Molecular encapsulation of the aminosteroid phytotoxins solanidine and α-solanine by sugammadex: new insights into atomic-level interactions

Using cyclodextrins (CDs) as antidotes is of great interest in various fields of research due to their characteristic feature to strongly capture certain small apolar bioactive molecules. The application of a γ-CD derivative, sugammadex (SGM), as an antidote is exploited in the clinical practice to specifically reverse the effect of neuromuscular blocking agents. In the present work, we investigated the capability of SGM to capture naturally occurring aminosteroid phytotoxins, that have no known antidote to date. Using NMR spectroscopy, we identified exceptionally stable inclusion complexes between SGM and the phytotoxin solanidine (SN), and its glycoside α-solanine (ASN). The effects of pH and glycosylation on the complex stability were assessed in detail by NMR spectroscopy and isothermal titration calorimetry (ITC). Both SGM/SN and SGM/ASN complexes were found intact in the pH range of 2-12. Moreover, the stabilizing effect of the trisaccharide moiety of ASN was established. The association constants of 2.3 × 10⁶ M^-1 and 6.0 × 10⁶ M^-1 for 1:1 SGM/SN and SGM/ASN complexes, respectively, indicate the additional stabilizing effect of the trisaccharide substituent. Single crystal X-ray analysis of the SGM/SN system highlighted the importance of the numerous interactions between the host and the steroidal backbone of the guest that prevail in the crystalline state.