Non-symmetric substituted ureas locked in an (E,Z) conformation: An unusual anion binding via supramolecular assembly

Article abstract of DOI:10.1039/c2nj40877e

Two new asymmetric ureidic receptors L¹ (1-(1H-indol-7-yl)-3- (quinolin-2-yl)urea) and L² (1-(quinolin-2-yl)-3-(quinolin-8-yl)urea) have been synthesised and their affinity towards different anions tested in DMSO-d₆. L¹ adopts both in solution and in the solid state an (E,Z) conformation. A moderate affinity for acetate has been observed for L¹ while no interaction has been observed for L². The different behaviour has been ascribed to the presence/absence of the indole group. In the case of L¹ the indole group causes the formation of a peculiar supramolecular architecture with two molecules of the receptor binding the anions in the (E,Z) conformation via H-bonds. L² also adopts an (E,Z) conformation in the solid state. However, the absence of the indole group in L² hampers the formation of the supramolecular assembly with the participation of anionic species.

Full text of DOI:10.1039/c2nj40877e

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Non-symmetric substituted ureas locked in (E,Z) conformation: an
unusual anion binding via supramolecular assembly
Martina Olivari,a Claudia Caltagirone,*,a Alessandra Garau,a Francesco Isaia,a Mark E. Light,bVito
Lippolis,a Riccardo Montis,a,b Mariano Andrea Scorciapinoa
5
Received (in XXX, XXX) Xth XXXXXXXXX 200X, Accepted Xth XXXXXXXXX 200X
First published on the web Xth XXXXXXXXX 200X
DOI: 10.1039/b000000x
Two new asymmetric ureidic receptors L1 (1-(1H-indol-7-yl)-3-
(quinolin-2-yl)urea) and L2 (1-(quinolin-2-yl)-3-(quinolin-8-
10 yl)urea) have been synthesised and their affinity towards
different anions tested in DMSO-d6. L1 adopts both in solution
and in the solid state an (E,Z) conformation. A moderate affinity
for acetate has been observed with L1 while no interaction has
been observed with L2. The different behaviour has been
15 ascribed to the presence/absence of the indole group. In the case
of L1 the indole group causes the formation of a peculiar
supramolecular architecture with two molecules of the receptor
binding the anions in (E,Z) conformation via H-bonds. L2 also
adopts an (E,Z) conformation in the solid state. However, the
20 absence of the indole in L2 hampers the formation of the
supramolecular assembly with the partecipation of anionic
species.
50 Scheme 1 Pictorial draw of the receptors studied in the paper (
= O)
•
= N;
•
Both were synthesised starting from 2ꢀisocyanatoquinoline
obtained by Curtius rearrangement from quinolineꢀcarbonyl
azide8 and 7ꢀaminoindole and 8ꢀaminoquinoline, respectively,
55 in dry toluene. In the case of L1 the resulting precipitate was
washed with DCM and then with MeOH to get the pure
product in 29% yield. In the case of L2 the pure product was
simply obtained by filtration from the reaction mixture as a
white solid in 63% yield (see ESI†). Crystals suitable for Xꢀ
60 ray diffraction analysis were obtained for both substituted
urea derivatives L1 and L2. L1 was crystallised by slow
evaporation from a 1:1 (v/v) mixture of DCM and MeOH
resulting in a solvate phase (L1α)9. A further crystallization
experiment from MeOH/THF 2:1 (v/v) in the presence of
65 tetrabutylammonium acetate, resulted in a new phase of the
receptor L1 (L1β)9. Crystals of L2 were grown by slow
evaporation from DMSO. A summary of the basic crystal data
are given in the ESI†.
A
popular area of supramolecular chemistry in which
hydrogen bonds play key role is anion recognition
a
25 performed by neutral receptors containing ureidic, amidic,
indolic etc. NH groups able to act as hydrogen bond donors
towards anionic substrates.1ꢀ4 Moreover, in biological
systems, the integrity of a huge number of biomolecular
structures, information storage and transfer processes,
30 replication and catalysis are strongly dependent on the
formation of specific patterns of complementary interꢀ and
intramolecular hydrogen bonds.5 For this reason designing,
developing and understanding new systems able to selfꢀ
assemble only by means of hydrogen bonds formation is one
35 of the challenges of modern supramolecular chemistry.6 When
designing an anion receptor many factors must be taken into
account such as the number and typology of the hydrogen
bond donor groups, the complementarity in shape and
dimension between the binding domain of the receptor and the
40 anionic substrate, and the nature of the receptors in terms of
formation of intraꢀ or interꢀmolecular hydrogen bonds (that
could prevent the availability of the donor groups for anion
coordination).
The two phases L1α (trigonal, Rꢀ3, Z’ = 1) and L1β
70 (orthorombic, Pna21, Z’ = 2) (Table S1), adopt an (E,Z)
conformation (Fig. 1a) with the formation of an
intramolecular hydrogen bond between one of the NHs of the
urea moiety and the nitrogen of the quinoline group (N(3)
⋅⋅⋅N(1) distances, are 2.658(4) Å for L1α and respectively
75 2.653(6) Å and 2.682(6) Å for L1β10) in agreement with the
literature data on solid state regarding pyridyl urea
derivatives.11ꢀ13 Moreover (Fig. 1a), the presence of the indole
group allows the formation of an additional intramolecular
hydrogen bond between the NH of the indole and the ureidic
80 carbonyl group (N4⋅⋅⋅O1 distances are 2.686(4) Å for L1α and
respectively 2.687(5) Å and 2.703(5) Å for L1β9).
Similarly to the two phases L1α and L1β, the crystal structure
of L2 (monoclinic, P21/c, Z’ = 2) shows an intramolecular
hydrogen bond (Fig. 1 c) involving one of the ureidic NH
85 group and the nitrogen of the quinoline group (N(4)⋅⋅⋅N(2) and
Following our interest in anion recognition involving indole
45 as hydrogen bond donor group7 we designed and succesfully
synthesised two new ureidic asymmetric derivatives: L1 which
contains a quinoline and an indole moieity, and L2 featuring
two quinoline moieties.
(N(6)⋅⋅⋅N(8) distances are respectively 2.697(2)
Å and
2.694(2) Å), resulting in an (E,Z) conformation (Fig. 1d).
90
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The SCs A are then differently assembled in the three
45 structures, generating major departures in the resulting crystal
packing (Figure 3). The analysis also reveals in the structure
of L1α the presence of 1ꢀD channels built by indolic units and
developing along the 001 direction. Furthermore the analysis
reveals that no hydrogen bond donor or acceptor site are
50 available in the cavity. These channels are consistent with the
fact that L1α crystallised including solvent molecules
(MeOH)17 in the crystal packing (see also ESI†).
Figure 1 Ureidic dimer and relevant intra and interꢀmolecular interactions
for L1α (a) as representative for the pair (L1α and L1β) and L2(b) in the
(E,Z) conformation. The numbering scheme is also reported. Centre of
inversion is indicated as • (symmetry code: ꢀx+5/3, ꢀy+1/3, ꢀzꢀ2/3).
5
A
further common feature in the three structures is
represented by the adoption of a similar supramolecular
synthon14 (Fig 1a and b) consisting of
Figure 3. Crystal packing representation of the three structures L1α, L1β
a
dimer 55 and L2. a) L1α viewed along the 001 direction; b) L1β viewed along the
010 direction; c) L2 viewed along the 100 direction. The molecules are
10 (centrosymmetric for L1α and pseudoꢀcentrosymmetric for
L1β and L2) connected via hydrogen bonds involving the
donor ureidic carbonyl group of one molecule and the ureidic
NH group not involved into intramolecular hydrogen bonds of
an adjacent molecule (N(2)⋅⋅⋅O(1) distances are 2.845(4) Å for
15 L1α, N(102)⋅⋅⋅O(201) and N(202)⋅⋅⋅O(101) distances are
colour coded according to the orientation of the ureidic CꢀO vector: blue
pointing towards the viewer, orange pointing away from the viewer. An
instance of the SC A viewed along its direction of propagation is also
60 indicated by black dashed lines.
We investigated whether the two receptors could assume in
solution the same conformation observed in the solid state and
which was their behaviour in the presence of anionic
substrates.
respectively 2.997(5)
Å and 2.848(5) Å
for L1β and
N(3)⋅⋅⋅O(2) and N(7)⋅⋅⋅O(1) distances are 2.830(2) and
2.888(2) Å for L2). This is not surprising if the similar
shape/conformation and the common set of hydrogen bond
20 donor and acceptor are taken into account.
65 In CDCl3 solution L1 adopts the same (E,Z) conformation
1
observed in the solid state as confirmed by HꢀNMR chemical
1
shift assigned by Hꢀ1H TOCSY experiments. In particular the
A crystal packing comparison of the three structures L1α,
L1β and L2, carried out using the XPac program15,16, reveals
that this common supramolecular synthon is precursor of a
higher dimensional common molecular arrangement
25 (experimental details of the analysis are provided in ESI†).
The analysis reveals a 1ꢀD similarity (dissimilarity index χ =
8.2)15b defined as Supramolecular Construct15a (SC A). This
consists of a row of ureidic dimers which respectively
propagates along the 001 direction for L1α (lattice vector =
30 7.098 Å), the 0-10 direction for L1β (lattice vector = 7.131 Å)
and the 100 direction for L2 (lattice vector = 8.041 Å). ).
Apart the NꢀH⋅⋅⋅O dimers discussed above (Figure 1), no
significant interactions are involved in connecting the SC A
(Figure 2) which is mainly the result of the close packing. The
35 only exception is represented by L1β, in which πꢀπ
interactions respectively involving the ureidic and quinolinic
moieties of adjacent dimers, contribute in connecting this
molecular arrangement (the shortest CenꢀCen distances are
respectively 3.63 Å and 3.80 Å).
H3A signal, involved in a strong intramolecular hydrogen
bond, is observed at 12.97 ppm, the H4A signal is observed at
70 10.20 ppm and the H2A one is observed at 7.86 ppm. The
chemical shift of the H2A signal is concentration dependent in
the concentration range of 20ꢀ0.25 mM (see Figure 4) in
agreeement with its involvement in an intermolecular
hydrogen bond forming a duplex as observed in the solid
75 state, while the H3A and the H4A signals are concentration
independent being locked by intramolecular hydrogen bonds.
1
A nonlinear regression analysis18 of the HꢀNMR data yielded
to a dimerization constant of 430± 37 Mꢀ1 (see ESI†).
40
Figure
2 Representation of the SC A along its direction of
propagation viewed along two perpendicular direction.
2
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Figure 4 1HꢀNMR stack plot of solutions of L1 in CDCl3 at 298 K at
decreasing concentrations. The arrows indicate the H2A signal moving
towards higher fields upon dilution.
Moreover, variable temperature 1HꢀNMR experiments
confirmed the presence of a duplex in solution in these
experimental conditions as, once again, the H2A signal moves
upfield by increasing the temperature (1.50⋅10ꢀ2 ppm Kꢀ1)
while the signal of H3A involved in an intramolecular
hydrogen bond shows a much lower shift with temperature
5
10 (5.27⋅10ꢀ2 ppm Kꢀ1); in the range 294ꢀ321 K;19 the H4A signal
resulted unaffected (see ESI†).
Anion binding studies were performed by means of HꢀNMR
1
titrations in CDCl3 in the presence of acetate, benzoate and
chloride (as their tetrabutylammonium salts). Interestingly,
15 upon addition of 0.4 equivalents of acetate or benzoate all the
NH signals broaden and the H8A signal starts to move
downfield. In particular, in the presence of an excess of
acetate (around 3 equivalents) the NH signals can be observed
again as sharp signals as shown in the stack plot in Figure 5.
1
Figure 6 HꢀNMR stack plot of a CDCl3 solution of L1 (0.005 M) upon
addition of tetrabutylammonium chloride (0.075 M) in CDCl3. The
40 arrows indicate the H8A (upfield) and the H2A (downfield) signals.
The broadening of the NH signals prevented us from
determining the affinity costants of L1 for the anionic
substrates. For this reason we moved to DMSOꢀd6, a solvent
more suitable for these type of studies.
45 In DMSOꢀd6, probably because of its higher solvating power,
the formation of the duplex was not observed as confirmed by
dilution and variable temperature experiments. However, on
the basis of the 1H chemical shift values observed
(10.12(H2A) , 10.89 (H4A) and 11.67 (H3A) ppm) in
50 comperison with those observed for the two ureidic and the
indolic NꢀH groups in the symmetric 1,3ꢀbis(1Hꢀindolꢀ7ꢀ
yl)urea,7c,20 (8.63 and 10.77 ppm, respectively) the presence
of the two aforementioned intramolecular Hꢀbonds, namely,
N3−H3A⋅⋅⋅N1 and N4−H4A⋅⋅⋅O1, can be inferred. This
55 conclusion is further supported by both twoꢀdimensional
NOESY21 and selective oneꢀdimensional DPFGSEꢀnoesy1d22
experiments (200 ms mixing time). On the basis of the
NOESY crossꢀpeaks relative intensity, an upper limit of 2.7 Å
has been applied to restrain the corresponding interꢀproton
60 distances together with the gromosꢀ53a6 force field23
parameters. One hundred structures were independently
calculated using a simulated annealing protocol24 with the
software Dynamo.25 Additional interꢀatomic distance
restraints were also introduced to simulate the two mentioned
65 intramolecular Hꢀbonds. Violations from the experimental
NOEs have never been observed. The 20 structure with the
lowest potential energy were then selected and used for the
analysis. Figure 7 shows the average structure together with
the quantitative estimation of the different NOE enhancements
70 (obtained analyzing the oneꢀdimensional noesy results with
the soꢀcalled PANIC method).26 It is interesting to note that
H2A and H4A protons resulted to have almost the same
distance from H3A, as reflected by comparable NOE
enhancements. However, H2A provided a relatively higher
75 NOEꢀenhancement to H8A, as well as H3A to H12A. In the
resulting molecular structure the two aromatic rings do not lie
on the same plane but are differently tilted with respect to the
carbonyl group, and H2A and H4A are located on opposite
sides of the molecule. Overall, the statistical analysis showed
80 that the most populated conformer is characterized by the two
20
1
Figure 5 HꢀNMR stack plot of a CDCl3 solution of L1 (0.005 M) upon
addition of tetrabutylammonium acetate (0.075 M) in CDCl3 at 298 K.
The arrows indicate the H8A signal.
In particular the signal for H3A is not affected by the presence
25 of the anionic substrate, indicating that this proton is still
involved in the intramolecular hydrogen bond N3−H3A⋅⋅⋅N1,
while the H2A, H4A, and H8A signals move downfield (about
1.5 ppm, 2.7 ppm, and 1.4 ppm, respectively). These results
suggest that upon addition of acetate the duplex is no longer
30 present in solution and the anion is bound to each monomer
by means of three hydrogen bonds, two from the NH moieties
(one ureidic and one indolic) and one from the CH group of
the quinoline.
A similar behaviour was observed in the presence of benzoate
35 while in the case of chloride the broaden of the NH signals
was less dramatic (Figure 6).
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dihedral angles N1−N2−C10−O1 and N4−N3−C10−O1 equal
to ꢀ106° and +15°, respectively. The (E,Z) conformation of the
free receptor is thus maintened in solution both in CDCl3 and
in DMSOꢀd6.
intramolecular hydrogen bond with N1. As observed in CDCl3,
also in DMSOꢀd6 the C8−H8A is also affected by the presence of
anions.
13.40
12.40
5
11.40
C8-H8
N2-H2
10.40
N4-H4
N3-H3
9.40
8.40
7.40
0.00
1.00
2.00
3.00
4.00
5.00
6.00
AcO- equiv.
40
Figure
8
1HꢀNMR titration curves of L1 (0.005 M) with
tetrabutylammonium acetate (0.075 M) in DMSOꢀd6.
Similar titration curves were obtained with the other anions
(see ESI†).
Figure 7 The most populated conformation adopted in solution by L1
calculated on the basis of the experimental NOEs in DMSOꢀd6 is reported
together with the quantitative estimation of the NOE enhancements. The
45 As we observed the most interesting results with acetate we
decided to perform a detailed NMR study of L1 in the
presence of this anion in order to understand the
conformational changes experienced by the receptor and the
nature of the complex.
10 protons not mentioned in the discussion are omitted for clarity.
1
Anionꢀbinding studies were performed by means of HꢀNMR
titrations in DMSOꢀd6. In this experimental conditions no
broadening of the NH signals was observed, as expected. The
EQNMR program27 was used to calculate stability constants
50 Following the same procedure adopted in the absence of the
anion, the most populated conformer for L1 in the presence of
one equivalent of acetate was computed on the basis of the
1HꢀNMR noesy experiments. It is interesting to note that the
2DꢀNOESY crossꢀpeaks pattern resulted to be comparable to
55 that obtained in the absence of acetate, indicating that the
conformational changes induced by the anion are not
dramatic. Violations of the experimental NOEs have never
been observed in all of these three cases and the
N3−H3A⋅⋅⋅N1 intramolecular Hꢀbond was always present. In
60 particular, three different possible complexes have been
hypothesised, all of which are, at least in principle,
compatible with the 1:1 binding model derived from the
titration curves (Figure 10). First, one acetate molecule might
coordinate to the H2A, the H4A and the H8A hydrogens of
65 the same L1 molecule (Figure 9a). Second, two acetate
molecules could coordinate to two L1s, thus forming a duplex,
by bridging analogous NꢀH groups, i.e. one of the acetates
coordinating both the H2As and the H8As, while the other
both the H4As (Figure 9b). Lastly, the duplex could be
70 formed by two acetate molecules coordinating different NꢀH
groups from two L1s (Figure 9c).
1
15 from the HꢀNMR titration curves obtained (see ESI†) fitting
the data to a 1:1 binding model. As shown in Table 2
moderately high stability constants were observed for the
adducts formation between L1 and the anions considered with
the highest value of Ka = 1203 Mꢀ1 for acetate. However, the
20 affinity of L1 towards anions is lower than that observed with
symmetric bisꢀindolylureas7c and symmetric and asymmetric
carbazolylureas.7b
This is probably due to the fact that only two of the three NHs
available in L1 are effectively interacting with the anionic
1
25 substrate. During HꢀNMR titrations, in fact, we noticed that
of the three NH groups of L1 only two (namely the H2 and the
H4A) were shifted downfield upon addition of anions as
shown in Figure 8 in the case of acetate.
30 Table 1. Equilibrium constants (Ka/Mꢀ1) for the reactions of L1 and L2
ꢀ
with the tetrabutylammonium anion salts considered (HCO3 was used as
tetraethylammonium salt) in DMSOꢀd6 at 300 K. All errors estimated to
be ≤10% (except for chloride for which the error is estimated to be 21%)
(see ESI †).
Anion
Fꢀ
L1
deprot.
12
1203
634
L2
deprot.
no interaction
no interaction
no interaction
no interaction
no interaction
Clꢀ
CH3COOꢀ
C6H5COOꢀ
ꢀ
HCO3
282
n.d
ꢀ
H2PO4
35 The N3−H3A resulted unaffected by the addition of all the
anions considered, indicating its involvement in the
4
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H4A and H8A protons changed, as said, but the H5A, H7A
35 resonances also sligthly shifted, while all the other signals
remained unaffected. First, this is clearly not compatible with
the model of one acetate molecule coordinating a unique L1.
The formation of a supramolecular assembly like those in
Fig.10b and Fig.10c, on the other hand, provides a valid
40 explanation. Infact, while the shifts for H2A, H4A and H8A
can be explained considering the coordination of the anion,
only the approaching of a second molecule of L1 involved in
the supramolecular assembly, might affect the chemical shift
of the H5A and H7A protons. The radial distribution functions
45 were computed for all of the aromatic ring hydrogens of one
L1 molecule with respect to all the carbons of the other (see
ESI†). Definitely, among the two assemblies tentatively
simulated, only the second one (see Fig. 9c) resulted to have
the H5A and H7A protons as the closest atoms to the second
50 L1 molecule. For the sake of clarity, Figure 11 shows the most
Figure 9 Proposed coordination modes of L1 with acetate.
Correspondingly, the most populated conformer obtained in
each of the cases showed the same values for the
N1−N2−C10−O1 and N4−N3−C10−O1 dihedral angles, ca. ꢀ
136° and ꢀ67°, respectively. Thus, compared to the conformer
obtained in the absence of anion (see Fig. 5), while the tilt
angle of the quinoline moiety remains almost comparable (due
5
representative
calculated
configuration
for
this
supramolecular assembly.
10 to the presence of the aforementioned intramolecular
H−bond), that of the indole changes dramatically. Figure 10
shows the average structure of L1 in the presence of one
equivalent of acetate together with the quantitative estimation
of the different NOE enhancements.
Figure 11 The most representative calculated configuration for two L1
55 and two interacting acetate molecules in the assembly formed in DMSOꢀ
d6.
15
The proposed binding mode has never been observed, to the
best of our knowledge, in indole containing ureas, both
symmetric and asymmetric, with anions.
Figure 10 The most populated conformation adopted in solution by L1 in
the presence of acetate calculated on the basis of the experimental NOEs
in DMSOꢀd6 is reported together with the quantitative estimation of the
7, 28
NOE enhancements. The protons not mentioned in the discussion are 60 As shown in Table 1 fluoride causes deprotonation of the
20 omitted for clarity.
receptor with a colour change in the solution from colourless
to yellow and a change in the fluorescence emission with the
formation of a new luminescence band in the visible region
Similarly to what was observed in the absence of the acetate,
(see Fig. 12). The addition of dihydrogenphosphate causes the
H2A and H4A have almost the same distance from H3A. 65 loss of the signal of the H2A in the 1HꢀNMR titration: this
However, in the presence of acetate, the inter−HN NOE
25 enhancements are higher than the H2A−H8A and the
H3A−H12A ones. These observations further confirmed the
structural change induced by the presence of the acetate,
which, as shown in Figure 10, resulted in all the three HNs
being located on the same side of the molecule. Finally, a
could be ascribed to a deprotonation or to a strong binding.
However, the interaction with this anion is not accompained
by a change of the photophysical properties of the system.
1
30 deeper analysis of the H chemical shift values obtained in the
absence and in the presence of the acetate, allowed for
discriminating between the three proposed binding
possibilities. Indeed, not only the chemical shift of the H2A,
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700
600
500
400
300
200
100
0
Acknowledgements
50
We would like to thank MIUR (Ministero dell’Istruzione.
dell’Università e della Ricerca Scientifica) for financial
support (Project PRIN 2009 – 2009Z9ASCA).
Notes and references
*Corresponding authors: Fax: +(39) 0706754456, Tel: +(39)
55 0706754452, E-mail: ccaltagirone@unica.it (C.C.).
a Universita’ degli Studi di Cagliari, Dipartimento di Scienze Chimiche e
Geologiche, S.S. 554 Bivio per Sestu, Monserrato (CA), 09042, Italy.
b School of Chemistry, University of Southampton, Southampton, SO17
1BJ, UK. Fax: +44 23 8059 6805; Tel: +44 23 8059 6805; E-mail:
60 M.E.Light@soton.ac.uk
†Electronic Supplementary Information (ESI) available: additional
information as noted in the text including synthetic details for the
preparation of L1 and L2, and X-ray crystallographic files in CIF format
[CCDC n. ]. See DOI: 10.1039/b000000x/
330
380
430
480
530
580
wavelength (nm)
Figure 12 Changes in the fluorescence spectra of L1 (1.27⋅10ꢀ5 M) upon
addition of increasing amounts of TBAF (2.5⋅ 0ꢀ2 M) in DMSO. Inset:
Colour change of L1 (0.005 M) upon addition of five anion equivs. (0.075
ꢀ
5
M) in DMSO. From left to right: L1, Fꢀ, AcOꢀ, Clꢀ, BzOꢀ, HCO3 and
ꢀ
H2PO4 .
Experimental evidence suggests that L2 adopts
a (E,Z)
65
conformation in solution, too. Infact, we observed negligible
changes (see ESI) in the HꢀNMR spectrum of L2 in DMSOꢀd6
1
1
2
J. L. Sessler, P.A Gale and W.S. Cho, Anion Receptor Chemistry,
2006, The Royal Society of Chemistry, Cambridge, UK;
10 upon addition of anions (except for fluoride that causes
deprotonation without any change, however, in the absorption
or emission properties of the system). Interestingly, the signal
of one of the two ureidic NHs of the free L2 is far downfield
(13.93 ppm) compared to the analogous L1 that falls at 11.64
15 ppm, and to the analogous symmetric bisꢀindolylurea that falls
at 8.63 ppm7c suggesting that this NH is involved into an even
stronger intramolecular hydrogen bond in solution compared
to that observed for L1; moreover, its chemical shift is
concentration independent as observed in the compound N,N′ꢀ
20 2,diꢀpyridilurea (for this compound the urea NH signal falls at
12.80 ppm in CDCl3; we could not perform a 1HꢀNMR
experiment on L2 in CDCl3 due to the very low solubility of
the molecule in this solvent).29 All this is consistent with L2
assuming an (E,Z) conformation in solution with one ureidic
25 NH being strongly intramolecularly hydrogen bonded as
observed for L1. However, in this case, the absence of the
indole group as hydrogen bond donor does not allow the
interaction with anions as there would be only one hydrogen
able to bind the guests via hydrogen bond. (Table 2).
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30 In conclusion we have shown that when designing an anion
receptor it is fundamental to consider the possibility of intraꢀ
molecular hydrogen bonds formation.
8
H. Saikachi, T. Kitagawa, A. Nasu, H. Sasaki, Chem. Pharm. Bull.,
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9 Note that the notation α and β is based on order of discovery and does
not refer to any stability order, nor any melting temperature order. L1
α is solvate, the exact nature is unlcear, but an assumed 3 MeOH
molecules were treated using squeeze.
The indole moiety has demonstrated to be very useful for
anion binding for the presence of the NH group that can act as
35 an efficient hydrogen bond donor towards anionic substrates.
In the case of L1, where an indole group has been replaced by
a quinoline, the presence of an AD couple strongly stabilises
the anti (E,Z) conformation even in the presence of anions.
This favours the formation of a supramolecular architecture in
40 solution in which two molecules of L1 cooperate to bind
anions in an unusual fashion compared to that observed in
similar symmetric and asymmetric indoleꢀcontaining ureas. In
contrast, L2 in which the indole moieties were replaced by
quinolines, no interaction with anions is observed, thus
45 confirming the crucial role played by indoles in designing
neutral receptors for anion recognition.
10 The two values respectively refer to the two independent molecule in
the asymmetric unit
95 11 C.ꢀH. Chien, M.ꢀKit Leung, J.ꢀK. Su, G.ꢀH. Li, YiꢀH. Liu and Yu
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14 G. R. Desiraju, Angew. Chem. Int. Ed. , 1995, 34, 2311.
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17 From consideration of the synthesis and crystallisation conditions the
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