7,7'-diamino-2,2'-diindolylmethane: A building block for highly efficient and selective anion receptors-studies in solution and in the solid state

Article abstract of DOI:10.1002/chem.201201909

The easy-to-make 7,7'-diamino-2,2'-diindolylmethane was used as a building block for the construction of anion receptors operating by hydrogen bonds. Its various bisamide and bisurea derivatives were designed and synthesised as acyclic as well as macrocyclic molecules, then their structural and anion binding properties were studied in solution and in the solid state. The bisamide receptors demonstrate high affinity towards oxoanions in highly polar and partially aqueous solutions (DMSO with up to 25 % H₂O) with significant selectivity for dihydrogen phosphate. Remarkably, the bisurea-based molecules are able to bind anionic guests even in pure methanol and show selectivity toward tetrahedral oxoanions, that is, hydrogen sulphate and dihydrogen phosphate. X-ray analysis revealed that both classes of molecules adopt a similar conformation in the solid state: a bent sheet shape with a binding pocket equipped with hydrogen-bond donors (four for the amides and six for the bisureas), whose orientation is particularly tailored for oxoanions. The results of ROESY NMR experiments are in agreement with the findings for the solid state and confirmed that both bisamides and bisureas can easily adapt the conformation with convergent hydrogen-bond donors, which is highly suitable for anion binding. Copyright

Full text of DOI:10.1002/chem.201201909

FULL PAPER
DOI: 10.1002/chem.201201909
7,7’-Diamino-2,2’-diindolylmethane: A Building Block for Highly Efficient
and Selective Anion Receptors—Studies in Solution and in the Solid State
Paweł Dydio,[a, b, c] Dawid Lichosyt,[a, b] Tomasz Zielin´ski,[a] and Janusz Jurczak*[a, b]
Dedicated to Professor Marek Chmielewski on the occasion of his 70th birthday
Abstract: The easy-to-make 7,7’-diami-
no-2,2’-diindolylmethane was used as a
building block for the construction of
anion receptors operating by hydrogen
bonds. Its various bisamide and bisurea
derivatives were designed and synthes-
ised as acyclic as well as macrocyclic
molecules, then their structural and
anion binding properties were studied
in solution and in the solid state. The
bisamide receptors demonstrate high
affinity towards oxoanions in highly
polar and partially aqueous solutions
(DMSO with up to 25% H2O) with sig-
nificant selectivity for dihydrogen
phosphate. Remarkably, the bisurea-
based molecules are able to bind
anionic guests even in pure methanol
and show selectivity toward tetrahedral
oxoanions, that is, hydrogen sulphate
and dihydrogen phosphate. X-ray anal-
ysis revealed that both classes of mole-
cules adopt a similar conformation in
the solid state: a bent sheet shape with
a binding pocket equipped with hydro-
gen-bond donors (four for the amides
and six for the bisureas), whose orien-
tation is particularly tailored for oxoan-
ions. The results of ROESY NMR ex-
periments are in agreement with the
findings for the solid state and con-
firmed that both bisamides and bis-
AHCTUNGTRENGNuUN reas can easily adapt the conforma-
tion with convergent hydrogen-bond
donors, which is highly suitable for
anion binding.
Keywords: amides · anion recogni-
tion · hydrogen bonds · indoles ·
structural analysis
Introduction
dustrial processes.[2] At the very heart of this area of chemis-
try[3] lies the design of both effective and selective anion re-
ceptors. Although the application of electrostatic attrac-
tion[4] or metal–anion complexation[5] can easily lead to
strong binding, these approaches nevertheless offer poor
control over the selectivity. Another approach utilises
weaker, but more directional interactions—such as those be-
tween Lewis acid and Lewis base,[6] p anions,[7] hydrophobic
effects[8] and hydrogen bonds[9]—in principle making it pos-
sible to adjust the geometry of the binding pocket to the
size and the topology of the desired anions, resulting in se-
lective binding. Hydrogen bonds have been one of the most
frequently used type[10] due to their relatively high strength
(which can be further multiplied by incorporating many
binding points) and due to the availability of functional
groups that can act as hydrogen-bond donors. Moreover,
such studies are inspired by natural systems, for example a
sulphate-binding protein,[11] which, by utilising only seven
hydrogen bonds, is capable of strongly and selectively bind-
ing the sulphate anion in water. Effective and selective
anion binding in protic solvents is highly desirable due to
practical applications,[12] but yet remains very challenging
despite continuous efforts.[13] The remarkable but scarce ex-
ceptions are mostly macrocyclic receptors equipped with
many anchoring points.[14]
Host–guest recognition is the cornerstone of supramolecular
chemistry,[1] and potential further applications make the un-
derstanding of the rules and principles that govern this phe-
nomenon highly desirable. Anionic species are of great im-
portance in many fundamental chemical and biological proc-
esses, therefore anion recognition has a highly applicable
potential in the fields of catalysis, analytics, medicine and in-
´
[a] P. Dydio, D. Lichosyt, Dr. T. Zielinski, Prof. J. Jurczak
Institute of Organic Chemistry
Polish Academy of Sciences
Kasprzaka 44/52, 01-224 Warsaw (Poland)
Fax : (+48)22-632-66-81
E-mail: jurczak@icho.edu.pl
[b] P. Dydio, D. Lichosyt, Prof. J. Jurczak
Department of Chemistry
Warsaw University, Warsaw (Poland)
[c] P. Dydio
Present address:
Van’t Hoff Institute for Molecular Sciences
University of Amsterdam, Amsterdam (The Netherlands)
Supporting information for this article (containing details concerning
the experimental procedures and spectral data for new compounds
(including images of H and 13C NMR spectra), titration experiments
1
1
and Job plots (including images of selected H NMR spectra), X-ray
In recent years, anion receptors containing amides, ureas,
pyrroles or benzopyrroles have attracted much interest,[15]
and some of them have shown remarkable affinity and high
selectivity for anionic guests even in demanding solvents,
structure elucidation (including CCDC numbers) and conformational
studies in solution (including images of ROESY NMR spectra)) is
available on the WWW under http://dx.doi.org/10.1002/
chem.201201909.
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
1
&
ÞÞ
These are not the final page numbers!

like DMSO/H2O mixtures.[16] One of the very successful
building blocks is 7-aminoindole, which has been used to
construct structurally simple amide- and urea-functionalised
anion receptors,[17] sensors[18] and transporters.[19] We antici-
pated that the connection of two of these units with the
methylene linker in the 2-positions of the indole rings would
lead to the new very attractive building block, 7,7’-diamino-
2,2’-diindolylmethane (DIM). Molecular modelling showed
that its simple amide derivatives 1 could bind oxoanions
with four convergent hydrogen bonds. Moreover, the pattern
of hydrogen-bond donors in the putative receptors 1 was
very similar to the one observed in 2,2’-bisamidodipyrrolyl-
methanes,[16a,b] which are very efficient, but chemically un-
stable anion receptors. Another approach would involve
synthesis of the urea-based compounds 2, which, as has
been shown before,[20] may result in a significant improve-
ment of the anion binding.
In our first approach, a key building block for our synthe-
sis—7,7’-bisnitro-2,2’-diindolylmethane (6)—was obtained in
a stepwise procedure, consisting of the Bartoli type synthesis
of 3-methyl-7-nitroindole (5), which was subsequently react-
ed with an aldehyde leading to the desired compound
(Scheme 2). We also developed a one-pot synthesis that
Therefore, we developed an easy method for the synthesis
of the 7,7’-diamino-2,2’-diindolylmethane building block 7
and used it to obtain both amid-based (1) and urea-based
(2) compounds, as well as their macrocyclic analogues 3 and
4 (see Scheme 1). Herein we report the details of the syn-
thesis together with the results of extensive studies of the
complexation properties and structural properties of these
receptors. Notably, the preliminary results of these studies[21]
have already found applications in the construction of very
selective transition-metal catalysts.[22]
Scheme 2. Synthesis of the receptors. a) CH3CH=CHMgBr; b) C2H5CHO,
HCl; c) H2, Pd/C; d) C2H5CHO, CH3CO2H; e) RCOCl, triethylamine
(TEA); f) RNCO with R=nBu and Ph for 2a and 2b, respectively, and
indole-7-amine, triphosgene, TEA for 2c;
g) ClOCACHTNURTGENNUG(CH2)7COCl, TEA; h) OCNAHCUTGNTREN(NUGN CH2)4NCO.
starts with the Schiff-base synthesis and follows with the
Fisher synthesis of indole 5 and its condensation with pro-
pional, in 44% overall yield. Importantly, the second path-
way does not require chromatographic purification of the
product, uses cheap and commercial-available building
blocks and can be performed on a multigram scale (>20 g)
within one working day, thus giving easy and inexpensive
access to the diindolomethane 6, and in consequence to its
further derivatives.
Next, the dinitro derivative 6 was smoothly and quantita-
tively hydrogenated, by using H2 and Pd/C, leading to bis-
AHCTUNGTREGaNNNU mine 7, which was a main building block for the synthesis
of the compounds 1–4. Amine 7 was reacted with three dif-
ferent acid chlorides leading to the amide-based compounds
1a–1c (in 79–92%); with two different isocyanates giving
the urea-based compounds 2a and 2b (79–92%), and finally
with triphosgene and 7-aminoindole providing compound 2c
(42%). The macrocyclic receptors 3 and 4 were obtained ap-
plying the high-dilution protocol in the reaction of the bis-
Scheme 1. Receptors 1–4 synthesised in this work.
Results and Discussion
ACHTUNGTRENaNUGN mine 7 with the appropriate acid dichloride and diisocya-
nate, respectively, providing both products in excellent
yields for macrocyclisations (67 and 64%, respectively).
Synthesis: The most straightforward synthesis of the diindo-
lylmethane derivatives consists of the synthesis of the indole
followed by its condensation with the carbonyl com-
pounds.[23] However, contrary to the reactivity of the pyrrole
rings, the 3-position of the indole ring is the most active one
for electrophilic substitution, thus direct condensation of the
unsubstituted indole leads to 3,3’-diindolylmethanes.[24]
Therefore, to facilitate the synthesis of the desired 2,2’-diin-
dolomethane derivatives we decided to block the 3-position
of the indole moiety with a methyl substituent.
Anion complexation studies: The association constants of
1
receptors 1–4 with various anions were determined by H
nuclear magnetic resonance titration technique. The addi-
tion of anions in the form of tetrabutylammonium (TBA)
salts to the solution of each compound usually triggered sig-
nificant the downfield shifts of the NH signals in the
1H NMR spectra, which indicated a fast (on the NMR time-
scale) equilibrium between free and anion-complexed recep-
&
2
&
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Highly Efficient and Selective Anion Receptors
FULL PAPER
Table 1. Binding constants for the formation of 1:1 complexes of com-
tors. Importantly, the highest shifts were observed for NH
signals, in contrast to other signals, thus confirming that
these groups take part in an anion binding event. The ab-
sence of the disappearance or significant broadening of the
NH signals ruled out deprotonation, which is a common
issue for anion receptors,[25] thus the main process taking
place in solution was anion complexation. The changes in
the chemical shift were used to calculate the values of the
binding constants by the nonlinear curve fitting to possible
binding models.[26] The stoichiometry of the complexes
formed was further confirmed by the Job plot analysis.[27]
Preliminary anion binding studies of the amide-based re-
ceptors 1a–1c showed their remarkable affinity towards di-
hydrogen phosphate and benzoate. Some of the values of
the association constants measured in the commonly used
solvent, DMSO/0.5% H2O, were above the limit of the
1H NMR titration technique (>104 mÀ1). Therefore, we next
used an even more competitive medium—DMSO with 5
and 10% water content—in which we were able to deter-
mine the binding constants in most cases. Typical titration
curves and Job plots for compounds 1a–1c are shown in
Figure 1.
pounds 1 with various anions in [D6]DMSO/H2O mixtures.[a]
Anion
Water [%][b]
Signal[c]
Ka [mÀ1
]
1a
1b
1c
30
ClÀ
0.5
0.5
0.5
0.5
5
amide
indole
amide
indole
amide
indole
amide
indole
amide
indole
amide
indole
amide
indole
amide
indole
amide
indole
amide
indole
amide
indole
amide
indole
–
470
20
30
30
[d]
80
<2
<2
1020
1660
–
BrÀ
<2
<2
2010
2140
3850
4460
7
20
À
PhCO2
>10000
>10000
>10000
>10000
–
À
[e]
[e]
H2PO4
ClÀ
–
[d]
20
20
<2
<2
260
300
130
400
–
–
–
–
–
150
10
10
7
BrÀ
5
<2
<2
360
340
980
990
–
À
À
PhCO2
5
1880
2060
>10000
>10000
540
À
H2PO4
PhCO2
5
[f]
[f]
[f]
[f]
[f]
[f]
[f]
[f]
[f]
[f]
[f]
[f]
10
10
25
590
–
–
–
À
H2PO4
H2PO4
H2PO4
5980
5640
210
210
8
À
<2
<2
<2
<2
–
–
–
À
[g]
–
The selectivity trends displayed by the amide receptors
1a–1c are similar and common for hydrogen-bonding recep-
8
[a] Values determined by 1H NMR titration experiments at T=298 K,
errors <10%, tetrabutylammonium salts were the source of the anions.
[b] [D6]DMSO/H2O mixture used as the solvent, water content (v/v) as
specified in the column. [c] NH NMR signal used for the calculations.
[d] Fitting failed due to a too small signal shift. [e] Fitting failed due to
signal broadening. [f] Not measured. [g] Determined in [D3]MeOH.
À [2]
tors: H2PO4À >PhCO2À >ClÀ >BrÀ >HSO4À >NO3 . In all
cases, the titration data had the best fit to a 1:1 receptor-to-
anion model, and this stoichiometry was also confirmed by
the Job plots. The binding constants determined independ-
ently by using the amide and indole NMR signals stay in
agreement with slightly higher values for the later ones.
The aliphatic amide 1a turned out to be the superior
anion receptor over the other analogues (Table 1), with an
exceptional affinity towards dihydrogen phosphate, which is
bound even in media as highly polar as DMSO with up to
25% water content as well as in pure methanol. The relative
À
selectivity of 1a towards H2PO4 over the second strongest
À
bound anion PhCO2 , is significantly high—approximately
by a factor of ten—and does not depend on the water con-
tent in the medium.
Unexpectedly, the phenyl derivative 1b binds anions
much weaker than 1a, despite the higher acidity of its NH
binding groups. A similar observation was reported for the
bisamidocarbazole anion receptors,[28] and it can be rational-
ised in terms of different steric hindrance of these side
groups, which can affect anion binding, as well as the prefer-
ences of the conformer, having an enormous effect on the
À
performance of the receptor.[29] For receptor 1b, H2PO4 is
still the strongest bound anion, but with the relative selectiv-
À
ity being only two over PhCO2 , which is the second stron-
gest bound anionic species.
Comparison of the titration results for receptors 1b and
1c reveals that introducing additional pyrrole moieties into
the latter does not significantly affect the affinity towards
the anions. Lower values for the binding constants and
smaller changes in the chemical shift triggered by anion
binding for the additional pyrrolyl NH signal in 1c (see the
Supporting Information) suggest that this group does not
significantly take part in the anion binding. Furthermore,
the structural analysis of 1c shows the unfavourable pre-or-
ganisation of the pyrrole moiety for anion binding (see
below).
Figure 1. 1H NMR titration curves and Job plots of compound 1a with
À
À
À
À
~
&
*
^
different anions
(
=H2PO4 ,
=PhCO2 ,
=Cl ,
=Br ) in
[D6]DMSO/5% H2O. Chemical shifts of the indole NH group (top) and
the amide proton (bottom).
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
3
&
ÞÞ
These are not the final page numbers!

J. Jurczak et al.
Table 2. Binding constants for the formation of 1:1 complexes of recep-
The observation that the presence of halogen anions trig-
gers relatively small chemical shifts of the amide NH signals,
compared to the shift of the indole NH signals (Figure 1 and
the Supporting Information), raised the question of whether
the amid groups take active part in the complexation of
these small anions or if their role is limited to increasing the
acidity of the indole NH bonding groups.[30] To answer this
question, we chose compound 6 as a model compound, be-
cause in this case the amide groups are substituted by even
stronger electron-withdrawing nitro groups,[31] which cannot
form hydrogen bonds but are of similar size, thus sterically
influencing the binding centre in a similar fashion. In
DMSO/0.5% H2O the putative receptor 6 was found not to
interact with the halide anions studied (ClÀ, BrÀ). We thus
decided to measure the affinity towards these anions in the
less demanding solvent acetone, which is structurally similar
to DMSO and still a more competitive medium than aceto-
nitrile or CH2Cl2. In this solvent, compound 6 interacts still
weakly with ClÀ, forming complexes with a relatively low as-
sociation constant (14mÀ1), while it does not bind to BrÀ at
all. Thus, these results confirmed a crucial role that is played
by the amide moieties in compounds 1 on their anion bind-
ing ability.[32]
tors 1a and 3 with various anions in [D6]DMSO/5% H2O.[a]
Anion
Signal[b]
Ka [mÀ1
]
3/1a
(Ka/Ka)
1a
3
ACHTUNGTRENNUNG
[c]
ClÀ
amide
indole
amide
indole
amide
indole
amide
indole
amide
indole
–
150
10
10
1880
2060
350
300
17
15
2690
2990
–
2
BrÀ
1.7
1.5
1.4
1.5
–
–
0.45
0.39
À
PhCO2
À
H2PO4
H2PO4
>10000
>10000
5980
>10000
>10000
2670
À[d]
5640
2190
[a] Values determined by 1H NMR titration experiments at T=298 K,
errors <15%, TBA salts were the source of the anions. [b] NH NMR
signal used for the calculations. [c] Fitting failed due to a too small signal
shift. [d] Determined in [D6]DMSO/10% H2O.
form 1:1 receptor-to-anion complexes with ClÀ, BrÀ and
À
HSO4 , as was shown by Job plot analysis (Figure 2). How-
ever, further aliquots of these anions can weakly interact
with the receptors, formally forming complexes of higher
stoichiometry, resulting in more complex equilibria. This is
indicated in the shape of the Job curves, as well as in the ti-
tration curves, by an additional small downfield shift of the
NH signals upon addition of further equivalents of anions
(Figure 2)—which also makes it impossible to determine the
Having established that the aliphatic bisamide 1a is the
most effective anion receptor, we were interested if its bind-
ing properties would be altered significantly when this build-
ing block is incorporated into a macrocyclic topology. To
answer this question we designed and obtained the model
macrocyclic bisamide 3 and compared its anion binding
properties with its acyclic analogue 1a. On the one hand, a
macrocyclic topology of 3 could be expected to lower its
conformational freedom and by pre-organising the cleft for
anion binding, improving the anion affinity.[29c,33] On the
other hand, the rigidified macrocyclic structure could also
hamper the anion-induced adjustment of the binding pocket
to the size and topology of the bound anion. The results of
1H NMR titration experiments show a relatively small and
varied effect of the macrocyclic topology on the anion affini-
ty depending on the used anion (Table 2). PhCO2 , ClÀ and
À
BrÀ are all bound slightly more strongly by the macrocyclic
amide 3, with association constants around 1.5 times higher
than for 1a, in contrast to the more topologically demanding
À
anion H2PO4 , which is bound more strongly by the acyclic
receptor 1a (the association constants being around 6000
and 2700mÀ1 in DMSO/10% H2O, for 1a and 3, respective-
ly), presumably due to the easier adjustment of the binding
pocket to this anion.
The previous studies on anion receptors derived from 7-
amino-2-indolecarboxylic acid revealed that the simple re-
placement of an amide moiety with a urea group can signifi-
cantly improve the affinity towards anions,[20] thus one might
expect superior anion complexation properties of the bis-
1
N
tration studies in DMSO/5% H2O showed that all urea re-
ceptors interact significantly with most of the anions studied
in this very polar medium (with the exception of NO3 ).
Figure 2. 1H NMR titration curves and Job plots of compound 2b with
À
~
&
*
different anions in [D6]DMSO/5% H2O ( =NHaindole
,
=NHburea
,
=
The results show that all three compounds preferentially
NHgurea).
&
4
&
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Highly Efficient and Selective Anion Receptors
FULL PAPER
values of the association constants. Judging by the shifts of
the NH signals, the urea NH groups play the largest part in
the binding of all three anions, whereas the indole NH
groups interact to a small extent with bromide anions, mod-
erately with chloride anions and significantly together with
all other NH groups in binding to the tetrahedral hydrogen
sulphate (Figure 2). Moreover, the titration studies with
those anions show that the additional NH indole groups in
2c do not take considerable part in anion complexation, be-
cause the signal of this proton is almost undisturbed by the
presence of anions.
groups is at first weakly affected by the anion binding,
whereas upon further anion addition the complex pre-organ-
ises and binds a second equivalent of the anion (Scheme 3).
Titration studies with dihydrogen phosphate anions re-
In contrast to the results found with halogen and sulphate
anions, the binding of benzoate by the bisureas 2 is more
complex. The titration curves and Job plots reveal the ten-
dency of the central diindolomethane core to bind one
equivalent of the carboxylic anion, whereas the pendant
urea groups tend to form complexes of higher stoichiometry
(Figure 3). For example, the signal of the outermost urea
NH group in 2a shifts to a small extent upon anion addition
up to one equivalent, whereas it starts moving downfield
considerably with further aliquots of anions. Compound 2c,
which can be considered a conjugation of two diindolylurea
subunits, one of which can saturate one carboxylate anion
by four hydrogen bonds,[16d,e,17d,18] tends to form a 2:1 anion-
to-receptor complex. However, it seems that the first equiv-
alent of benzoate is bound into the central core of the re-
ceptor, because the NH signal of the peripheral indole
Scheme 3. Proposed conformational changes in solution of 2c upon the
step-wise benzoate anion binding.
vealed strong interactions with all bisureas 2, as indicated by
the significant downfield shifts of the NH signals, up to Dd=
2.5 ppm (Figure 4). Compound 2a tends to form a 1:1 anion-
to-receptor complex, as shown by the Job plot as well as by
the titration curve of the urea signal, which reaches a pla-
teau upon addition of one equivalent of anion. However,
upon further anion addition the indole NH signal continues
to shift downfield, indicating the formation of complexes of
higher stoichiometry. Similarly, compound 2b binds strongly
À
to H2PO4 , but it expresses an even higher tendency to form
Figure 3. 1H NMR titration curves and Job plots of compounds 2 with
Figure 4. 1H NMR titration curves and JOB plots of compounds 2 with
~
&
&
*
*
benzoate anion in [D6]DMSO/5% H2O ( =NHaindole
,
=NHburea
,
=
dihydrophosphate anion in [D6]DMSO + 5% H2O ( =NHaindole
,
=
!
~
NHgurea
,
=NHdindole).
NHburea
,
=NHgurea, hexagon=NHindoleaverage, N=NHureaaverage).
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
5
&
ÞÞ
These are not the final page numbers!

J. Jurczak et al.
complexes with more equivalents of the anion. The results
for the third urea receptor 2c show that this compound
strongly interacts with two anions, forming a 2:1 anion-to-re-
ceptor complex. This last observation is in contrast with the
solid-state studies, which show formation of a 1:1 anion-to-
receptor complex (see below).
the studies in methanol solutions. Control titration experi-
ments in the presence of an excess of a base (triethylamine)
gave analogous results, diminishing the possibility of the
acid–base equilibrium between two complexes of the same
stoichiometry, rather than the equilibrium between two dif-
ferent complexes.
The complexity of the equilibria present in the aqueous
media in the case of H2PO4 may be also partially caused by
Although the titration studies in DMSO/5% H2O showed
a high affinity of compounds 2 towards most of the anions
studied, the values of the association constants could not be
determined due to the complex equilibria present in solu-
tion, including the formation of weak complexes of higher
stoichiometry. To quantify these interactions we decided to
apply the common remedy—to increase the polarity of the
solvent medium used, which enables the formation of
weaker complexes to be suppressed, allowing for the analy-
sis of the strongest and the most privileged complexes for-
med.[29c] To do so, we first decided to increase the water con-
tent in the medium, but came up against solubility issues, we
therefore changed the co-solvent to methanol. Initial experi-
ments in DMSO/25% MeOH mixtures revealed a high
anion affinity of compounds 2 and still the presence of com-
plex equilibria with higher stoichiometry complexes even in
this very demanding medium. Therefore, we next used pure
methanol, considered as one of the most demanding sol-
vents for anion binding,[13a] especially for hydrogen-bond op-
erating anion receptors. In this medium, solvent molecules
not only strongly bind to hydrogen-bond-donating groups of
receptors, but also strongly solvate anionic species. Thus, the
solvent molecules have to be replaced from the host and the
guest prior to complex formation, hence hampering or even
completely suppressing the anion binding event.
The interaction of the bisureas 2 with anions in methanol
manifests itself in the considerable downfield shift of both
the urea and the indolyl NH signals (Figure 6). The record-
ed titration curves allowed us to determine the stability con-
stants for most of the studied
À
the weakly acidic character of this anion, because the proto-
nation equilibria could occur along with the binding event.
One plausible scenario for example is a proton transfer
from the bound anion to the free anion in solution, and this
process has been reported for related indole-based anion re-
ceptors.[16f] Moreover, solid-state studies of phosphate com-
plexes crystallised from a DMSO/water mixture revealed
partial anion deprotonation upon complex crystallisation
(see below). Therefore, we performed some additional con-
À
trol titration experiments with H2PO4 and an excess of tri-
ACHTUNGTRENNUNGethylamine—a weak base, thus forming in principle a buf-
2À
fered solution of HPO4 anions. We found that also under
2À
À
these conditions with HPO4 anions, in analogy to H2PO4
anions, complexes of different stoichiometry are formed, the
abundance of which depends on the anion-to-receptor ratio
present in the solution.[34]
3À
In the case of titration of compounds 2 with HP2O7
anions, we observed slow (on the NMR time scale) equili-
bria between the free receptors and the complexes, as repre-
1
sented by the individual sets of signals in the H NMR spec-
tra (Figure 5). Interestingly, for all compounds, before reach-
ing the point of half an equivalent of the anion added, the
equilibrium is dominated by one complex, suggesting a com-
plex with a 2:1 receptor-to-anion stoichiometry, which was
also found in methanol solution (see below). Further anion
addition shifts the equilibrium towards another complex
with a 1:1 receptor-to-anion stoichiometry, analogically to
anions (Table 3). For all anions
except for the pyrophosphate,
the NMR titration data fit into
a 1:1 anion-to-receptor model,
and this stoichiometry of com-
plexes formed was further con-
firmed by the Job plots.[34] In
the case of HP2O73À, the strong
binding of the anion is appa-
rent and the Job plots indicate
that two molecules are bound
to one anionic species. Al-
though the 1:2 model offered
the best fit of all models tested
in the case of all three com-
pounds, the data gave a meth-
odologically satisfying fit only
for the compound 2b.
The association constants
determined for the different
NH protons are generally in
3À
Figure 5. 1H NMR spectra changes upon titration of receptor 2a with HP2O7 in [D6]DMSO/5% H2O.
&
6
&
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Highly Efficient and Selective Anion Receptors
FULL PAPER
erate preference for chloride over bromide, expressed by
these compounds, is uncommon.
The aliphatic derivative 2a and the phenyl derivative 2b
show similar selectivity for different anions, but with the
stronger anion binding by the later one, which plausibly
arises from the higher acidity of its urea protons. By analogy
to the auxiliary pyrrole moieties in the amide-based recep-
tor 1c, the introduction of two additional indole groups in
2c does not improve the affinity towards anions but does
moderate the selectivity, with the most considerable effect
À
in the case of HSO4 , whose binding becomes less favoura-
ble.
Next, to investigate the properties of the urea-based
building blocks 2 in anion binding systems of macrocyclic
topology, we obtained macrocycle 4 and compared its anion
affinity with the properties of its acyclic analogue, com-
pound 2a. The titration curves as well as the Job plots (see
the Supporting Information), recorded in DMSO/5% H2O,
revealed that the macrocyclic receptor tends to form 1:1 re-
ceptor-to-anion complexes with all anions studied, in con-
trast to receptor 2a (for pyrophosphate again at first the 2:1
receptor-to-anion complex is formed, but in the presence of
one and more equivalents of the anion the 1:1 complex is
dominant). Presumably, this stoichiometry results from the
lower conformational freedom, thus the pre-organised struc-
ture of the binding pocket. However, the compound can still
slightly interact with further equivalents of anions, making it
impossible to determine the association constants in this
medium. Subsequently, we tried to study compound 4 in
methanol solution, but after encountering solubility issues
here, we used a mixture of MeOH/20% DMSO. The results
show a significantly lower anion affinity of the macrocyclic
receptor 4 than that of its acyclic analogue 2a, with the asso-
ciation constants being around an order of magnitude lower
(Table 4). Moreover, in this solution, the relative selectivity
Figure 6. 1H NMR titration curves and Job plots of compound 2b with
À
À
À
À
different anions (N=HP2O73À
,
=H2PO4 , =PhCO2 , =Cl , =Br ,
~
&
*
^
hexagon=HSOÀ4 ) in [D3]MeOH. Chemical shifts of the indole NH group
(top) and one of the urea protons (bottom).
Table 3. Binding constants for the formation of 1:1 complexes of com-
pounds 2 with various anions in [D3]MeOH.[a]
Anion
Signal[b]
Ka [mÀ1
2b
]
2a
13
14
11
13
13
2c
26
ClÀ
indole
urea
indole
urea
indole
urea
37
31
29
23
28
21
22
15
39
–
235
265
–
BrÀ
À
PhCO2
[c]
[d]
15
28
À
H2PO4
indole
urea
125
135
–
360
535
–
À
[d]
[d]
[d]
NO3
–
À
HSO4
indole
urea
indole
97[e]
99[e]
235
280
78
90
–
is slightly altered for both the macrocyclic and the acyclic
À
receptors, with the most striking effect in the case of HSO4
whose binding becomes far less favourable.
,
3À
[f]
[f]
[f]
HP2O7
–
815 (1:1)[g]
10000 (2:1)
345 (1:1)[g]
12000 (2:1)
[f]
urea
–
–
Structural analysis studies: In the case of multifunctional
systems, which utilise anion binding for particular reasons,
the final properties of the pockets constructed from various
binding sites are derived from the geometrical parameters
and conformational preferences of the structural subunits
used, rather than from their binding-constant values. Thus,
understanding the anion binding on the molecular level is
crucial for the rational design of deliberate properties of
constructed systems. Therefore, we undertook systematic
studies to examine the conformational properties of the
studied diindolomethane-based building blocks, their bind-
ing modes and their coordination geometries.
[a] Values determined by 1H NMR titration experiments at T=298 K,
errors <10%, TBA salts were the source of the anions. [b] NH NMR
signal used for the calculations. [c] Value could not be determined due to
broadening and overlapping of the signals. [d] Interaction was too weak
to be measured. [e] Errors >10%. [f] Data cannot be fit to a simple 2:1
model; see the Supporting Information. [g] Values for the formation of
1:1 and 2:1 complexes, respectively.
good agreement. This suggests that both urea and indolyl
NH protons participate in anion anchoring similarly. The re-
sults show that compounds 2 clearly prefer tetrahedral ox-
oanions, because the strongest complexes are formed with
dihydrogen phosphate and hydrogen sulphate. Further ex-
amination of the relative selectivity for anions reveals un-
usual trends, with the most unexpected observation being
that compounds 2 bind halides as strongly as benzoate,
which is a much more basic anion. Moreover, the only mod-
Studies in the solid state: First, we obtained diffraction
grade crystals of the dinitro compound 6—the model of the
core unit of all of the receptors—by slow evaporation of a
solution of the compound in chloroform. Structural analysis
by X-ray crystallography reveals that the compound adopts
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
7
&
ÞÞ
These are not the final page numbers!

J. Jurczak et al.
Table 4. Binding constants for the formation of 1:1 complexes of com-
pounds 2a and 4 with various anions in a [D3]MeOH/20% [D6]DMSO
mixture.[a]
Anion
Signal[b]
Ka [mÀ1
]
4/2a
(Ka/Ka)
2a
13
13
–
14
21
4
ACHTUNGTRENNUNG
ClÀ
indole
urea
indole
urea
indole
urea
indole
urea
–
–
–
–
–
–
–
–
0.24
0.20
0.08
0.08
0.06
0.06
BrÀ
À
PhCO2
5
21
4[c]
À
H2PO4
330
340
50
25
27
3
À
HSO4
indole
urea
54
3
[a] Values determined by 1H NMR titration experiments at T=298 K,
errors <15%, TBA salts were the source of the anions. [b] NH NMR
signal used for the calculations. [c] Error >15%.
a bent sheet conformation, with the angle between the in-
dolyl planes, further referred to as a, being equal to 768
(Figure 7). Importantly, both NH groups point convergently
to the centre of the binding cleft. This result, together with
the absence of inter- and intramolecular hydrogen-bonding
interactions within the structure, suggests that this geometry
is preferred by this building block, and thus it is well pre-or-
ganised for interactions with a centrally positioned guest
molecule.
Figure 8. Crystal structure of compound 1a. Thermal ellipsoids are drawn
at the 50% probability level.
out of the indolyl planes (the torsion angles C6-C7-N(H)-
C(O) found are 6.8 and 25.78). Moreover, the indolyl
moieties are somewhat twisted with respect to each other,
so that the NH groups can interact with the carbonyl
oxygen atoms of the neighbouring receptor molecules locat-
À
ed above and below the receptor (the N O distances, refer-
red further as dNÀO, are in the range 2.81–2.93 ꢁ).
Slow evaporation of solution of the same compound (1a)
in DMSO resulted in the formation of different diffraction-
grade crystals, the structure of which was elucidated by X-
ray crystallography. It was shown that under these condi-
tions the compound crystallises as a DMSO-solvated adduct,
1a·DMSO, which is shown in Figure 9. Again, the receptor
molecule adopts a bent sheet shape (a=658) but only three
out of four NH groups are positioned convergently, forming
hydrogen-bonding interactions with the centrally located
oxygen atom of the DMSO molecule (dNÀO =2.79–3.10 ꢁ).
The fourth NH group, one of the amide groups, points out
of the pocket forming a hydrogen bond with the carbonyl
group of the neighbouring molecule (dNÀO =2.86 ꢁ). Thus,
the amide groups adopt a syn–anti conformation with the
torsion angles 36.1 and 129.08 for syn and anti, respectively.
The results for the free receptor 1a and for 1a·DMSO show
that the amide group can easily rotate and adjust the confor-
mation of the binding cleft to maximise the interactions
with the guest molecules or with the adjoining molecules.
Besides, the structure of the DMSO adduct shows that one
small guest molecule, like the single oxygen atom of the sol-
vent molecule, is unable to saturate all four NH groups of
the compounds 1.
Figure 7. Crystal structure of compound 6. Thermal ellipsoids are drawn
at the 50% probability level.
Next, we made a considerable effort to obtain diffraction-
grade crystals of the bisamide receptors 1 and 3, and of their
anion complexes. We were able to analyse the structures of
the following compounds: 1a, 1a·DMSO, 1b·H2O, 3·DMSO,
3·H2O·acetone, 1a·TBAPhCO2, 1c·TBACl and 3·TBABr.
Crystals of the free receptor 1a were grown by slow evap-
oration of a solution of the receptor in MeOH. The struc-
ture was elucidated by single-crystal X-ray diffraction and is
shown in Figure 8. The molecule, similarly to the dinitro de-
rivative 6, adopts a bent sheet conformation (a=748) in
which all four NH groups point convergently to the centre
of the binding pocket. Importantly, both amide groups
adopt a syn–syn conformation, but they are slightly tilted
This last conclusion can also be drawn from the structure
of a monohydrate of compound 1b, the crystals of which
were obtained by slow evaporation of a solution of the com-
pound in an acetone/water mixture. X-ray analysis reveals
that the compound again adopts a bent sheet conformation
&
8
&
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Highly Efficient and Selective Anion Receptors
FULL PAPER
Two different kinds of diffraction-grade crystals of the
macrocyclic compound 3 were grown by slow evaporation of
a solution of 3 in either DMSO or in a acetone/water mix-
ture, and both were elucidated by X-ray crystallography.
The two structures 3·DMSO and 3·H2O·acetone, which are
presented in Figures 11 and 12, present some similarities, de-
spite different co-crystallised solvent molecules. In the first
type of crystal, the DMSO molecule lies slightly above the
bent sheet-shaped molecule of the compound (a=708) and
forms two hydrogen bonds with one of the amidoindolyl
moieties (dNÀO =2.70–2.95 ꢁ), whereas the second amidoin-
dole group forms an intramolecular hydrogen bond between
the indolyl NH group and a carbonyl group (dNÀO =2.67–
2.71 ꢁ, the oxygen atom of the carbonyl is distorted be-
Figure 9. Crystal structure of compound 1a with DMSO. Thermal ellip-
soids are drawn at the 50% probability level.
(a=658) in which all NH groups point convergently to the
centre of the binding cleft, but only two of them—both in-
dolyl NH groups—form hydrogen bonds with a centrally
positioned water molecule (dNÀO =2.92 and 2.96 ꢁ,
Figure 10). The guest water molecule is situated in a way
that its hydrogen atoms are almost perpendicular to the
molecule and interact with the carbonyl groups of neigh-
bouring molecules, bridging every third molecule of the re-
ceptor (dOÀO =2.74 and 2.80 ꢁ). Notably, the phenyl rings
À
contribute to the binding of water through CH O interac-
tions (dCH O =2.65 and 2.74 ꢁ). Each two molecules form a
À
centrosymmetric dimer stabilised by a pair of hydrogen
bonds formed between the amide groups (dNÀO =3.06 ꢁ), re-
sulting in torsion angles for the amide groups of 29.6 and
30.68.
Figure 11. Crystal structure of compound 3 with DMSO, alternative posi-
tions of DMSO are omitted for clarity, for more information see the Sup-
porting Information. Thermal ellipsoids are drawn at the 50% probabili-
ty level.
Figure 10. Crystal structure of compound 1b with water. Thermal ellip-
Figure 12. Crystal structure of the solvate of compound 3 with acetone
soids are drawn at the 50% probability level.
and water. Thermal ellipsoids are drawn at the 50% probability level.
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
9
&
ÞÞ
These are not the final page numbers!

J. Jurczak et al.
tween two positions). Thus, the amide groups adopt a syn–
anti conformation (the torsion angles for the amide groups
being 39.9 and 174.68, respectively), and the later NH group
pointing outwards from the binding cleft can weakly interact
with the carbonyl group of the adjoining receptor molecule
(dNÀO =2.96 ꢁ).
On the other hand, the results of the X-ray analysis of the
second type of crystal show that the independent part of the
structure contains two adducts of 3·H2O·acetone, differing
only slightly in the conformation, which stay similar to the
3·DMSO geometry (Figure 12). The compounds again have
a bent sheet shape (a=66 and 718) with convergently posi-
tioned indolyl NH groups. In these cases, the previous posi-
tion of the DMSO molecule is occupied by a water mole-
cule, which accepts one hydrogen bond from an indolyl NH
group (dNÀO =2.84 and 2.85 ꢁ) and donates two hydrogen
bonds: one to the carbonyl group of the amide group on the
other indolyl moiety and the other to the carbonyl oxygen
atom of the above-laying receptor molecule (dNÀO =2.71–
2.91 and 2.73–2.80 ꢁ, respectively). As before, one of the
amide groups accepts the anti conformation, which is stabi-
lised by the intramolecular interaction of CO with the indol-
yl NH group (dNÀO =2.67–2.74 ꢁ) and by the aforemen-
tioned interaction with the water molecule, as well as by the
interaction of NH with the carbonyl group of the externally
positioned acetone molecule (dNÀO =2.93–2.94 ꢁ). The
second amide group is highly tilted out of the indolyl plane
(a=67–688), this conformation of which is stabilised by in-
teractions with the equivalent amide groups of the neigh-
bouring receptor molecules lying above and below the re-
ceptor (dNÀO =2.94-3.03 ꢁ).
Figure 13. Crystal structure of the benzoate complex of compound 1a.
Thermal ellipsoids are drawn at the 50% probability level.
Slow evaporation of a solution of compound 1a in DMSO
in the presence of tetrabutylammonium benzoate gave crys-
tals of the complex 1a·TBAPhCO2. X-ray crystallographic
analysis reveals that the independent part of the structure
contains two complexes of very similar geometry. In both
cases, the receptor adopts a bent sheet conformation (a=
638) and binds benzoate with all four NH groups, as shown
in Figure 13. The anion is located almost centrally above the
receptor with its phenyl ring pointing outwards. Each
oxygen atom of the carboxylate forms two hydrogen bonds
with the indolyl and amide NH groups, but one pair of
bonds is somewhat shorter than the other one, thus the
anion is slightly tilted. Judging by the bond lengths, the in-
dolyl NH groups interact with the anion more strongly than
the amide groups (dNÀO =2.72–2.82 ꢁ for the indoles and
2.86–2.91 ꢁ for the amides, respectively), this observation is
in agreement with the results of the titration experiments.
Crystals of the chloride complex of receptor 1c, in turn,
were grown by slow diffusion of pentane to a solution of the
receptor in C2H4Cl2 and ethyl acetate in the presence of
TBA chloride. Also in this case, the crystal structure consists
of two independent complexes that differ slightly in the con-
formation of the receptor. As shown in Figure 14, the chlor-
ide anion perches over the bent sheet-shaped receptor mole-
cule (a=668) being bound by four NH groups of the
pocket. The hydrogen bonds formed by the indole NH
Figure 14. Crystal structure of the chloride complex of compound 1c.
Thermal ellipsoids are drawn at the 50% probability level.
groups are clearly stronger than the ones engaging the
amide groups (dNÀCl =3.11–3.27 ꢁ for the former ones and
3.40–3.70 ꢁ for the latter ones), showing the host–guest size
mismatch. Interestingly, both additional amidopyrrole sub-
AHCTUNGTREGuNNNU nits adopt a anti conformation, which preclude them from
taking part in the anion binding. This observation is in
agreement with the results of the titration experiments.
However, the pyrrole rings form intermolecular hydrogen
bonds, but with carbonyl groups of adjoining molecules
(dNÀOꢀ2.8 ꢁ), which leads to the formation of supramolecu-
lar chains made of chloride–receptor complexes linked to-
gether.
Finally, crystals of the bromide complex of the macrocy-
clic compound 3 were obtained, when a solution of the re-
ceptor in DMSO in the presence of tetrabutylammonium
&
10
&
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Highly Efficient and Selective Anion Receptors
FULL PAPER
bromide was slowly evaporated. The structure was elucidat-
ed by X-ray crystallography, revealing that again the inde-
pendent part consists of two very similar 3·BrÀ complexes,
one of which is presented in Figure 15. Like in the chloride
complexes of 1c, the bromide anion perches over the bent
hosts 2a, 2c and 4, as well as of the phosphate complexes of
2b and 2c. In all cases, diffraction-grade crystals were ob-
tained by slow evaporation of a solution of the compound in
DMSO, but in the presence of an excess of tetrabutylammo-
nium dihydrogen phosphate for the anion complexes.
X-ray analysis of the single crystal of the free host 2a re-
veals that the receptor crystallises as a DMSO adduct,
2a·DMSO, the structure of which closely resembles the crys-
tal structure of its amide analogue, 1a·DMSO. Like before,
the receptor adopts a bent sheet shape (a=668) with a syn–
anti conformation of the side groups (the torsion angles
being 30 and 1348, respectively, as shown in Figure 16). This
Figure 15. Crystal structure of the bromide complex of compound 3.
Thermal ellipsoids are drawn at the 50% probability level.
sheet-shape receptor molecule 3 (a=61 and 678) and is
anchored by four hydrogen bonds stemming from the
pocket. Judging by the bond lengths, again the indolyl NH
groups bind the anion more strongly than the amide groups
(dNÀBr =3.32–3.42 ꢁ for the indolyl NH groups and 3.52–
3.61 ꢁ for the amide NH groups),[35] but in this case the geo-
metrical mismatch is significantly smaller than for the chlor-
ide anions, presumably due to the larger size of the bromide
guest molecule. Notably, the compound adopts a syn–syn
conformation in the complex, which is the most favourable
for the anion binding, despite the fact that the free receptor
was found to stay in a syn–anti conformation in the cases of
both 3·H2O·acetone and 3·DMSO solvent adducts (Fig-
ures 11 and 12).
Remarkably, in all of these eight crystal structures, the
amide-functionalised receptors 1 and 3 adopt similar bent
sheet conformations despite the different host side chains
and different guest molecules. The amide moieties in the
free receptor tend to point convergently to the centre of the
binding cleft, but in some cases one of them is tiled out to
maximise the interactions with the adjoining molecules. No-
tably, in all three anion complexes they adopt a syn–syn con-
formation and interact with the centrally positioned anionic
guest species. The results suggest that this geometry is pre-
ferred by this building block, and its binding site is readily
available for interactions involving all four hydrogen-bond
donors.
Figure 16. Crystal structure of compound 2a with DMSO; alternative po-
sitions of DMSO are omitted for clarity, for more information see the
Supporting Information. Thermal ellipsoids are drawn at the 50% proba-
bility level.
orientation of the urea groups allows the formation of four
strong intermolecular hydrogen bonds, forming two “urea
bridges”, with adjoining receptor molecules (dNÀO =2.850–
2.96 ꢁ). Like in the case of 1a·DMSO, two out of four con-
vergent hydrogen-bond donors (one of the indole NH
groups and the neighbouring urea NH group) bind to the
oxygen atom of the centrally positioned DMSO molecule
(dNÀO =2.63–2.93 ꢁ).
In turn, the crystallographic analysis of 2c reveals that,
under the conditions used, the free receptor crystallises as a
solvent adduct with two molecules of DMSO, as shown in
Figures 17 and 18. The crystal structure also contains a third
DMSO molecule, but it does not interact with the receptor
through hydrogen bonding. Again, the core unit of the re-
ceptor—diindolomethane—adopts a bent sheet shape (a=
578) with a syn–anti conformation of the side urea groups.
However, the indolyl moieties are somewhat twisted with
respect to each other, so that both side idolylurea moieties
Next, we focused our attention on the bisurea receptors 2
and 4. We were able to grow and analyse crystals of the free
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
11
&
ÞÞ
These are not the final page numbers!

J. Jurczak et al.
group of the anti urea functionality of the adjoining receptor
molecule (dNÀO =2.79 ꢁ). The outermost NH group of this
functionality binds to the carbonyl oxygen atom of the
neighbouring receptor (dNÀO =2.89 ꢁ). The structure shows
that compound 2c is very flexible and able to adopt a con-
formation, which allows for the maximal number and high
strength of the intra- and intermolecular hydrogen-bonding
interactions.
In the case of crystals of the macrocyclic compound 4,
X-ray analysis reveals that the independent part of the
structure contains three solvent adducts, 4·ACTHNURGTNEUNG(DMSO)2, of very
similar geometry. In all cases, the receptor adopts a bent
sheet shape (a=76–818), but with an anti–anti conformation
of its urea functionalities, as is shown in Figure 19. This ge-
Figure 17. Crystal structure of 2c with DMSO; a part of adjoining recep-
tor molecule is depicted (lightened) to show intermolecular interactions,
for more information see the Supporting Information. Thermal ellipsoids
are drawn at the 50% probability level.
Figure 19. Crystal structure of 4 with DMSO, alternative positions of
DMSO omitted for clarity, for more information see the Supporting In-
formation. Thermal ellipsoids are drawn at the 50% probability level.
Figure 18. Crystal structure of 2a with DMSO; a part of adjoining recep-
tor molecule is depicted (lightened) to show intermolecular interac-
tions—an alternative view, with some hydrogen atoms omitted for clarity,
for more information see the Supporting Information. Thermal ellipsoids
are drawn at the 50% probability level.
ometry is stabilised by two strong intramolecular hydrogen
bonds between the indolyl NH groups and the carbonyl
groups of the urea moieties (dNÀO =2.65–2.79 ꢁ). Moreover,
the urea NH groups form four intermolecular hydrogen
bonds, two of them by one urea functionality with the car-
can be positioned above and below, respectively. Conse-
quently, the whole receptor molecule adopts a helical shape
conformation (Figures 17 and 18), and this geometry is sta-
bilised by the hydrogen bond between the carbonyl group of
the anti urea moiety and the innermost NH group of the syn
urea moiety (dNÀO =2.90 ꢁ), as well as by two hydrogen
bonds stemming from two indolyl NH groups, one of the
pendant and one of the core indole moieties, with the bridg-
ing DMSO molecule (dNÀO =2.82–2.89 ꢁ). The second indol-
yl NH group interacts with the second DMSO molecule
(dNÀO=2.88 ꢁ), which is also bound with the innermost NH
bonyl group of the neighbouring receptor molecule (dNÀ =
O
2.84–3.02 ꢁ) and the other two by the second urea with two
DMSO solvent molecules (dNÀO =2.75–2.91 ꢁ). This struc-
ture suggests that the macrocyclic topology of 4, rather than
promoting anion binding by the restricted flexibility of the
receptor, instead hampers the adoption of the conformation
appropriate for interactions with the centrally positioned
anionic species. This observation is in agreement with the
solution binding studies, which showed deteriorated anion
affinity of macrocyclic 4 in respect to its acyclic analogue
2a. One possible clearance of this obstacle would be to use
&
12
&
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Highly Efficient and Selective Anion Receptors
FULL PAPER
a longer aliphatic linker, which introduces more flexibility
to the receptor molecule.
X-ray analysis of the phosphate complex of receptor 2c
reveals that the anion undergoes deprotonation upon crys-
tallisation and the actual complex is formed with HPO42À. A
similar phenomenon of anion deprotonation upon crystalli-
sation has already been observed by Gale and co-workers
for related indole-based compounds.[16d–f,17d] As shown in
Figure 20, the diindolylmethane scaffold of 2c adopts a bent
sheet shape (a=788) with a syn–syn conformation of the
side arms. Importantly, all NH groups point convergently to
the centre of the binding pocket and form hydrogen bonds
with the oxygen atoms of the centrally positioned anion
molecule. Judging by the lengths of the hydrogen bonds
formed, the indole NH groups bind the anion more strongly
than the urea NH groups (dNÀO =2.76–2.85 and 2.74–3.08 ꢁ,
respectively). Consequently, the structure shows that recep-
tor 2c is capable of binding tetrahedral anions, like phos-
phates and sulphates, with eight complementary hydrogen
bonds. Moreover, comparison of the structure of the free re-
ceptor and of its phosphate complex shows that the confor-
mation of the receptor is flexible and can be adjusted to the
guest molecule.
Figure 20. Crystal structure of the hydrogenphosphate complex of recep-
tor 2c. Thermal ellipsoids are drawn at the 50% probability level.
In turn, X-ray analysis of the phosphate complex of 2b re-
veals that the complex formed has the unusual stoichiometry
of 2b2·TBA3H
(PO4)2. The actual complex formed is a su-
ly different hydrogen-bond pattern is observed than in the
case of the complex of 2c (Figure 20). Interestingly, the con-
formation of compound 2b adopted in this complex is simi-
lar to the one of the complex of 2c, which suggests that it is
the preferred geometry for this class of receptors.
pramolecule, which can be described as a 2:1 complex be-
tween two molecules of compound 2b and an unusual phos-
phate dimer—[H3PO4·PO4]3À—as is shown in Figures 21 and
22. It appears that upon crystallisation, two phosphate
anions are deprotonated, brought together and bridged by
three protons, and this “supra-anion” formed is stabilised by
interactions with two molecules of 2b. Both tetrahedral
phosphonic subunits are in
Interestingly, in all five crystal structures of the free bis-
AHCTUNGTRENNUNG
close proximity, resulting in a
À
P P distance of 3.68 ꢁ. To the
best of our knowledge there is
no precedent of any similar
phosphate dimer in the litera-
ture.
However, the CSD and ICSD
databases do contain structures
of phosphate anions joined by
one or two hydrogen bonds,
thus resulting in a significantly
larger distance between the
phosphorous atoms (around
4.1–4.2 ꢁ). Further analysis of
the structure reveals that the
receptor adopts a bent sheet
geometry (a=648) with a syn–
syn conformation of the urea
moieties. Importantly, all six
NH protons are convergent
and are involved in interac-
tions with the anions (dNÀ
=
O
2.71–3.12 ꢁ), although a slight-
Figure 21. Crystal structure of 2b2·TBA3H3ACTHUNGTERNU(NG PO4)2. Thermal ellipsoids are drawn at the 50% probability level.
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
13
&
ÞÞ
These are not the final page numbers!

J. Jurczak et al.
the population of the syn–syn conformer is greatly enriched,
which is in agreement with the solid-state structure of the
benzoate complex of 1a (Figure 16).
By analogy to the results for 1a, the studies for the mac-
rocyclic analogue 3 show that in the absence of an anion the
receptor is in equilibrium between syn–syn, syn–anti and
anti–anti conformers. However, upon anion addition the
syn–syn conformation seems to become dominant. We ob-
served a similar trend in the solid state: the free receptor 3
crystallises in a syn–anti conformation (Figures 14 and 15),
whereas in the bromide complex compound 3 adopts a syn–
syn conformation, which allows for the best interactions
with the centrally positioned guest molecule (Figure 18).
Like in the case of 1a, the free urea-based compound 2a
exists in solution in a mixture of conformations with the syn
and anti conformation of the urea moieties (in the solid
state 2a adopts a syn–anti geometry, Figure 19). However,
the presence of benzoate anions again shifts the conforma-
tional equilibrium of compound 2a towards a higher popula-
tion of the syn conformer, which can interact more strongly
with the anionic guests.
Figure 22. Crystal structure of 2b2·TBA3H3ACTHNUTGRNEG(UN PO4)2—the half of the dimer.
Thermal ellipsoids are drawn at the 50% probability level.
Interestingly, there is only a relatively weak ROE be-
tween the indole NH group and the intermost urea NH
group for the macrocyclic analogue 4, which was observed
in the solid state in the anti–anti conformer (Figure 22).
Moreover, the presence of anions does not affect the ROE,
hence suggesting that even in the presence of anions com-
pound 4 mostly exists as the anti–anti conformer unfavoura-
ble for anion binding. These results explain the relatively
low affinity of 4 towards anionic species, in contrast to the
anion complexation properties of its acyclic analogue 2a
(Table 4).
Consequently, the studies in solution were in agreement
with the findings in the solid state, showing that the side
arms, the amide or urea moieties, in compounds 1–3 can
easily adopt both syn and anti conformations. However, the
presence of anions induces the conformational change to
the syn–syn geometry, which allows for interactions of all
hydrogen bonding NH groups with the centrally located
anionic guest. Compound 4 seems not to be able to adopt a
syn–syn conformation, presumably due to the fact that the
size of the macrocycle is too small, hence resulting in its low
anion affinity.
fold is in a very similar bent sheet conformation. However,
in the case of the free receptors, the urea groups tend to tilt
out of the pocket so that they can form hydrogen-bonding
interactions with neighbouring molecules; importantly, in
the anion complexes, they point convergently to the centre,
binding strongly to the anionic guest. These results show
that the bisurea-functionalised diindolylmethane moiety is a
readily available building block for efficient anion binding
pockets, which provides six hydrogen-bonding groups for
the strong anchoring of the centrally located anionic species.
Studies in solution: The crystal structure studies of receptors
1–4 show that they adopt the bent sheet shape conformation
appropriate for anion binding, but the position of the amide
or urea group is highly dependent on the guests (anion or
solvent molecule) present in the crystal structure, or on the
position of the neighbouring receptor molecules. Thus, to
gain insight into their conformational preferences in solu-
tion, we performed a series of ROESY experiments for se-
lected receptors in the absence and the presence of anionic
guests. The experiments for the free receptor 1a revealed
the ROE (nuclear Overhauser effect in the rotating frame)
of the amide NH with the indole NH as well as with the
neighbouring aromatic C(6)H. Thus, in solution the amide
groups of 1a adopt both syn and anti conformations, which
are in fast equilibrium between each other. This observation
is in agreement with the solid-state findings, which revealed
a syn–syn and a syn–anti conformers of 1a (Figures 11 and
12, respectively), depending on the crystallisation conditions.
Importantly, upon addition of TBA benzoate to a solution
of 1a the recorded interaction of the amide NH group with
the indole NH group is considerably amplified, whereas its
interaction with the aromatic C(6)H is diminished. Hence,
Conclusion
We have introduced 7,7’-diamino-2,2’-diindolylmethane (7)
as an easy-to-make building block for anion receptors oper-
ating with hydrogen bonds. Acyclic bisamide derivatives of
7, that is, compounds 1, show remarkably high anion affini-
ties, with exceptional selectivity towards dihydrogen phos-
phate. This anion is bound even in such polar and competi-
tive media as DMSO with 25% H2O or pure methanol.
Control titration experiments with compound 6, which lacks
the side amide groups, confirmed the crucial role of the con-
certed anion binding with both amide and indole groups in
&
14
&
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Highly Efficient and Selective Anion Receptors
FULL PAPER
[3] P. A. Gale, T. Gunnlaugsson, Chem. Soc. Rev. 2010, 39, 3595–3596.
[4] a) C. Bazzicalupi, A. Bencini, V. Lippolis, Chem. Soc. Rev. 2010, 39,
3709–3728; b) P. Ballester, Chem. Soc. Rev. 2010, 39, 3810–3830;
c) S.-O. Kang, J. M. Llinares, V. W. Day, K. Bowman-James, Chem.
Soc. Rev. 2010, 39, 3980–4003; d) K. Wichmann, B. Antonioli, T.
Soehnel, M. Wenzel, K. Gloe, K. Gloe, J. R. Price, L. F. Lindoy, A. J.
Blake, M. Schroeder, Coord. Chem. Rev. 2006, 250, 2987–3003.
[5] a) J. W. Steed, Chem. Soc. Rev. 2009, 38, 506–519; b) D. J. Mercer,
S. J. Loeb, Chem. Soc. Rev. 2010, 39, 3612–3620.
the pocket of compounds 1. Conformational studies of the
free receptors 1 and their anion complexes show that the
bisamides 1 can easily adopt a syn–syn conformation, which
allows for optimal interactions of all four hydrogen-bond
donors with the centrally positioned anionic guest. Studies
of the macrocyclic analogue 3, which possesses comparable
anion binding properties, further suggest that the acyclic
compounds 1 have a favourable conformation and thus
cannot benefit from the macrocyclic effect.
[6] a) E. Galbraith, T. D. James, Chem. Soc. Rev. 2010, 39, 3831–3842;
b) H. E. Katz, J. Am. Chem. Soc. 1985, 107, 1420–1421; c) H. E.
Katz, J. Org. Chem. 1985, 50, 5027–5032.
Acyclic bisurea derivatives of 7, that is, receptors 2, exhib-
it even higher affinities towards anions than their amide an-
alogues, and are selective towards tetrahedral oxoanions,
that is, dihydrogen phosphate and hydrogen sulphate. Hy-
drogen pyrrophosphate is also strongly bound by these
hosts, but it forms complexes of different stoichiometry. No-
tably, compounds 2 form complexes with anions even in
methanol—a very demanding, competitive and protic sol-
vent. The studies in solution and in the solid state revealed
that in the presence of anionic species the binding pocket of
2 adopts a syn–syn conformation, which is suitable for anion
anchoring with all the six hydrogen-bond NH donors and
leads to strong anion binding. In the contrast to its acyclic
analogues, the macrocycle 4 does not assume a syn–syn con-
formation presumably due to the small size of the macrocy-
clic ring, which is reflected in its poor anion binding proper-
ties.
[7] a) B. L. Schottel, H. T. Chifotides, K. R. Dunbar, Chem. Soc. Rev.
2008, 37, 68–83; b) B. P. Hay, R. Custelcean, Cryst. Growth Des.
2009, 9, 2539–2545; c) G. Gil-Ramꢂrez, J. Benet-Buchholz, E. C. Es-
cudero-Adan, P. Ballester, J. Am. Chem. Soc. 2007, 129, 3820–3821;
d) G. Gil-Ramꢂrez, E. C. Escudero-Adan, J. Benet-Buchholz, P. Bal-
lester, Angew. Chem. 2008, 120, 4182–4186; Angew. Chem. Int. Ed.
2008, 47, 4114–4118.
[8] a) Y. Inoue, T. Hakushi, Y. Liu, L. Tong, B. Shen, D. Jin, J. Am.
Chem. Soc. 1993, 115, 475–481; b) J. W. Steed, R. K. Juneja, J. L.
Atwood, Angew. Chem. 1994, 106, 2571–2573; Angew. Chem. Int.
Ed. Engl. 1994, 33, 2456–2457.
[9] a) S. O. Kang, R. A. Begum, K. Bowmna-James, Angew. Chem.
2006, 118, 8048–8061; Angew. Chem. Int. Ed. 2006, 45, 7882–7894;
b) P. A. Gale, Acc. Chem. Res. 2006, 39, 465–475; c) A.-F. Li, J.-H.
Wang, F. Wang, Y.-B. Jiang, Chem. Soc. Rev. 2010, 39, 3729–3745.
[10] a) C. Caltagirone, P. A. Gale, Chem. Soc. Rev. 2009, 38, 520–563;
b) P. A. Gale, S. E. Garcia-Garrido, J. Garric, Chem. Soc. Rev. 2008,
37, 151–190; c) P. A. Gale, Chem. Soc. Rev. 2010, 39, 3746–3771;
d) M. Wenzel, J. R. Hiscock, P. A. Gale, Chem. Soc. Rev. 2012, 41,
480–520.
We would like to mention that 7,7’-diamino-2,2’-diindolyl-
methane has recently been applied in the construction of
very selective transition-metal catalysts.[22] The interaction
between the anionic substrate and the anion binding pocket
built into the rhodium catalyst made it possible to control
the regioselectivity of the hydroformylation reaction;[22a] in
another study the pocket was found to bind an anionic
chiral cofactors, which lead to highly enantioselective cata-
lysts for the hydrogenation of olefins.[22b]
To summarise, bisamine 7 is an easy-to-make precursor
for very efficient anion binding receptors, operating also in
protic media, thus it has promising potential for practical ap-
plications. Moreover, we believe that our comprehensive in-
vestigation of the simple receptors based on this new build-
ing block, particularly of the relationship between anion
binding and the structural properties, should help in the
design and preparation of more advanced and efficient sys-
tems.
[11] a) H. Luecke, F. A. Quiocho, Nature 1990, 347, 402–406; b) B. L. Ja-
cobson, F. A. Quiocho, J. Mol. Biol. 1988, 204, 783–787; c) J. W.
Pflugrath, F. A. Quiocho, Nature 1985, 314, 257–260.
[12] G. V. Oshovsky, D. N. Reinhoudt, W. Verboom, Angew. Chem. 2007,
119, 2418–2445; Angew. Chem. Int. Ed. 2007, 46, 2366–2393.
[13] a) S. Kubik, Chem. Soc. Rev. 2010, 39, 3648–3663; b) S. Kubik, C.
Reyheller, S. Stuewe, J. Inclusion Phenom. Macrocyclic Chem. 2005,
52, 137–187; c) S. Kubik, Chem. Soc. Rev. 2009, 38, 585–605.
[14] a) C. Reyheller, S. Kubik, Org. Lett. 2007, 9, 5271–5274; b) S.
Kubik, R. Goddard, S. Otto, S. Pohl, C. Reyheller, S. Stuewe, Bio-
sens. Bioelectron. 2005, 20, 2364–2375; c) S. Kubik, R. Kirchner, D.
Nolting, J. Seidel, J. Am. Chem. Soc. 2002, 124, 12752–12760; d) J.-
m. Suk, K.-S. Jeong, J. Am. Chem. Soc. 2008, 130, 11868–11869;
e) N.-K. Kim, K.-J. Chang, D. Moon, M. S. Lah, K.-S. Jeong, Chem.
Commun. 2007, 3401–3403; f) U.-I. Kim, J.-M. Suk, V. R. Naidu, K.-
S. Jeong, Chem. Eur. J. 2008, 14, 11406–11414.
[15] a) P. Dydio, D. Lichosyt, J. Jurczak, Chem. Soc. Rev. 2011, 40, 2971–
2985; b) J. Jurczak, M. J. Chmielewski, P. Dydio, D. Lichosyt, F. Ula-
´
towski, T. Zielinski, Pure Appl. Chem. 2011, 83, 1543–1554.
[16] a) I. E. D. Vega, S. Camiolo, P. A. Gale, M. B. Hursthouse, M. E.
Light, Chem. Commun. 2003, 1686–1687; b) I. E. D. Vega, P. A.
Gale, M. B. Hursthouse, M. E. Light, Org. Biomol. Chem. 2004, 2,
2935–2941; c) D. Curiel, A. Espinosa, M. Mas-Montoya, G. Sanchez,
A. Tarraga, P. Molina, Chem. Commun. 2009, 7539–7541; d) C. Cal-
tagirone, P. A. Gale, J. R. Hiscock, S. J. Brooks, M. B. Hursthouse,
M. E. Light, Chem. Commun. 2008, 3007–3009; e) C. Caltagirone,
J. R. Hiscock, M. B. Hursthouse, M. E. Light, P. A. Gale, Chem. Eur.
J. 2008, 14, 10236–10243; f) P. A. Gale, J. R. Hiscock, S. J. Moore, C.
Caltagirone, M. B. Hursthouse, M. E. Light, Chem. Asian J. 2010, 5,
555–561.
Acknowledgements
We would like to acknowledge the Polish Ministry of Science and Higher
Education for financial support of this work (Project N N204 092735),
Dr. Ł. Dobrzycki and M. Stachowicz for the crystallographic measure-
ments, Dr. P. Cmoch and Dr. O. Staszewska-Krajewska for assistance
with the ROESY experiments and Ł. Sobczak for fruitful discussions.
[17] a) G. W. Bates, P. A. Gale, M. E. Light, Chem. Commun. 2007,
´
2121–2123; b) T. Zielinski, P. Dydio, J. Jurczak, Tetrahedron 2008,
64, 568–574; c) C. Caltagirone, A. Mulas, F. Isaia, V. Lippolis, P. A.
Gale, M. E. Light, Chem. Commun. 2009, 6279–6281; d) P. A. Gale,
J. R. Hiscock, C. Z. Jie, M. B. Hursthouse, M. E. Light, Chem. Sci.
2010, 1, 215–220; e) J. R. Hiscock, P. A. Gale, M. J. Hynes, Supra-
mol. Chem. 2012, 24, 355–360.
[1] Supramolecular Chemistry, 2nd ed. (Eds.: J. W. Steed, J. L. Atwood),
Wiley, New York, 2009.
[2] J. L. Sessler, P. A. Gale, W.-S. Cho, Anion Receptor Chemistry, RSC,
London, 2006.
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
15
&
ÞÞ
These are not the final page numbers!

J. Jurczak et al.
[18] a) J. R. Hiscock, C. Caltagirone, M. E. Light, M. B. Hursthouse,
P. A. Gale, Org. Biomol. Chem. 2009, 7, 1781–1783; b) J. R. His-
cock, P. A. Gale, C. Caltagirone, M. B. Hursthouse, M. E. Light, Su-
pramol. Chem. 2010, 22, 647–652.
[26] L. Fielding, Tetrahedron 2000, 56, 6151–6170.
[27] P. Job, Ann. Chim. Appl. 1928, 9, 113–203.
[28] M. J. Chmielewski, M. Charon, J. Jurczak, Org. Lett. 2004, 6, 3501–
3504.
´
[19] a) N. J. Andrews, C. J. E. Haynes, M. E. Light, S. J. Moore, C. C.
Tong, J. T. Davis, W. A. Harrell, Jr., P. A. Gale, Chem. Sci. 2011, 2,
256–260; b) S. J. Moore, M. Wenzel, M. E. Light, R. Morley, S. J.
Bradberry, P. Gꢃmez-Iglesias, V. Soto-Cerrato, R. Pꢄrez-Tomꢅs,
P. A. Gale, Chem. Sci. 2012, 3, 2501–2509.
[29] a) T. Zielinski, J. Jurczak, Tetrahedron 2005, 61, 4081–4089; b) P. V.
Santacroce, J. T. Davis, M. E. Light, P. A. Gale, J. C. Iglesias-San-
chez, P. Prados, R. Quesada, J. Am. Chem. Soc. 2007, 129, 1886–
1887; c) M. J. Chmielewski, J. Jurczak, Chem. Eur. J. 2006, 12, 7652–
7667; d) D. Makuc, M. Lenarcic, G. W. Bates, P. A. Gale, J. Plavec,
Org. Biomol. Chem. 2009, 7, 3505–3511; e) D. Makuc, Triyanti, M.
Albrecht, J. Plavec, K. Rissanen, A. Valkonen, C. A. Schalley, Eur.
J. Org. Chem. 2009, 4854–4866.
[20] G. W. Bates, Triyanti, M. E. Light, M. Albrecht, P. A. Gale, J. Org.
Chem. 2007, 72, 8921–8927.
´
[21] a) P. Dydio, T. Zielinski, J. Jurczak, Chem. Commun. 2009, 4560–
´
4562; b) P. Dydio, T. Zielinski, J. Jurczak, Org. Lett. 2010, 12, 1076–
1078.
[30] a) W. Oi, M. Nishiki, K. Ito, Lett. Org. Chem. 2007, 4, 112–119;
b) M. Nishiki, W. Oi, K. Ito, J. Inclusion Phenom. Macrocyclic
Chem. 2008, 61, 61–69; c) J. L. Sessler, D. An, W.-S. Cho, V. Lynch,
M. Marquez, Chem. Eur. J. 2005, 11, 2001–2011.
[22] a) P. Dydio, W. I. Dzik, M. Lutz, B. de Bruin. J. N. H. Reek, Angew.
Chem. 2011, 123, 416–420; Angew. Chem. Int. Ed. 2011, 50, 396–
400; b) P. Dydio, C. Rubay, T. Gadzikwa, M. Lutz, J. N. H. Reek, J.
Am. Chem. Soc. 2011, 133, 17176–17179.
[23] G. Penieres-Carrillo, J. G. Garcia-Estrada, J. L. Gutierrez-Ramirez,
C. Alvarez-Toledano, Green Chem. 2003, 5, 337–339.
[31] D. Hꢆr, A. Gꢆven, THEOCHEM 2002, 583, 1–18.
À
[32] In [D6]acetone, compound 6 interacts with PhCO2 forming com-
plexes with an association constant of Ka =90mÀ1, whereas with
À
H2PO4 the NH signal broadening and disappearance was observed.
[24] Obtained in this way, 3,3’- diindolylmethanes were studied as colori-
metric anion sensors, see: X. M. He, S. Z. Hu, K. Liu, Y. Guo, J. Xu,
S. J. Shao, Org. Lett. 2006, 8, 333–336.
[25] a) V. Amendola, D. Esteban-Gꢃmez, L. Fabbrizzi, M. Licchelli, Acc.
Chem. Res. 2006, 39, 343–353; b) D. Esteban-Gꢃmez, L. Fabbrizzi,
M. Licchelli, J. Org. Chem. 2005, 70, 5717–5720; c) M. Boiocchi,
B. L. Del, D. Esteban-Gꢃmez, L. Fabbrizzi, M. Licchelli, E. Monza-
ni, Chem. Eur. J. 2005, 11, 3097–3104; d) P. Dydio, T. Zielinski, J.
Jurczak, J. Org. Chem. 2009, 74, 1525–1530.
[33] M. J. Chmielewski, J. Jurczak, Chem. Eur. J. 2005, 11, 6080–6094.
[34] For details see the Supporting Information.
[35] The hydrogen bonds for the bromide complexes are longer than for
the chloride complexes due to the significantly higher size of the
former one.
Received: July 16, 2012
Published online: && &&, 0000
&
16
&
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Highly Efficient and Selective Anion Receptors
FULL PAPER
One to catch them all! A series of
amide and urea derivatives of 7,7’-di-
Host–Guest Systems
ACHTUNGTRENNUNGamino-2,2’-diindolylmethane (DIM)
´
P. Dydio, D. Lichosyt, T. Zielinski,
that can recognise various anions
through hydrogen bonding even in
very demanding solvents (DMSO/
water, methanol), has been prepared.
The efficiency and selectivity of these
receptors depends on the side groups
introduced and their conformational
preferences. The binding mode for dif-
ferent anions is demonstrated by X-ray
crystallography (see figure).
J. Jurczak* ..................... &&&& — &&&&
7,7’-Diamino-2,2’-diindolylmethane: A
Building Block for Highly Efficient
and Selective Anion Receptors—
Studies in Solution and in the Solid
State
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
17
&
ÞÞ
These are not the final page numbers!