Cucurbit[8]uril•guest complexes: blinded dataset for the SAMPL6 challenge

ABSTRACT

We investigated the formation of host guest complexes between cucurbit[8]uril (CB[8]) and 14 cationic guest compounds (2 – 15) by¹H NMR spectroscopy and isothermal titration calorimetry (ITC). Although these two component systems generally form 1:1 host:guest complexes, other stoichiometries are also observed (e.g. 1:2 host:guest and 3:1 host:guest) in situations where one guest fills roughly half of the cavity of CB[8] or where the guest contains multiple binding epitopes. We used the changes in chemical shift observed upon binding to glean information about the geometry of the host-guest complexes and in cases of slow exchange to confirm the host:guest stoichiometry. The complexes form with binding constants that range from 5.34 × 10⁴ to 8.26 × 10⁹ M⁻¹. The complexes are driven by negative Δ H° values (−2.00 to −14.4 kcal mol⁻¹). The data from these experiments were used as a blinded dataset for the SAMPL6 computational chemistry challenge.

Graphical Abstract

KEYWORDS:

• Cucurbit[n]uril (CB[n])
• SAMPL challenge
• host-guest chemistry
• binding constant
• drugs

Acknowledgments

We thank the National Science Foundation (CHE-1404911 and CHE-1807486 to L.I.) and the Department of Education (P200A150033 to L.I.; GAANN fellowship to S.M.)

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported by the Division of Chemistry [CHE-1404911 and CHE-1807486]; Department of Education [P200A150033].