We report the measurement of the binding constants (Ka) for cucurbit[n]uril (n = 7, 8) toward four series of guests based on 2,6-disubstituted adamantanes, 4,9-disubstituted diamantanes, 1,6-disubstituted diamantanes, and 1-substituted adamantane ammonium ions by direct and competitive1H NMR spectroscopy. Compared to the affinity of CB·Diam(NMe3)2, the adamantane diammonium ion complexes (e.g., CB·2,6-Ad(NH3)2 and CB·2,6-Ad(NMe3)2) are less effective at realizing the potential 1000-fold enhancement in affinity due to ion-dipole interactions at the second ureidyl CO portal. Comparative crystallographic investigation of CB·Diam(NMe3)2, CB·DiamNMe3, and CB·1-AdNMe3 revealed that the preferred geometry positions the+NMe3 groups ≈0.32 Å above the CO portal; the observed 0.80 Å spacing observed for CB·Diam(NMe3)2 reflects the simultaneous geometrical constraints of CH2···OC close contacts at both portals. Remarkably, the CB·IsoDiam(NHMe2)2 complex displays femtomolar binding affinity, placing it firmly alongside the CB·Diam(NMe3)2 complex. Primary or quaternary ammonium ion looping strategies lead to larger increases in binding affinity for CB than for CB, which we attribute to the larger size of the carbonyl portals of CB; this suggests routes to develop CB as the tightest binding host in the CB[n] family. We report that alkyl group fluorination (e.g., CB·1-AdNH2Et versus CB·1-AdNH2CH2CF3) does not result in the expected increase in Ka value. Finally, we discuss the role of solvation in nonempirical quantum mechanical computational methodology, which is used to estimate the relative changes in Gibbs binding free energies.
ASJC Scopus subject areas
- Chemistry (all)
- Colloid and Surface Chemistry