Angewandte
Communications
Chemie
had not been achieved before, despite
[
23]
their attractive XB abilities.
We further intended to strengthen
the XB ability of the XB donor hemi-
sphere 1 by installing iodoethynyl(te-
trafluorophenyl) moieties to afford
hemisphere 4 (Figure 3A). (Iodoethy-
nyl)benzene derivatives exhibit supe-
rior XB donor abilities in solu-
[15d,22c,24]
[25]
tion
and in the solid state.
In fact, pentafluoro(iodoethynyl)ben-
zene···quinuclidine is among the stron-
gest neutral monodentate XB pair in
À1
solution (K = 117m , cyclohexane,
a
Figure 2. Single-crystal X-ray structure of XB capsule 1 ···2 . The supramolecular assembly
[22c]
C6
C6
2
98 K).
Initial calculations further
consists of twelve individual components: donor hemisphere 1 , acceptor hemisphere 2 , each
encapsulating one benzene molecule (green), and each cavitand is rigidified by four MeOH
C6
C6
suggested that the modifications out-
lined above might increase the binding
Gibbs energies of the altered capsule
molecules. ORTEP ellipsoids are set at 40% probability at 100 K. C gray, N blue, O red,
host
[19]
I purple, F yellow, Cguest green.
[
21]
dramatically.
Binding experiments
to determine K for capsule 1···3 by
F NMR binding titration revealed a—for XB interactions
a
1
9
The capsular geometry is in agreement with our initially
predicted model obtained by density functional theory (DFT)
unprecedented—slow exchange process relative to the
F NMR time scale (in deuterated benzene/acetone/metha-
[5c]
19
calculations. The two XB donor and acceptor hemispheres
undergo head-to-head assembly as earlier determined in our
nol 70:30:1, 283 K). When 3 was added to a solution of 1,
1
9
19
solution studies by F NMR titrations and 2D-HOESY NMR
a new set of F NMR signals for the capsular complex 1···3
[5c]
experiments.
The four halogen bonds have a length of
emerged (Figure 3B) and the association constant was
d(I···N) = 2.82 ꢀ and are shorter than the sum of the van-der-
determined to an unexpectedly modest value of K
=
a,1···3
4
À1
À1
Waals radii of the interacting atoms by about 20%. The CÀ (1.03 Æ 0.11) ꢁ 10 m
(DG = À5.3 Æ 0.1 kcalmol , see the
1
9
I···N angles are nearly linear (2 ꢁ 1718, 2 ꢁ 1788), as expected
for the strongly directional XB interactions. Each hemisphere
complexes one benzene guest deep inside the resorcin-
Supporting Information, Section S4). F Diffusion-ordered
[
26]
NMR spectroscopy (DOSY)
confirmed the presence of
1···3 by a significantly lower diffusion constant relative to
single cavitand 1 (see the Supporting Information, Table S12).
As we initially hoped to substantially strengthen the XB
association with 1···3 as compared to 1···2, we turned to
analyze the enthalpy–entropy compensation for the binding
process by vanꢂt Hoff analysis. The formation of capsule 1···3
is enthalpy-driven with an unexpectedly low binding enthalpy
[
4]arene scaffold and each hemisphere is stabilized by four
MeOH solvent molecules bridging the benzimidazole walls of
the cavitand by a circular hydrogen bonding array, as initially
[20]
shown by Rebek and co-workers.
The central unit of
capsule 1 ···2 is unable to bind guest molecules owing to the
C6
C6
intrusion of the aromatic units into the cavity (see the
Supporting Information, Figure S3). Independently, Sure and
Grimme calculated detailed structural features of this XB
capsule by applying optimized D3-dispersion methods to
DFT calculations (2% deviation in the d(N···I) distances, see
À1
of DH = À5.0 kcalmol and a nearly vanishing entropy (DS
À1 À1
ꢁ 0 kcalmol K ). This situation is in marked contrast to the
[
22c,27]
thermodynamic profiles of neutral XB interactions,
such
as in the complexation of 1···2 with a larger binding enthalpy
[21]
À1
the Supporting Information, Section S3).
of DH = À12.6 kcalmol and a compensating entropic pen-
À1
The capsular assembly is solely based on fourfold halogen
bonding and provides a platform to investigate XB in solution
with the aim of exploring the upper limit of XB association
constants and to uncover new aspects of that interaction in
solution. To investigate the influence of different XB donor
and acceptor motifs, we introduced two distinct structural
changes from the original XB capsule 1···2 with the intention
of enhancing association between the hemispheres. The
weakly Lewis basic lutidyl moieties of the XB acceptor
cavitand 2 were exchanged with quinuclidyl residues, one of
alty of TDS = À7.8 kcalmol (same solvent and same tem-
[
5c]
perature).
The X-ray analysis of 3 revealed the origin of the slow
1
9
complexation on the F NMR time scale and the modest
increase in capsular stability despite the much stronger XB
¯
acceptor moiety. The crystal structure (P1) shows a 10-
component assembly consisting of cavitand 3 solvated by
eight ordered MeOH molecules and an enclosed benzene
molecule. Four of the MeOH molecules participate in the
mentioned circular H-bonding array, stabilizing the confor-
mation of the benzimidazole cavity walls. The other four
solvate the strongly H-bond-accepting quinuclidine N-atoms
(d(O···N) = 2.7–2.8 ꢀ; Figure 3C). The energy barrier for the
desolvation of these N-atoms upon capsule formation is
substantial and leads to the observed slow exchange kinetics
on the NMR time scale.
[
22]
the strongest organic XB acceptor motifs known, to afford
tetraquinuclidyl cavitand 3 (Figure 3A; for synthetic details,
see the Supporting Information, Section S2). The vertical
fourfold alignment of the nitrogen atoms was confirmed by an
X-ray crystal structure of 3 (Figure 3C). Synthetic incorpo-
ration of quinuclidyl derivatives into XB acceptor scaffolds
2
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Angew. Chem. Int. Ed. 2016, 55, 1 – 7
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