Halogen-substituted ureas for anion binding: solid state and solution studies

Article abstract of DOI:10.1080/10610278.2017.1377343

Herein, we report the synthesis and the anion binding properties of a family of N,N′-diphenylureas L₁-L₁₅, bearing on the aromatic ring(s) halogens (chlorine and iodine) and/or nitro or trifluoromethyl electron-withdrawing groups. The analysis of the crystal structures obtained from single crystal X-ray diffraction experiments shows that self-assembled chains or tapes connected via N–H···O hydrogen bonds are the most commonly adopted arrangements for this type of molecules in the crystal lattice. In the presence of anion guests or solvent molecules with competing hydrogen bond donors and acceptors, other supramolecular arrangements can be observed. Solution studies conducted in DMSO-d₆/0.5% H₂O by means of ¹H-NMR titrations show the formation of 1:1 adducts with all receptors. The different observed affinities of the receptors for the anion guests were rationalised in terms of steric hindrance of the substituents on the phenyl rings and their electron-withdrawing properties.

Full text of DOI:10.1080/10610278.2017.1377343

Supramolecular Chemistry
ISSN: 1061-0278 (Print) 1029-0478 (Online) Journal homepage: http://www.tandfonline.com/loi/gsch20
Halogen-substituted ureas for anion binding: solid
state and solution studies
Arianna Casula, Marco Fornasier, Riccardo Montis, Alexandre Bettoschi,
Stephen P. Argent, Alexander J. Blake, Vito Lippolis, Laura Marongiu,
Giacomo Picci, Jeremiah P. Tidey & Claudia Caltagirone
To cite this article: Arianna Casula, Marco Fornasier, Riccardo Montis, Alexandre Bettoschi,
Stephen P. Argent, Alexander J. Blake, Vito Lippolis, Laura Marongiu, Giacomo Picci, Jeremiah P.
Tidey & Claudia Caltagirone (2017): Halogen-substituted ureas for anion binding: solid state and
solution studies, Supramolecular Chemistry, DOI: 10.1080/10610278.2017.1377343
To link to this article: http://dx.doi.org/10.1080/10610278.2017.1377343
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Date: 25 September 2017, At: 22:38

Supramolecular chemiStry, 2017
https://doi.org/10.1080/10610278.2017.1377343
Halogen-substituted ureas for anion binding: solid state and solution studies
Arianna Casulaa, Marco Fornasiera, Riccardo Montisa,b, Alexandre Bettoschia, Stephen P. Argentc,
Alexander J. Blakec, Vito Lippolisa, Laura Marongiua, Giacomo Piccia, Jeremiah P. Tideyc and Claudia Caltagironea
aDipartimento di Scienze chimiche e Geologiche, università degli Studi di cagliari, monserrato, italy; bDepartment of materials, imperial college
london, london, uK; cSchool of chemistry, university of Nottingham, Nottingham, uK
ABSTRACT
ARTICLE HISTORY
received 20 July 2017
accepted 2 September 2017
Herein, we report the synthesis and the anion binding properties of a family of N,N′-diphenylureas
L1-L15, bearing on the aromatic ring(s) halogens (chlorine and iodine) and/or nitro or trifluoromethyl
electron-withdrawing groups. The analysis of the crystal structures obtained from single crystal X-ray
diffraction experiments shows that self-assembled chains or tapes connected via N–H···O hydrogen
bonds are the most commonly adopted arrangements for this type of molecules in the crystal lattice.
In the presence of anion guests or solvent molecules with competing hydrogen bond donors and
acceptors, other supramolecular arrangements can be observed. Solution studies conducted in DMSO-
d6/0.5% H2O by means of 1H-NMR titrations show the formation of 1:1 adducts with all receptors. The
different observed affinities of the receptors for the anion guests were rationalised in terms of steric
hindrance of the substituents on the phenyl rings and their electron-withdrawing properties.
KEYWORDS
anion binding; phenylurea
CONTACT riccardo montis
r.montis@imperial.ac.uk; claudia caltagirone
ccaltagirone@unica.it
the supplemental data for this article is available online at https://doi.org/10.1080/10610278.2017.1377343
© 2017 informa uK limited, trading as taylor & Francis Group

2
A. CASULA ET AL.
scaffold, it is possible to modulate the strength of the inter-
action between the receptor and anion. By geometric
analysis of the hydrogen bonding interactions they also
suggested that, moving from meta to para to 3,5-dinitro
substitution, increases the hydrogen bond strength.
In recent years, beside hydrogen bond-, halogen bond-
based receptors have been developed for anion binding.
The term ‘halogen bonding (XB)’ was officially defined by
IUPAC in 2013 as a non-covalent interaction between a
halogen bond donor R–X (where X is a halogen atom with
an electrophilic region and a R is any organic group) and a
halogen bond acceptorY (whereY is a nucleophilic molec-
ular entity) (9). Halogen bonds RX···Y are almost linear and
they have an energy comparable with hydrogen bonds
(5–180 kJ mol−1).
Introduction
The development of synthetic receptors for anion bind-
ing, sensing, catalysis and transport is one of the most
active area of Supramolecular Chemistry (1). In particular,
the design and synthesis of neutral receptors capable of
recognising anions in competitive solvent mixture, and
possibly in water, is rather challenging because of com-
petition issues. Urea and thiourea-based receptors have
been widely studied for anion binding because of their
synthetic accessibility and also their ability to interact
through strong, directional hydrogen bonds (2). Recently,
selenoureas have also been proposed for anion binding
and sensing (3). The urea (or thiourea) moiety bearing two
N–H groups can bind the anionic guest (in particular spher-
ical anions such as halides) as a monodentate ligand with a
single acceptor atom to yield a six-membered chelate ring.
They may also bind as a bidentate ligand with two adjacent
oxygen atoms in an oxyanion to form an eight-membered
chelate ring. Among the different type of urea derivatives
developed over recent years, N,N′-diphenylurea represents
one of the simplest and most popular receptor for anion
binding (4).
In the solid state, this class of compounds have been
extensively investigated (5). N,N′-diphenylurea forms
robust and predictable self-assembled chains or tapes
connected via N–H···O hydrogen bonds. Etter et al. demon-
strated that the presence of electron-withdrawing groups
in diaryl urea decreases the tendency to form self-assem-
bled 1-D chains (6). This is due to the increased acidity of
the ortho aromatic C–H that forms intramolecular hydro-
gen bonds with the urea C=O, reducing its ability to inter-
act with adjacent urea NHs. Therefore, the disruption of
these 1-D chains is often associated with a coplanar confor-
mation of the phenyl rings with respect to the urea plane.
A similar behaviour was described by Nangia and col-
laborators who investigated a family of substituted N-X-
phenyl-N′-p-nitrophenyl urea compounds (X=H, F, Cl, Br, I,
CN, C≡CH, CONH2, COCH3, OH, Me) (7). The results allowed
the authors to classify the family of structures into two
main categories: (i) urea tape structures, formed by clas-
sic urea N–H···O hydrogen bonds, in which phenyl rings
adopt a twisted conformation with respect to the urea
plane, and (ii) non-urea tape structures in which the phe-
nyl groups adopt a coplanar conformation and the classical
urea N–H···O hydrogen bonds are replaced by interactions
with NO2 groups or solvent molecules.
Taylor et al. have reported a family of urea based recep-
tors for anion recognition that contain iodoperfluoro-arene
groups (10). These systems are able to interact with anions
via both hydrogen and halogen bonds.
An example of simple symmetric N,N′-diphenylurea
receptors para substituted with halogens and able to bind
anions forming both hydrogen and halogen bonds in solu-
tion and in the solid state was reported by Das et al. (11).
Inspired by these results we decided to synthesise a
new family of simple asymmetric N,N′-diphenylurea recep-
tors L1-L15 for anion recognition. These receptors are sub-
stituted on one phenyl ring with iodine and chlorine in
various positions (ortho and para for chlorine and ortho
for iodine), and with a nitro or a trifluoromethyl moiety
on the other (Figure 1).
These different combinations of substituents on the two
phenyl groups were chosen in order to evaluate the effect
of electron-withdrawing groups and halogens on anion
binding ability. Receptors L1, L4, L7, L10, and L13, whose syn-
thesis was already reported in the literature (6b, 12), were
used as control molecules for each series of receptors with
the same substituents. We tested receptors L1-L15 with a
set of anions of different geometries [Y-shape (AcO− and
−
BzO−), spherical (Cl− and F−) and tetrahedral (H2PO4 )] by
means of 1H-NMR spectroscopy and, where possible, single
crystal X-ray diffraction.
Results and discussion
Synthesis
Receptors L1-L15 were designed and successfully synthe-
sised according to Schemes 1–3.The syntheses are based on
the simple nucleophilic addition of an isocyanate (phenyl
isocyanate, nitro-phenyl isocyanate or trifluoromethyl-phe-
nyl isocyanate for receptors L1-L3, L4-L12 and L13-L15 respec-
tively) and the appropriate aniline. As mentioned in the
introduction, the synthesis of receptors L1, L4, L7, L10, and
Recently, Gale, Coles, et al. described a systematic struc-
tural analysis on a series of urea-based anion receptor
complexes including high-resolution, experimental and
electron density study (8). The authors demonstrated that
by systematically altering the position and the number of
electron-withdrawing nitro groups in the 1,3-diphenylurea

SUPRAMOLECULAR CHEMISTRY
3
Figure 1. receptors L1-L15
.
Scheme 1. reaction scheme adopted for the synthesis of L1, L2, and L3.
L13, had been reported before (6b, 12). After two hours of
reflux in DCM, all the products were obtained as pure solids
by precipitation, in widly variable yields depending on the
substituents added to the systems (20–96%).
from various solvents and in the presence of different anion
guests. Surprisingly, we could isolate crystals suitable for
single crystal X-ray diffraction only for the adduct L6-
tetrabutylammonium benzoate (L6-BzO−). Crystallisations
of free receptors L1-L15 produced single crystals only for L1,
L5, L8, L14, and L15. In the case of receptor L2, crystallisations
in presence of tetrabutylammonium fluoride or tetrabu-
tylammonium iodide produced two distinct polymorphic
phases, designated L2α and L2β, respectively. L8 and L11
Single crystal X-ray diffraction
To investigate binding properties in the solid state of L1-
L15, all the receptors were crystallised by slow evaporation

4
A. CASULA ET AL.
Scheme 2. reaction scheme adopted for the synthesis of L4-L12.
Scheme 3. reaction scheme adopted for the synthesis of L13, L14, and L15.
crystallised as solvate forms, a DMSO solvate L8•DMSO and
a mixed solvate L11•2DMSO•DMF, respectively.
According to previous observations, the planar conforma-
tion of the two solvate forms is stabilised by intra-molecu-
lar C–H⋅⋅⋅O hydrogen bonds involving the urea C=O group
and aromatic CHs of the phenyl groups (H⋅⋅⋅O distances lie
in the range 2.20–2.28 Å, C⋅⋅⋅O distances lie in the range
2.836(3)–2.876(3) Å). However, weak intra-molecular C–
H⋅⋅⋅O hydrogen bonds are also observed in most of the
structures which adopt a tilted conformation. Excluding
L15 and the two polymorphs L2α and L2β, which show
intra-molecular interactions only on the substituted ring,
the structures (see Table S3, Supporting Information) of
the free receptors show a set of intramolecular C–H⋅⋅⋅O
interactions with H⋅⋅⋅O distances in the range 2.30–2.58 Å
(C⋅⋅⋅O distances in the range 2.828(2)–2.958(8) Å). In the
case of L5 this intramolecular interaction is also assisted
by a further intramolecular N–H⋅⋅⋅O hydrogen bond involv-
ing one of the urea NHs and the nitro group in position
A summary of unit cell parameters and main crystallo-
graphic data for the set of crystal structures collected is
shown in Table 1. Details of crystallisation experiments,
intermolecular interactions and crystal packing descrip-
tions are reported in Supporting Information.
Considering the urea molecular unit, comparison of
the molecular conformation for the ten crystal structures
shows that in all the structures, urea NH groups are ori-
ented trans with respect to the carbonyl group, confirming
the behaviour generally observed in crystal structures of
urea derivatives. Furthermore, in most of them, both phe-
nyl rings are slightly tilted with respect the plane of the
urea function (Table 2). The only exception is represented
by the two solvated forms, L8•DMSO and L11•2DMSO•DMF,
in which the phenyl rings are co-planar with the urea plane.

SUPRAMOLECULAR CHEMISTRY
5
Table 1. unit cell parameters for the crystal structures of L1, L2α, L2β, L5, L8, L14, L15, L8•DmSo, L11•2DmSo•DmF, and L6-BzO−.
L1
L2α
L2β
L5
L8
CCDC 1561823
CCDC1561826
CCDC1562645
CCDC1561828
CCDC1561825
Formula
FW
crystal System
Space Group
c13h12N2o
212.25
orthorhombic
Pna21
c13h10N2ocl2
281.13
triclinic
P-1
c13h10N2ocl2
281.13
triclinic
c13h9N3o3cl2
326.13
monoclinic
P21/n
c13h9N3o3cl2
326.13
orthorhombic
Pna21
P-1
a/Ǻ
b/Ǻ
c/Ǻ
α/º
β/º
γ/º
9.0641(3)
10.3509(3)
11.7422(3)
90
4.6123(14)
11.9420(5
22.8508(7)
93.005(3)
92.645(3)
97.764(3)
1243.57(8)
293(2)
4.5612(3)
11.5202(11)
12.1448(9)
103.972(7)
94.249(5)
95.458(6)
613.35(8)
120(2)
4.6027(7)
48.5814(8)
5.9207(14)
90
95.7193(17)
90
42.4563(6)
6.5738(1)
4.7887(1)
90
90
90
90
90
V/Ǻ3
T/K
Z
1101.68(5)
120(2)
1317.32(4)
120(2)
1336.52(4)
120(2)
4
4
2
4
4
L14
L15
L8•DmSo
L
11•2DmSo•DmF
L6-Bzo−
ccDc 1562644
ccDc 1561819
ccDc 1561821
ccDc 1561822
ccDc1561827
Formula
FW
crystal system
Space group
c14h9N2oF3cl2
349.13
monoclinic
Cc
c14h10N2oF3i
406.14
orthorhombic
Pca21
c30h30cl4N6o8S2
808.52
c15.68h15.67cl2N3.68o4S0.31
c36h51iN4o5
746.70
monoclinic
P21/n
400.66
monoclinic
P21/n
triclinic
P-1
a/Ǻ
b/Ǻ
c/Ǻ
α/º
β/º
γ/º
11.4548(2)
13.5410(2)
9.0285(2)
90
92.4156(16)
90
29.971(5)
4.5599(7)
10.4038(14)
90
90
90
1421.8(4)
120(2)
12.0136(4)
12.6801(4)
13.8642(5)
65.778(3)
72.336(3)
66.334(3)
1739.57(12)
120(2)
21.6216(9)
3.8114(1)
22.9689(10)
90
115.885(5)
90
8.8751(2)
22.2235(3)
18.3822(3)
90
92.239(2)
90
V/Ǻ3
T/K
Z
1399.16(4)
120(2)
1702.94
120(2)
3622.9(1)
120(2)
4
4
2
4
4
involving the urea group. Only L6-BzO−, L8•DMSO and
L11•2DMSO•DMF adopt alternative supramolecular syn-
thons. In these structures, the presence of the guest mol-
ecule with a set of competing hydrogen bond acceptors
prevents the formation of the typical urea-urea N–H⋅⋅⋅O
tapes. Accordingly, we discuss separately the three struc-
tures L8•DMSO, L11•2DMSO•DMF and L6-BzO− and start
our discussion focusing on the supramolecular features
of free receptors.
Table 2. torsion angles τ1 and τ2.
*
*
τ1
τ2
τ1′
–
τ2′
–
L1
−42.8(3)
−49.1(8)
−43.1(5)
−41.2(3)
−2.1(4)
−28.3(3)
−3.9(4)
−22.6(8)
−43(3)
−41.9(4)
38.1(3)
43.5(8)
56.1(5)
35.6(3)
0.5(4)
23.1(3)
7.5(4)
27.4(7)
44(3)
38.5(4)
L2α
L2β
L5
−52.9(8)
−54.4(7)
–
–
–
–
–
–
L
11•2DmSo•DmF
L8
One-dimensional N–H⋅⋅⋅O chains
L8•DmSo
L14
−3.5(4)
9.7(4)
Structures of the free receptors show 1-D urea chains, in
most cases connected by the robust bifurcated N–H⋅⋅⋅O
supramolecular synthon (H⋅⋅⋅O distances are in the range
1.95–2.70 Å, N⋅⋅⋅O distances are in the range 2.775(2)–
3.406(6) Å). The shape of the 1-D chains is very similar in
all the structures, consisting of linear arrangements of
molecules. The only exceptions are L1 and L14 in which
the chains adopt a zig-zag motif (Figure 2(a) and (f)). In
the case of L1 the phenyl groups within the urea molecule
are oriented approximately perpendicular to each other
with aromatic hydrogens pointing toward the centre of the
phenyl rings of adjacent urea units and forming T-shaped
edge-to-face interactions (8b) (C–H⋅⋅⋅Centroid distances
2.99 Å). In the case of L14, adjacent receptor molecules are
slightly tilted along the direction of propagation of the
–
–
–
–
–
–
L15
L6-BzO−
*For crystal structures with Z′ = 2 we use τ1′ and τ2′ to indicate torsional angles
for the second symmetrically independent molecule.
ortho (H⋅⋅⋅O distance is 2.24) Å, N⋅⋅⋅O distance is 2.935(4)
Å). Interestingly, L6-BzO−, adopts a conformation with the
phenyl rings tilted out with respect the urea plane, show-
ing only one C–H⋅⋅⋅O intramolecular interaction involving
the CH in the ortho position on the iodo-substituted ring
and the C=O of the urea group (H⋅⋅⋅O distance is 2.47 Å,
C⋅⋅⋅O distance is 2.920(4) Å).
Most of the structures show the classical 1-D chains
connected by three-centre N–H⋅⋅⋅O hydrogen bonds

6
A. CASULA ET AL.
Figure 2. (colour online) Ball and stick images of the one-dimensional urea chains for structures of free receptors: (a) L1; (b) L2α; (c)
L2β; (d) L5; (e) L8; (f) L14 and (g) L15. For structure L2α only one independent molecule is reported as representative of the shape of one-
dimensional urea chains. N–h⋅⋅⋅o hydrogen bonds are indicated using black dashed lines; atoms of iodine in purple, chlorine in dark
green, fluorine in green/yellow, nitrogen in blue, oxygen in red, hydrogen in white and the carbon scaffold in grey. other interactions
have been removed for clarity.
1-D chain. As a consequence, the N–H⋅⋅⋅O hydrogen bond
involves only one of the urea NH moieties (Figure 2(f)). A
similar interaction is observed in L8 (Figure 2(e)) but in this
case the 1-D urea chain adopts a linear shape.
Contrary to previous studies (7), while the substitution
at the phenyl rings introduces potential competing groups
with respect to hydrogen bonding, no such competition is
observed in the free receptors reported herein. However, in
the case of L8, the urea NHs are also involved in the forma-
tion of a further N–H⋅⋅⋅O interaction (Figure 3(a)) with the
NO2 groups in position meta of adjacent 1-D chains (H⋅⋅⋅O
distance are 2.42 and 2.44 Å, N⋅⋅⋅O distance are 3.142(2)

SUPRAMOLECULAR CHEMISTRY
7
and 3.145(2) Å). This particular supramolecular synthon
is not observed in the case of the substituted o-NO2
receptor, L5, which instead forms centro-symmetric dimers
with aromatic hydrogens of an adjacent urea unit via
C–H⋅⋅⋅O interactions (Figure 3(b)). In the case of L15, the
urea C=O group is involved in a second interaction (Figure
3(c)) with the iodo substituents of adjacent chains [I⋅⋅⋅O
distance is 3.50(2) Å]. No such behaviour was observed in
the crystal structure published by Koshti et al. (5e), which
corresponds to our receptor L3, where the iodo- substit-
uents only interact via weak C–H⋅⋅⋅I and I⋅⋅⋅I interactions
with neighbouring molecules.
The effect of varying the substituent groups, particu-
larly the set of electron-withdrawing groups chosen for
the design of receptors L1-L15, seems to have no consist-
ent effect on the strength of the N–H⋅⋅⋅O hydrogen bonds.
Bond length analysis of the N–H⋅⋅⋅O intermolecular and
weaker C–H⋅⋅⋅O intramolecular interaction (see Table S3
in Supporting Information) reveals that for structures L1,
L2α, L2β, L5 and L15 these are very similar, with N–H⋅⋅⋅O
and C–H⋅⋅⋅O distances in the range 1.95–2.24 Å and 2.44–
2.58 Å, respectively (N⋅⋅⋅O distances in the range 2.775(2)–
2.935(4) Å; C⋅⋅⋅O distances in the range 2.881(3)–2.958(8) Å).
In the case of L8 and L14, when compared to L1, the pres-
ence of electron-withdrawing groups at the phenyl rings
slightly increases the strength of the intra-molecular C–
H⋅⋅⋅O interactions, with H⋅⋅⋅O distances decrease from the
range 2.44–2.53 Å for L1 to 2.30–2.40 Å for L8 and L14 (range
of C⋅⋅⋅O distances decreasing from 2.881(3)–2.973(3) Å for
L1 to 2.828(2)–2.920(7) Å for L8 and L14).
approximately coplanar with the urea plane forming short
intramolecular C–H⋅⋅⋅O interactions. This is a result of the
increased acidity of the aromatic hydrogens due to the
presence of the electron-withdrawing groups. Previous
studies (5c, 5d, 6), have proposed that, in such a case, the
urea C=O is made a weaker hydrogen bond acceptor and
the urea NH groups preferentially interact with solvent
molecules instead, thus disrupting the 1-D urea-urea
assemblies.
Structure L8•DMSO crystallises with two independ-
ent receptors in the asymmetric unit. These interact with
each other via C–H⋅⋅⋅Cl and C–H⋅⋅⋅O interactions (H⋅⋅⋅Cl
distances are 2.79 and 2.92 Å, C⋅⋅⋅Cl distances are 3.696(2)
and 3.854(2) Å; H⋅⋅⋅O distances are 2.46 and 2.50 Å, C⋅⋅⋅O
distances are 3.244(3) and 3.317(3) Å) involving Cl and NO2
groups in phenyl rings and the aromatic hydrogen in the
para position to form a 1-D chain (Figure 4). Each independ-
ent receptor interacts with a molecule of DMSO via N–H⋅⋅⋅O
hydrogen bonds involving urea NHs (H⋅⋅⋅O distances are
in the range 1.87–2.25 Å, N⋅⋅⋅O distances are in the range
2.737(3)–3.037(3) Å). Solvent molecules also interact with
urea C=O groups via weak C–H⋅⋅⋅O interactions involving
methyl groups of DMSO (H⋅⋅⋅O distances are 2.41 and
2.43 Å, C⋅⋅⋅O distances are 3.203(3) and 3.383(3) Å). A more
detailed description of the crystal packing is reported in
Supporting Information.
Structure L11•2DMSO•DMF formed a DMSO/DMF sol-
vate with the two solvents disordered to share the same
molecular site in a 2:1 ratio, respectively. In this structure,
the receptor forms centro-symmetric dimers via C–H⋅⋅⋅O
interactions (H⋅⋅⋅O distance is 2.51 Å, C⋅⋅⋅O distance is
3.337(3) Å) involving the urea C=O group and the aromatic
hydrogen in a position meta to the di-chloro substituted
phenyl ring (Figure 5). This dimer exposes the urea NH
groups which interact with neighbouring solvent mole-
cules via N–H⋅⋅⋅O hydrogen bonds involving the S=O or
C=O groups, depending on the solvent present. The H⋅⋅⋅O
distances are in the range 1.95–2.48 Å (N⋅⋅⋅O distances
are in the range 2.801(5)–3.226(12) Å). Receptor mole-
cules interact along the shortest axis of the unit cell via
π⋅⋅⋅π stacking (centroid–centroid distance 3.811(1) Å). A
Solvates and receptor-anion structures
Crystallisation of receptors L6, L8 and L11 in the presence of
guest molecules such as solvents or anions produced two
solvate forms, L8•DMSO and L11•2DMSO•DMF, correspond-
ing to a DMSO and a DMSO/DMF solvate, respectively
and one benzoate complex of the receptor L6, labelled as
L6-BzO−.
As mentioned above, in the solvate compounds, the
urea units adopt a conformation with the phenyl rings
Figure 3. (colour online) Further intermolecular interactions for L8 (a), L5 (b) and L15 (c).

8
A. CASULA ET AL.
Figure 4. (colour online) main intermolecular interaction for structure L8•DmSo.
Figure 5. (colour online) main intermolecular interactions for
structure L11•2DmSo•DmF. DmSo and DmF have been separated
for clarity.
Figure 6. (colour online) receptor-anion interaction and
conformation of receptor L6 in crystal structure of L6-BzO−.
Note: countercation has been omitted for clarity.
detailed description of the crystal packing is reported in
the Supporting Information.
minimising the repulsion of the iodo substituent, the BzO−
species is slightly shifted on the side of the nitro-phenyl
ring, using one oxygen of the carboxylate group to interact
with the two urea NH donors through a bifurcated N–H⋅⋅⋅O
hydrogen bond. The second oxygen forms a C–H⋅⋅⋅O inter-
action with one aromatic CH of the nitro-phenyl ring (H⋅⋅⋅O
distance is 2.46 Å, C⋅⋅⋅O distance is 3.364(4) Å, see Figure 6).
In the adduct L6-BzO− the urea NH groups are involved
in the formation of strong N–H⋅⋅⋅O hydrogen bonds with
the BzO− guest (H⋅⋅⋅O distances are 1.92(4) and 2.10(4) Å,
N⋅⋅⋅O distances are 2.717(3) and 2.878(3) Å). Interestingly,
in this case the receptor molecule has a non-planar con-
formation with the phenyl rings slightly tilted with respect
the urea plane. Accordingly, no intramolecular C–H⋅⋅⋅O
interactions are observed between the urea C=O group
and aromatic CHs in the ortho positions of the phenyl
rings. This can be explained considering that in order to
have a planar conformation stabilised by intramolecular
C–H⋅⋅⋅O interactions, the receptor must have the substi-
tuted group in an ortho position and both on the same
side of the urea NHs. Such a case would present signifi-
cant steric hindrance or electronic repulsion towards the
anionic guest. Accordingly, the best compromise seems
to be a tilted conformation with the I and NO2 group ori-
ented mutually trans and the NO2 group on the opposite
side with respect the urea NHs. As a consequence of this
conformation, in order to interact with the receptor site,
Solution studies
Anion binding affinity of receptors L1-L15 was evaluated
by means of 1H-NMR titrations in DMSO-d6/0.5% H2O
−
towards a set of anions (F−, Cl−, H2PO4 , AcO−, and BzO−,
as their tetrabutylammonium salts). The experimental
data were fitted according to a 1:1 model and the stability
constants (Table 3) were calculated using the WINEQNMR
programme (13).
By means of a COSY (Correlation Spectroscopy) 2D-NMR
experiment it was possible to attribute the correct chem-
ical shift value for each NH proton in the asymmetrical

SUPRAMOLECULAR CHEMISTRY
9
Table 3. Stability constants (Ka/m−1) of the 1:1 adducts of L1-L15 with F−, cl−, h2po4−, aco−, Bzo−, as their tetrabutylammonium salts in
DmSo-d6/0.5% h2o at 300 K.
−
Receptor
H2PO4
Cl−
F−
AcO−
BzO−
L1
1117 1.7%
34.5 0.1%
Deprot.b
2765 1.2%
364 9.3%
L2
L3
L4
L5
L6
L7
L8
L9
L10
L11
231 2.5%
174 6.0%
684 5.9%
17.7 3.6%
Deprot.b
Deprot.b
Deprot.b
Deprot.b
Deprot.b
Deprot.b
Deprot.b
Deprot.b
Deprot.b
Deprot.b
445 11.0%
277 0.6%
136 1.7%
100 1.3%
314 5.9%
123.3 5.9%
87.3 11.0%
3322 1.8%
567 0.9%
425 2.8%
3706 1.0%
780 1.7%
<10
<10
1283 3.5%
Deprot.b
<10
Deprot.b
a
<10
218.0 3.9%
9620 3.8%
1883 8%
a
a
a
a
a
57.8 1.8%
35.2 7.8%
20.6 2.3%
68.6 2.9%
36.8 0.7%
1611 4.3%
13,467 2.3%
6833 30%
(Continued)

10
A. CASULA ET AL.
Table 3. (Continued).
−
Receptor
L12
H2PO4
Cl−
26.2 6.2%
F−
Deprot.b
AcO−
1470 5.6%
BzO−
681 1.6%
a
L13
871.9 32%
52.2 3.3%
Deprot.b
Deprot.b
2608 17%
1980 6.4%
a
L14
33 4.8%
642 4.8%
514 11%
a
L15
14 8.3%
Deprot.b
583.5 23%
301 1.8%
aSignificant downfield shift and broadening of the signals attributed to the urea Nhs suggesting strong interaction.
bDisappearance of the signals attributed to the urea Nhs upon addition of 0.1 equivalent of fluoride, suggesting deprotonation.
receptors L2 and L3 (and, therefore for all the other halo-
genated receptors): the NH proton in close proximity of the
phenyl moiety is downfield shifted with respect to the NH
protons near the 2,4-dichloro phenyl and the 2-iodophenyl
fragments for L2 and L3, respectively.
Stability constants calculated following both NH pro-
ton signals were comparable so we decided to follow the
chemical shift of the NH proton signal in close proximity
of the non-halogenated phenyl ring.
The results observed for the triad L1, L2, L3 are in agree-
ment with the degree of steric hindrance increasing in the
order L3 > L2 > L1. The presence of the chlorine or iodine
atom in an ortho position on the halogenated phenyl ring
with respect to the urea function, for L2 and L3, respectively,
partially obstructs the anion access to the coordination site
of the receptor. Several anion binding studies for receptor
L1 are reported in the literature, in particular recognition
of carboxylates (12b, 14). The stability constants obtained
for the formation of the 1:1 adduct of L1 with acetate and
benzoate at 300 K are consistent with the values reported
by Leito et al. at 298 K (2138 and 661 M−1 for acetate and
benzoate, respectively). The slight difference in values is
probably due to the difference in the temperature at which
the experiments were conducted (300 K in our case, and
298 K for the data reported in the literature).
in the halogen-substituted phenyl rings, causes a decrease
the values of the calculated stability constants compared
to those of L1-L3. This result can be explained in terms of
both steric and electronic effects. In the triad L4-L6 the nitro
group is in close proximity to the urea function and it could
obstruct the anion coordination. AcO− and H2PO4− cause
deprotonation of the receptor L5, presumably because of a
combination of the elctron withdrawing properties of the
nitro group in ortho position that increases the acidity of
the NH proton, and the steric hindrance that disfavours the
anion binding favouring, instead, the competitive depro-
tonation process in the case of basic anions.
In the series of receptors L7-L9 the stability constants
increase with respect to the previous triad L4-L6, probably
due the meta positioning of the nitro group that allows a
more favourable interaction between the anions and the
urea binding site. The interaction of receptor L7 with anion
guests was previously studied by means of UV–visible and
1H-NMR spectroscopy (12, 14), and the values of the sta-
bility constants reported in Table 1 are in agreement with
the literature.
The series of receptors L10-L12 shows the highest stabil-
ity constants among all the receptors bearing a nitro group.
In particular, receptor L10, already known in the literature
(15), displays a good affinity for acetate as confirmed by
the high value of the stability constant (>104 M−1). The rea-
sons for the increasing anion coordinating ability of these
receptors could be ascribed to both steric and electronic
In the triad L4-L6, the presence of the nitro group in an
ortho position with respect to the central urea function, in
addition to the presence of the chlorine and iodine atoms

SUPRAMOLECULAR CHEMISTRY
11
factors. First, the nitro group in the para position with
respect to the active urea should decrease the steric hin-
drance observed for the previous triads (L4-L9), allowing
for easier access of the anion to the pseudo-cavity of the
receptors and for bigger anion like benzoate. Moreover,
an electron- withdrawing nitro group in the para position
should influence in a positive way the coordination prop-
erties of the ligands, increasing the acidity of the urea NH
protons.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This work was supported by Fondazione Banco di Sardegna.
References
The anion binding activity across this series is consist-
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In conclusion, we have described herein the synthesis and
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−
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Acknowledgements
The authors thank the financial support from Fondazione Banco
di Sardegna.

12
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