Unraveling the Structure-Affinity Relationship between Cucurbit[n]urils (n = 7, 8) and Cationic Diamondoids.
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[7]·Diam(NMe3)2, the adamantane diammonium ion complexes (e.g., CB[7]·2,6-Ad(NH3)2and CB[7]·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 C═O portal. Comparative crystallographic investigation of CB[7]·Diam(NMe3)2, CB[7]·DiamNMe3, and CB[7]·1-AdNMe3revealed that the preferred geometry positions the+NMe3groups ≈0.32 Å above the C═O portal; the observed 0.80 Å spacing observed for CB[7]·Diam(NMe3)2reflects the simultaneous geometrical constraints of CH2···O═C close contacts at both portals. Remarkably, the CB[8]·IsoDiam(NHMe2)2complex displays femtomolar binding affinity, placing it firmly alongside the CB[7]·Diam(NMe3)2complex. Primary or quaternary ammonium ion looping strategies lead to larger increases in binding affinity for CB[8] than for CB[7], which we attribute to the larger size of the carbonyl portals of CB[8]; this suggests routes to develop CB[8] as the tightest binding host in the CB[n] family. We report that alkyl group fluorination (e.g., CB[7]·1-AdNH2Et versus CB[7]·1-AdNH2CH2CF3) does not result in the expected increase in Kavalue. 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.
Department of Chemistry and Biochemistry, University of Maryland , College Park, Maryland 20742, United States.
David
D
Sigwalt
Department of Organic Chemistry and Biochemistry, Ruđer Bošković Institute , Bijenička cesta 54, 10000 Zagreb, Croatia.
Marina
0000-0003-1629-3672
M
Šekutor
Department of Chemistry and Biochemistry, University of Maryland , College Park, Maryland 20742, United States.
Liping
L
Cao
Department of Chemistry and Biochemistry, University of Maryland , College Park, Maryland 20742, United States.
Peter Y
PY
Zavalij
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic , 16610 Praha 6, Czech Republic.
Jiří
J
Hostaš
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic , 16610 Praha 6, Czech Republic.|Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Palacký University , 77146 Olomouc, Czech Republic.
Haresh
H
Ajani
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic , 16610 Praha 6, Czech Republic.|Regional Center of Advanced Technologies and Materials, Department of Physical Chemistry, Palacký University , 77146 Olomouc, Czech Republic.
Pavel
P
Hobza
Department of Organic Chemistry and Biochemistry, Ruđer Bošković Institute , Bijenička cesta 54, 10000 Zagreb, Croatia.
Kata
K
Mlinarić-Majerski
Department of Chemistry, Ben-Gurion University of the Negev , Beer-Sheva 84105, Israel.
Robert
R
Glaser
Department of Chemistry and Biochemistry, University of Maryland , College Park, Maryland 20742, United States.
Lyle
0000-0002-4079-332X
L
Isaacs