation that has the carboxylate groups facing "out". The thioether chains interact with the rocuronium as it is drawn into the large open face of the molecule. As the positively charged nitrogen moves into place, the carboxylate groups "close", and lock the drug into place.