Benzene-, pyrrole-, and furan-containing diametrically strapped calix[4]pyrroles - An experimental and theoretical study of hydrogen-bonding effects in chloride anion recognition

Article abstract of DOI:10.1002/anie.200801426

(Figure Presented). Weak but important: The chloride anion binding properties of diametrically strapped calixpyrroles bearing benzene (see structure), pyrrole, and furan moieties in the strap have been studied in the solid state, in solution, and through theoretical analyses. The results obtained provide support for the notion that C-H...Cl^- hydrogen bonds are significant and contribute substantially to the Cl^- binding energetics.

Full text of DOI:10.1002/anie.200801426

Communications
DOI: 10.1002/anie.200801426
Not-So-Weak Hydrogen Bonds
Benzene-, Pyrrole-, and Furan-Containing Diametrically Strapped
Calix[4]pyrroles—An Experimental and Theoretical Study of
Hydrogen-Bonding Effects in Chloride Anion Recognition**
Dae-Wi Yoon, Dustin E. Gross, Vincent M. Lynch, Jonathan L. Sessler,* Benjamin P. Hay,* and
Chang-Hee Lee*
À1
Weak hydrogen bonds recently have arisen as a topic of
interest in supramolecular chemistry. Among the various
in the gas phase can be tuned from À8 to À16 kcalmol by
[1]
[11b]
altering the para substitution from NH to NO .
Although
2
2
interactions being studied, the CÀH···anion hydrogen bonds
there are some examples where complementary aryl CÀ
have drawn considerable attention. Positively charged groups,
H···anion interactions have been deliberately incorporated
[
7,12]
such as imidazolium cations, provide strong CÀH donors and
into the design of anion receptors,
to the best of our
have been used extensively in the design of numerous
knowledge, no efforts have been made to date to test
theoretical predictions through the synthesis and experimen-
tal study of a matched series of anion receptors. We now
report efforts along these lines.
[2]
anionophore architectures. There is increasing evidence,
however, that even charge-neutral CÀH donors may be strong
enough to be exploited effectively in anion recognition
chemistry. Such interactions, which involve both aliphatic
and aryl CÀH groups, have been inferred from gas-phase
In the context of ongoing efforts to develop the chemistry
of calixpyrroles (e.g., 1), we recently reported the synthesis of
[3]
[13]
studies, deduced from NMR spectroscopic studies through,
the strapped calixpyrrole 2. In this case, a single-crystal X-
[
4–7]
for example, chemical-shift changes,
state structures.
and observed in solid-
[
4,5,8]
A recent reviewof anion–arene adducts
notes that CÀH···anion hydrogen bonding, rather than
interaction with the p system, is by far the most prevalent
[9]
bonding motif observed in the solid state. These exper-
imental observations are supported by theoretical analy-
[
10,11]
ses.
For instance, Hay and Bryantsev have calculated that
[11a]
benzene CÀH···anion hydrogen bonds are significant,
being roughly half the strength of typical neutral NÀ
H···anion hydrogen bonds. In a subsequent theoretical
report, it was noted that the aryl CÀH···Cl binding energies
[
*] Dr. D.-W. Yoon, D. E. Gross, Dr. V. M. Lynch, Prof. J. L. Sessler
Department of Chemistryand Biochemistry
The Universityof Texas at Austin
Austin, TX 78712 (USA)
Fax: (+1)512-471-7550
E-mail: sessler@mail.utexas.edu
Dr. B. P. Hay
Chemical Sciences Division
Oak Ridge National Laboratory
Oak Ridge, TN 37830-6119 (USA)
ray diffraction study revealed the presence of a short CÀ
Prof. C.-H. Lee
À
[4]
H···Cl contact in the solid state. This evidence for hydrogen
bonding was later confirmed in solution by NMR spectro-
scopic means. However, because it provided only a single
datum point, it was not possible to assess the extent to which
Department of Chemistryand Vascular S ys tem Research Center
Kangwon National University
Chun-Chon 200-701 (Korea)
[
**] This work was supported bythe NIH (grant GM 58908 to J.L.S.), the
Korea Research Foundation Grant funded bythe Korean Govern-
ment (MOEHRD) (KRF-2006-214-C00047 to D.-W.Y.), and the Korea
Science and Engineering Foundation (grant no. R01-2006-000-
À
this CÀH···Cl interaction contributed to the overall chloride
anion binding process. In an effort to address this issue, we
have nowsynthesized the corresponding pyrrole- and furan-
strapped congeners 3 and 4, where 3 allows a comparison of
NH vs. CH hydrogen bonding and 4, which lacks a donor,
provides a “negative control”. The chloride anion binding
properties of this series were then analyzed in the solid state,
in acetonitrile and dimethylsulfoxide solution, and through
theoretical analyses. The results obtained provide support for
10001-0 to C.-H.L.), and B.P.H. acknowledges support from the
Division of Chemical Sciences, Geosciences, and Biosciences,
Office of Basic EnergySciences, US Department of Energy(DOE)
under contract number DE-AC05-00OR22725 with Oak Ridge
National Laboratory(managed byUT-Battelle, LLC).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200801426.
5
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Angewandte
Chemie
À
the notion that CÀH···Cl interactions are significant, at least
[
14]
within the well-defined
anion recognition environment
provided by this series of diametrically strapped calixpyrroles.
The key intermediate for the synthesis of the pyrrole-
strapped calix[4]pyrrole 3, pyrrole-2,5-dicarboxylic acid (5a),
[
15]
was prepared from the diester 6 (Scheme 1). The dicarbox-
ylic acid was then converted to the bis-acid chloride 7a by
heating at reflux in thionyl chloride, followed by simple
distillation and rigorous drying under high vacuum. Reaction
of 7a with 2.0 equiv of 5-(3-hydroxypropyl)-5-methyldipyrro-
[
13a]
methane 8
dipyrromethane 9a. Finally, acid-catalyzed condensation of
a in the presence of excess acetone afforded the desired
in the presence of pyridine yielded the bis-
9
Figure 1. Single-crystal X-ray diffraction structures of the anion-free
forms of receptors 3 (left) and 4·2MeOH (right).
[
16]
pyrrole-strapped calix[4]pyrrole 3 in 15% yield.
anion–receptor contacts in the
solid state, namely to the four
pyrrolic NH protons, to a proton
of the benzene strap, and to two
aliphatic protons (Figure 2, left).
In the present study, diffraction-
À
grade crystals of 3·Cl were
obtained by slowdiffusion of
methanol into a dichloromethane
solution of 3 containing an excess
of tetrabutylammonium chloride
(TBACl). The resulting X-ray dif-
fraction structure revealed that
the calix[4]pyrrole subunit exists
in the expected cone conforma-
tion and that the chloride anion
exhibits hydrogen bonding con-
tacts analogous to those observed
À
in 2·Cl . The average calixpyrrole
À
NÀH···Cl distances are compara-
ble in both complexes, being
Scheme 1. Synthesis of the pyrrole-strapped calix[4]pyrrole 3 and analogous furan system 4.
2
.407 Š and 2.425 Š for 3 and 2,
respectively. Similarly, the aver-
À
age aliphatic CÀH···Cl distances
The analogous furan-strapped calix[4]pyrrole 4 was syn-
thesized from furan-2,5-dicarboxylic acid (5b). This precursor
are comparable in both complexes: methylene 2.578 Š and
2.467 Š and methyl 2.945 Š and 2.979 Š for 3 and 2,
was readily prepared— through oxidation with KMnO —
4
from 2,5-diformyl furan 10, which in turn was obtained by
formylation of furan with nBuLi and DMF followed by acidic
work-up. In analogy to above, the resulting dicarboxylic acid
5
b was converted to the corresponding acid chloride 7b using
thionyl chloride; reaction with 8 gave the bis-dipyrromethane
b, which was condensed with acetone in the presence of
BF ·OEt to afford the desired furan-strapped calix[4]pyrrole
9
3
2
4
in 18% yield (Scheme 1). Both newcompounds, 3 and 4,
were characterized by standard spectroscopic means, as well
as by X-ray diffraction analysis (Figure 1). Interestingly,
compound 3 adopts a 1,3-alternate conformation in its
anion-free form, while compound 4 (containing two mole-
cules of methanol) adopts a 1,2-alternate conformation, at
least in the solid state.
Figure 2. Single-crystal X-ray diffraction structures of the chloride
anion complexes of the strapped calix[4]pyrroles 2 and 3. In both
[16]
Previously, we reported the X-ray crystal structure of
·Cl . Evaluation of this structure revealed three types of
À
À
cases, N H···anion and C H···anion contacts of ꢀ3 Š are shown. The
À
[4]
À
2
structure of 2·Cl was originallypublished in reference [4].
Angew. Chem. Int. Ed. 2008, 47, 5038 –5042
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5039

Communications
respectively. However, there is a large difference in the
To gain further insight into the contribution of the CÀ
H···Cl and NÀH···Cl contacts provided by the straps in 2 and 3,
the less expensive B3LYP/DZVP2 level of theory was used to
optimize the geometry of the chloride-bonded structures for
strapped calixpyrroles 2 and 3, as well as for the furan
analogue 4 (Figure 4). Starting from the crystallographic
distance involving the apical strap-derived contact, with the
À
pyrrole strap providing a closer NÀH···Cl contact by 0.63 Š
than the corresponding benzene CH interaction. The dihedral
angles around the 2,5-substituted pyrrole and the 1,5-sub-
stituted benzene moieties in the straps also differ, that is, the
benzene subunit is tilted more than the pyrrole subunit,
presumably to compensate the shorter net linker distance. At
present, no experimental structural information is available
for the corresponding chloride anion complex of the con-
generic furan-based system 4.
Electronic structure calculations were performed to assess
the relative strengths of the three types of hydrogen bonding
interactions in the absence of complicating effects arising
from steric constraints imposed by the ligand architecture and
environmental factors. As seen in Table 1, electronic binding
Table 1: Comparison of calculated electronic binding energies, DE
À1 [a]
À1
[
kcalmol ], with experimental gas-phase values for DH [kcalmol
]
À
for Cl complexes with simple hydrogen-bond donors.
Figure 4. Optimized B3LYP/DZVP2 geometries of the chloride anion
complex of the benzene-strapped calix[4]pyrrole 2 and the furan-
strapped calix[4]pyrrole 4. A corresponding view for the pyrrole-
strapped system 3, as well as Cartesian coordinates and absolute
energies for all three species, is included in the Supporting Informa-
tion.
[
b]
[c]
Donor
DE (DFT)
DE (MP2)
DH
[
3b]
pyrrole
benzene
methane
À23.09
À8.32
À3.06
À22.50
À8.42
À3.36
À18.8
[
3b,10a,17]
À8.6 to À10.5
[18]
À3.6
[
a] DE=E(complex)ÀE(chloride)ÀE(donor). Electronic structure calcu-
[19]
lations were performed with NWChem. [b] B3LYP/DZVP2. [c] MP2/
aug-cc-pVDZ.
coordinates, 2 and 3 were optimized under gas-phase con-
ditions. This yielded geometries that were little changed from
the solid state and had comparable average calixpyrrole NÀ
À
energies, DE, for complexes of Cl with the simple donors
À
pyrrole, benzene, and methane are fully consistent with
measured gas-phase DH values. The expected trend in
hydrogen-bond strengths is obtained with pyrrole > ben-
H···Cl distances (2.398 Š and 2.311 Š for 3 and 2, respec-
tively). Similarly, the average aliphatic CÀH···Cl distances are
comparable in both complexes (i.e., methylene 2.640 Š and
2.563 Š and methyl 2.933 Š and 3.019 Š for 3 and 2,
respectively). Optimization using starting coordinates derived
by replacing the benzene unit in 3 with a furan unit yielded a
[
11a]
zene > methane.
Moreover, these results confirm that the
À
CÀH···Cl contacts observed in the crystal structures of 2·Cl
À
and 3·Cl are attractive in nature and make a significant
À
contribution to the overall binding. In all cases geometries for
these 1:1 complexes (Figure 3) reveal closer contacts than
those observed in the strapped calixpyrrole macrocycles. This
effect is predominantly due to the fact that a single anion–
molecule interaction polarizes and redistributes the anion
charge differently than multiple anion–molecule interactions,
leading to stronger interactions and shorter distances.
putative geometry for 4·Cl . This complex shows the same
hydrogen-bonding motifs and distances as seen in 2 and 3,
with the exception that the furan moiety fails to provide an
additional hydrogen-bond donor. To obtain a measure of the
chloride affinity offered by each of the host configurations,
single-point energies were calculated after removal of the
À
chloride anion. Subtracting the energy of Cl and the host
binding configuration from that of the complex yields the
following DE values: À67.64 (3) < À63.46 (2) < À58.25 kcal
À1
mol (4). Consistent with the calculations on the simple
prototype donors, these binding energies predict that the
pyrrole-strapped system 3 should prove to be a better
receptor than the corresponding benzene species 2, and that
the latter system should prove to be a better receptor than the
[
20]
furan-strapped calix[4]pyrrole 4.
In light of the above prediction, attempts were made to
study the anion binding properties of the pyrrole-strapped
calix[4]pyrrole 3 using proton NMR spectroscopy. Unfortu-
nately, even in [D ]DMSO, which was expected to favor a
À
6
Figure 3. Optimized geometries for Cl complexes with pyrrole, ben-
rapid equilibrium, sets of peaks consistent with slow associ-
ation/dissociation kinetics (i.e., slowexchange) e wr e
observed. Nonetheless, these spectroscopic studies provided
insights into the mode of binding and the stoichiometry. For
zene, and methane. Distances are given below each structure at the
MP2/aug-cc-pVDZ and B3LYP/DZVP2 (in parentheses) levels of theory.
Cartesian coordinates and absolute energies for all optimizations are
included in the Supporting Information.
5
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Angewandte
Chemie
instance, in the absence of anions two singlets were observed
for the pyrrolic NHꢀs, namely one at d = 11.58 ppm (pyrrole
on the strap) and another at d = 9.43 ppm (calix[4]pyrrole).
However, upon addition of less than 1.0 equiv TBACl two
singlets appeared at d = 12.87 and 10.92 ppm. The b-pyrrolic
protons were also shifted upfield upon chloride anion binding
as expected (see the Supporting Information). Complete
appearance of these newsignals, wi th a corresponding
disappearance of the original signals, was observed after the
replacing the CH hydrogen-bond donor of the benzene-
strapped system by a pyrrolic NH donor increases the
chloride anion affinity by an additional order of magnitude.
Conversely, the furan equivalent 4, a “negative control”,
displayed a lower chloride anion affinity relative to the
benzene- and pyrrole-strapped receptors 2 and 3 by ca. one
and two orders of magnitude, respectively. As with the
[20]
theoretical analysis, other factors obscure/prevent/preclude
the quantitative assignment of the aryl CÀH···anion bond
À
addition of 1.0 equiv Cl . These observations are consistent
strength from these solution data. Nevertheless, it is impor-
tant to stress that the present experimental findings are fully
consistent with theory. They thus provide support for the
proposal that CÀH···anion interactions can be exploited to
with a strong 1:1 binding motif and the inclusion of chloride in
the cavity of the pyrrole-strapped calix[4]pyrrole 3. With the
furan-strapped calix[4]pyrrole 4, slowassociation/dissociation
kinetics were also observed in the case of TBACl. The NMR
signals of the pyrrolic NHꢀs were shifted downfield from d =
good effect in the design of anion receptors and that such not-
so-weak hydrogen bonds may have a role to play in terms of
explaining biological anion recognition processes.
9
.40 to 11.47 ppm. Additionally, the signals of the b protons
on the furan subunit were shifted upfield, along with the
calix[4]pyrrole b-pyrrolic protons, as in the case of 2 and 3.
Given that the system was undergoing slow exchange
relative to the NMR time scale, we chose the isothermal
titration calorimetry (ITC) as the method to quantify the
interaction of chloride (as the TBA salt) with calixpyrroles 1–
At present, we are working to generalize these findings by
extending the studies to other receptor systems and by
investigating the extent to which the choice of strapping entity
can affect the binding of other anionic guests. The results of
these efforts will be reported in due course.
4
(Table 2). Although we have already reported the chloride
Received: March 26, 2008
Published online: May 30, 2008
Table 2: Thermodynamic data for the interaction of calixpyrroles 1–4
with chloride.
Keywords: anions · calorimetry· h yd rogen bonds ·
molecular modeling · supramolecular chemistry
[
a]
.
À1
[b]
Host
TDS
DH
DG
Ka [m
]
Ka/K4
[
c]
5
6
7
5
1
2
3
4
À2.91
À1.90
À1.44
À1.67
À10.16
À10.54
À11.34
À8.87
À7.29
À8.64
À9.90
À7.20
2.2”10
2.2”10
1.8”10
1.9”10
1.2
12
95
1
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a
4
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[13a]
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6
6
À1
2
.2 ” 10 vs. 1.4 ” 10 m ; estimated errors < 10%). As
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Angew. Chem. Int. Ed. 2008, 47, 5038 –5042
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www.angewandte.org
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Communications
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chloride affinity offered by each binding configuration, we
recognize that it does not account for other contributions to the
overall binding affinity, such as conformational reorganization
that may occur prior to binding or the influence of solvation.
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