TY - JOUR
T1 - Unraveling the Structure-Affinity Relationship between Cucurbit[n]urils (n = 7, 8) and Cationic Diamondoids
AU - Sigwalt, David
AU - Šekutor, Marina
AU - Cao, Liping
AU - Zavalij, Peter Y.
AU - Hostaš, Jiří
AU - Ajani, Haresh
AU - Hobza, Pavel
AU - Mlinarić-Majerski, Kata
AU - Glaser, Robert
AU - Isaacs, Lyle
N1 - Funding Information:
We thank the National Science Foundation (CHE-1404911 to L.I.), the Croatian Ministry of Science, Education, and Sports (grant 098-0982933-2911 to K.M.-M.), the Croatian Academy of Sciences and Arts (K.M.-M. and M.Š.), and the Ben-Gurion Univ. Scientific Relations Research Fund (R.G.) for financial support. This work was also supported by research project RVO 61388963 awarded to the Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, the Czech Science Foundation (grant number P208/12/G016) and by project L01305 of the Ministry of Education, Youth and Sports of the Czech Republic
Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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)2 and 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 CO portal. Comparative crystallographic investigation of CB[7]·Diam(NMe3)2, CB[7]·DiamNMe3, and CB[7]·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[7]·Diam(NMe3)2 reflects the simultaneous geometrical constraints of CH2···OC close contacts at both portals. Remarkably, the CB[8]·IsoDiam(NHMe2)2 complex displays femtomolar binding affinity, placing it firmly alongside the CB[7]·Diam(NMe3)2 complex. 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 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.
AB - 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)2 and 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 CO portal. Comparative crystallographic investigation of CB[7]·Diam(NMe3)2, CB[7]·DiamNMe3, and CB[7]·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[7]·Diam(NMe3)2 reflects the simultaneous geometrical constraints of CH2···OC close contacts at both portals. Remarkably, the CB[8]·IsoDiam(NHMe2)2 complex displays femtomolar binding affinity, placing it firmly alongside the CB[7]·Diam(NMe3)2 complex. 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 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.
UR - http://www.scopus.com/inward/record.url?scp=85014288032&partnerID=8YFLogxK
U2 - 10.1021/jacs.7b00056
DO - 10.1021/jacs.7b00056
M3 - Article
C2 - 28182422
AN - SCOPUS:85014288032
SN - 0002-7863
VL - 139
SP - 3249
EP - 3258
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 8
ER -