Cucurbit[7]uril host-guest complexations of aza-, diaza-, and oxa, azaspirocycloalkanes in aqueous solution

ABSTRACT

The host-guest complexations of fifteen protonated azaspirocyclic, oxa,azaspirocyclic, and diazaspirocyclic guests, three-dimensional analogues of morpholinium, piperidinium, and piperazinium cations, respectively, with cucurbit[7]uril (CB[7]) were investigated using ¹H NMR spectroscopy in an acidic aqueous solution. The host-guest stability constants (K_CB[7]) for the protonated spirocyclic guests were determined to range from 10⁴–10¹¹ M⁻¹. The relative stability constants have been analyzed in terms of ring sizes and molecular volume (packing coefficient), and the presence and positions of additional oxygen and quaternary nitrogen heteroatoms. The larger the size of both the rings of the guest molecules the higher the observed binding constants for these guests with CB[7]. The largest values for K_CB[7] were found for 1- and 2-azaspiro[3.5]nonane, 2- and 8-azaspiro[4.5]decane, and 2-azaspiro[5.5]undecane, when the guest contained 9–11 heavy atoms. Adding oxygen heteroatoms decreased the binding constants by 2–3 orders of magnitude for the azaspirocyclic guests.

Graphical Abstract

KEYWORDS:

• Cucurbit[7]uril
• azaspirocycloalkanes
• host-guest complexes
• hydrophobic interactions

Acknowledgments

The Natural Sciences and Engineering Research Council of Canada is thanked for funding of this research in the form of a Discovery Grant (2015-06810).

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Natural Sciences and Engineering Research Council of Canada [2015-06810].