Anion binding with biphenyl-bis-urea derivatives: Solution and solid-state studies

Article abstract of DOI:10.1039/d0nj03670f

In this work, we have synthesized and characterized bis-urea derivatives 1-3, featuring a biphenyl spacer, and studied their anion binding properties in DMSO solution and in the solid state. In solution, 1?:?1 complexes were observed with association cons

Full text of DOI:10.1039/d0nj03670f

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Anion Binding with Biphenyl-bis-Urea Derivatives: Solution and
Solid-State Studies
Toni Grgurić,a Mario Cetina,b Manuel Petroselli,c Corrado Bacchiocchi,d Zoran Dzolić a* and Massimo
Received 00th January 20xx,
Accepted 00th January 20xx
Camettic*
DOI: 10.1039/x0xx00000x
In this work, we have synthesized and characterized bis-urea derivatives 1-3, featuring a biphenyl spacer, and studied their
anion binding properties in DMSO solution and in the solid state. In solution, 1:1 complexes were observed with association
constants K values in the 103 – 104 M-1 range with a general preference for acetate over dihydrogenphosphate for all three
receptors. We were also able to obtain and characterize by X-ray diffraction on single crystals ten receptor-anion complexes
including acetate, dihydrogenphosphate, but also monohydrogenphosphate, halides and the nitrate ion. Linear (anion-
receptor)n arrays, porous frameworks and non-centrosymmetric structures were observed and described in details.
Introduction
In the field of supramolecular chemistry, anion recognition was
explored only at a later stage, however, it has nowadays fully
caught up and it has decisively become a mature research area.1
Anionic species play an important role in many different aspects
of modern society, in biology, medicine, and in the
environment. The formation of the host-guest receptor-anion
complex is controlled by an often-subtle interplay of several
factors, including the structural and electronic complementarity
between the two interacting partners, and many receptor
designs comprising a large variety of different classes of
compounds have been proposed and tested.2 A lot of attention
was devoted to the design of neutral receptors which could aim
to replicate the effectiveness of biological anion binders and
transporters,3 viz., proteins. These natural chemical wonders
work almost exclusively by making use of hydrogen bonds (HBs),
and thus synthetic receptors based on HB capabilities were
extensively investigated. Among HB receptors, urea derivatives
occupy a prominent role.4 The urea moiety can donate two
parallel HBs to oxoanions (i.e., phosphate or acetate) or two
bifurcate HBs to monoatomic anionic species (i.e., halides),
forming an eight- or six-membered ring, respectively (Scheme
1).
Scheme 1. Modalities of urea – anion binding and molecular formulae
of bis-urea receptors 1-3.
More than one urea group could be also combined onto the
same molecular scaffold, and examples of multi-urea receptors
have been proposed aiming at increasing binding affinity by a
cooperativity effect, or for enhancing the receptor
preorganization and complementarity.5 One particular family of
urea derivatives is that composed of species having two urea
units, and there exists quite a number of reports dealing with
the anion binding properties of these derivatives.6
In this work, bis-urea receptors 1-3 (Scheme 1) have been
synthesized. They all feature a biphenyl spacer separating the
two substituted urea moieties, which was selected to increase
the distance between HB units and to add higher
conformational freedom - due to facile rotation along the
biphenyl C-C bond
- compared to simple analogous
a. Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia. E-mail:
zoran.dzolic@irb.hr
derivatives.6a,c, e-g Receptors 1-3 instead differ for their terminal
substituents, electron-rich, in the case of the phenyl and
naphthyl derivatives 1 and 3; and electron deficient (due to the
electron withdrawing effect of -NO2 group) in 2. We have
assessed their anion binding capability in DMSO solution
towards acetate and dihydrogen phosphate by UV-vis titration
experiments, also pointing out an interesting effect in the case
of the often peculiarly behaving fluoride ion. DFT calculations
b. University of Zagreb, Faculty of Textile Technology, Department of Applied
Chemistry, Prilaz baruna Filipovića 28a, 10000 Zagreb, Croatia.
c. Department of Chemistry, Materials and Chemical Engineering “Giulio Natta”,
Politecnico di Milano, Via Luigi Mancinelli 7, 20131, Milano - Italy. E-mail:
massimo.cametti@polimi.it
d. School of Science and Technology, Chemistry Division, University of Camerino, Via
S. Agostino 1, I-62032 Camerino (MC), Italy.
Electronic Supplementary Information (ESI) available: [X-ray structure descriptions
and Tables (CCDC: 2015334-2015345); additional UV-vis data and DFT
calculations]. See DOI: 10.1039/x0xx00000x
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on anion-receptor complexes stability have been also resulted in negligible effects in the case of X = Cl,VBiewr,AIrtoiclre NOnOlin3e.
DOI: 10.1039/D0NJ03670F
undertaken to complement the experimental data and to Figure 2 a-c shows the absorption changes upon addition of
confirm the binding model adopted for the data analysis. (TBA)H2PO4 to receptors 1-3 and the relative A vs. anion
Furthermore, we were able to obtain single crystal X-ray concentration titration plots (Figure 2 d-f).
structural data for several receptor-anion complexes (with
The corresponding plots for the titrations with (TBA)AcO can
tetrabutylammonium (TBA)X salts X = AcO-, H2PO4 , HPO42-, Br-,
-
-
I- and NO3 ) which demonstrate well the nature of anion-urea
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interactions, show the potential of these system to form infinite
(ligand-anion)n chains and reveal some interesting and
unexpected solid-state architectures.
Results and discussion
Synthesis and X-ray structures of receptors 1-3.
Receptors 1-3 were successfully synthesized by reaction of
the corresponding isocyanate (phenyl isocyanate, p-nitrophenyl
isocyanate and naphthyl isocyanate for receptors 1, 2 and 3
respectively) with 4,4′-diaminobiphenyl in 2:1 molar ratio,
following previously reported procedures for similar
compounds.3b The X-ray structures of receptors 1 and 2 are
depicted in Figure 1 and show in both cases that the urea groups
are oriented in an anti conformation.
In 1, the molecules are self-assembled via two strong
Figure 2. Family of spectra obtained by addition of increasing aliquots of
(TBA)H2PO4 to a 1.66 x10-5 M solution of 1 (a), 2 (b) and 3 (c) in DMSO at
298 K. Relative Abs vs. concentration plots d-f) where lines represent
best fit to a 1:1 binding isotherm.
Figure 1. (a) X-ray structure of 1 showing tape like assemblies formed by
N–H···O HBs, compared to (b) X-ray structure of 2 showing narrow linear
array of molecules formed by CArH···O HBs.
be found in the ESI (Figure S1). In all cases, a red-shift in the
absorption band in the 8 – 14 nm range can be observed, and
importantly, no time dependence was noticed during the
recording (vide infra).
Data could be fitted very well by considering a simple 1:1
binding isotherm. This binding stoichiometry is additionally
corroborated by the concomitant presence of well-defined
isosbestic points (Figures 2 and S1 in ESI). Furthermore, under the
UV-vis titration experimental conditions of dilute receptor (ca. 10-5
M), the formation of 2:1 or 1:2 receptor:anion adducts is significantly
less-favoured. Results, summarized in Table 1, show that K values
are in the 103 – 104 M-1 range with a general preference for
acetate for all three receptors.
bifurcated N–H···O(=C) hydrogen bonds (H···O = 2.08 and 2.13
Å) connecting the two urea groups with the carbonyl oxygen of
a neighbouring molecule, so generating extended molecular
stripes (Fig. 1a), mutually parallel and running along the b-axis.
The X-ray structural analysis of 2 reveals a completely different
set of interactions, as the urea units of nearby receptors do not
interact as in 1. Rather, receptors pair together via mutual
interactions between the urea carbonyls and an activated CHAr
(in α position to the NO2 group; CAr-H···O(=C) distances of 2.57
and 2.59 Å). We also notice that the whole molecule is definitely
more planar with the urea group approximately on the same
plane of the terminal phenyl rings, while dihedral angles
between urea group atoms and the rings of biphenyl moiety are
slightly bigger, from ca. 13 to 26°.
Solution studies.
The anion binding ability of urea derivatives 1-3 were
evaluated by UV-vis titration experiments. Addition of
increasing amounts of (TBA)X (X = H2PO4, AcO, Cl, Br, I, NO3)
salts to a 1.66 x 10-5 M solution of each urea compound induced
significant absorption changes when X = H2PO4 and AcO, while
2 | J. Name., 2012, 00, 1-3
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Table 1. Association constants K (M-1) and corresponding G°exp
DOI: 10.1039/D0NJ03670F
(kcal/mol) measured by UV-vis titration in DMSO at 25°C.
Acetate Phosphate
G°exp
K
K
G°exp
8
9
1
2
3
1800 ±100
4.42
5.67
4.72
1400±30
11000±180
880±30
4.27
5.49
4.00
15000±800
3000±200
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same experimental conditions used for the previously
mentioned titration experiments, are shown.
These data were then compared with the changes recorded
instead after a delay time of 5 minutes upon each fluoride
addition, in Figure 3b. The different behaviour is quite striking.
Under the faster recording conditions, at least two different
processes are evident, one of which involves the appearance of
the shoulder in the 350-400 nm region. This can be attributed
to a deprotonation step which generates a monoanionic urea
species. Since receptor 1, nor its acetate and phosphate
Figure 3. Family of spectra obtained by addition of increasing aliquots of
(TBA)F to a 1.66 x10-5 M solution of 1 (a), and after waiting 5 minutes
after each addition (b) in DMSO at 298 K. Relative Abs vs. concentration
plots for the fast and delayed procedures c) and d), respectively.
While the influence of the NO2 group in enhancing of
approximately one order of magnitude the binding was clearly
expected, the reason for the observed effect of naphthyl vs.
benzyl substitution is less straightforward. In fact, there is a
approx. 2-fold increase in the K values for binding of acetate,
while a decrease is observed for the phosphate ion. The
naphthyl derivative 3 is expected to be a little better binder by
considering the expectedly slightly more acidic urea groups,
however, probably steric effects are predominant in the case of
phosphate ion (vide infra). Additional NMR titrations were not
carried out. Detailed NMR studies of anion binding to the urea
moiety have indeed been already reported.6c At variance with other
cases,7 for receptors 1-3, being the two binding sites acting not
cooperatively, we were not expecting any effect of the binding to
their conformational freedom.
complexes, absorb appreciably at
 > 350 nm, this finding also
confirms the correctness of considering a pure 1:1 binding
model to interpret the association data recorded with acetate
and phosphate anions. TD-DFT calculations for ligand 1 and its
deprotonated form [1-H]- were undertaken (Fig. S2, ESI) to
confirm the presence of a deprotonated species during the
titration of 1 with fluoride. Absorption maximum (max) at 376
nm is predicted by DFT calculation for [1-H]-, while the
maximum for 1 is predicted at 317 nm. Calculations made on
the [1-AcO]- and [1-H2PO4]- complexes results in predicted max
of 327 nm and 323 nm respectively (max ca. 6 - 10 nm).10 This
finding confirms the partial formation of [1-H]- anion during the
course of the titration with fluoride.
On the other hand, we were quite surprised to observe that
by performing the titration experiment waiting 5 minutes after
each addition, the absorption changes (Fig 3b) are different and
they resemble those seen for the other ions, acetate and
phosphate. Indeed, the 350-400 nm region does not show
significant absorption. This phenomenon is probably related to
equilibria with a slower kinetic, probably involving water, which
reduce the anionic urea concentration (viz., by a re-protonation
step), thus rendering the apparent overall process mainly a
binding event. Partial data fitting with a 1:1 binding model of
the lower fluoride concentration region provides a K value of
2500 ± 200 M-1, which however should be considered just semi-
quantitative, for all the additional uncertainties said above.
A separate discussion needs to be undertaken for the
fluoride anion. Binding of fluoride has attracted a lot of interest
over the last years due to its importance in several human
pathologies and in environmental pollution issues, and a multitude
of systems have been tested for this purpose.8 One specific
feature of fluoride ion is represented by its high basicity in polar
aprotic solvents, such as DMSO, and by the exceptional stability
-
of the HF2 (bifluoride) ion. This combination makes fluoride
able to deprotonate many relatively little acidic receptors with
ease. In some cases, this complication renders data
interpretation more problematic and there are several cases of
clearly erroneous data analysis. On the other hand, the
deprotonation step often induces conspicuous changes in the
absorption of the receptor, making it easily discernible in
comparison with a pure binding process. In the case of activated
urea derivatives, a double deprotonation can also be achieved.9
In Figure 3a, the Absorbance changes recorded upon
addition of (TBA)F to a 1.66 x 10-5 M solution of 1, under the
DTF calculations.
Calculations on the stability of the acetate and
dihydrogenphosphate complexes with receptors 1-3 were
performed at the DTF 6-311G+(d,p) level of theory considering
a continuum solvent model for DMSO (ESI). We have also
calculated the stability of their complex with DMSO molecule.
In the case of receptor 3, two possible conformations have been
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found plausible (conf. A and conf. B), depending on the
orientation of the naphthyl group. Calculations showed that
conf. A is just slightly more stable than conf. B and thus we have
considered the stabilization energies for the acetate and
phosphate complexes for both receptor conformations.
Geometries of all complexes at DTF 6-311G+(d,p) level of theory
are shown in Figure 4. In all cases, complexation with the anion
induces small changes in the receptors conformation (ESI).
View Article Online
DOI: 10.1039/D0NJ03670F
Table 2. Stabilization energies E and Ea at 6-311G+(d,p) level of
theory (kcal/mol).
Receptor
E Acetate (E)
13.4 (4.2)
E Phosphate(E)
10.7 (1.5)
EDMSO
9.2
1
2
15.8 (5.7)
12.6 (2.5)
10.1
9.0
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3 conf. A
3 conf. B
12.8 (3.8)
11.0 (2.0)
13.0 (4.6)
10.6 (2.2)
8.4
a E = Eanion - EDMSO
The relative trend for stabilities of the three anion-receptor
complexes is maintained, with 2 best binder in the series for
both phosphate and acetate. Indeed, more positively charged
hydrogens have been found in 2 with respect to 1 or 3, clearly
due to the presence of electron-withdrawing group (See Fig 3S
and Table S1 in ESI). Computed data also confirm the general
preference of 1-3 for acetate compared to phosphate.
In order to have a more quantitative assessment of the
energies in play, we have also calculated stabilization energies
for the complexes with DMSO (Table 2, far right column). Within
the rough approximation
association Gibbs energies for anion complexation
considering the term E = ( Eanion EDMSO) ≈ G°anion. By doing
so, there is a quite remarkable agreement between the 
values found for acetate (Table 2) and the corresponding
experimental values G°exp (Table 1).
E ≈

G°, we can determine apparent
Figure 4. Ball & stick representations of the anion-receptor complexes

G°anion by
obtained by DFT calculations at the 6-311G+(d,p) level of theory. a)
1
1
-
-

-


AcO; b)
phosphate; f)
-phosphate – conf. B.
2
-AcO; c)
3
-AcO – conf. A; d)
3
-AcO – conf. B and e)
E
2
-phosphate; g)
3
-phosphate – conf. A; h)
3

At variance with that, phosphate binding is significantly
underestimated by calculation, furthermore 3-H2PO4 is found to
be more stable than the corresponding 1-H2PO4, and almost as
stable than 2-H2PO4.
Interestingly, receptor 3 conf. A represents the only case
where the phosphate oxoanion is not bound by double parallel
HBs, rather the urea NH groups both bind to a single phosphate
oxygen. This is clearly due to the presence of the second ring of
the naphthyl group, which is found to be involved in CH∙∙∙Ophosp
interactions with the anion. Comparison between HB distances
in acetate and phosphate complexes among 1-3 portends the
occurrence of stronger HB interactions for 2, followed by 3 and
then 1, with a difference between the two NH∙∙∙O distances
more marked for 2, due to the strong electronic effect of the
NO2 group.
-
X-ray analysis of 1-3 / (TBA)X co-crystals (X = AcO-, H2PO4 ,
HPO42-, Br-, I- and NO3 ).
-
We were able to obtain good quality single crystals for a
number of co-crystals with 1-3 and several different anions, by
slow evaporation of a DMSO (or DMF) receptor solution with an
excess of the corresponding tetrabutylammonium salt. For this
reason, we expected to obtain complexes where each urea
group is interacting with an anion. Our solid-state data
collectively confirm that the urea group is always involved in the
main anion-receptor interaction. No cooperation of receptor
units in binding anions is observed, as they are surrounded by
up to three TBA cations. The only exception is represented by
Table 2 summarizes the calculated stabilization energies E
(kcal/mol) for all receptor-anion and receptor-DMSO
complexes.
2-
the HPO4 case (vide infra), where the dianion is interacting
with four urea units belonging to four different receptors. Also,
in all cases, except in (1-((TBA)I)2-DMSO],), the receptor is found
in anti-conformation. Finally, among the ten complex structures
reported, two of them, [1-((TBA)AcO)2-H2O and 1-((TBA)I)2-
DMSO], crystallized in a chiral space group.
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interaction arises from an aromatic CH of the nearby ring, as
View Article Online
DOI: 10.1039/D0NJ03670F
Comparative structural analysis of the complexes between seen in Figure 5b (CAr-H···O = 2.43 Å, Table S7, ESI).
1-3 and (TBA)AcO.
Receptors molecules are linked via typical mutual CAr-
H···ONO2 hydrogen bonds, so forming 2D sheets (Fig. S7a, ESI), as
Complex [1-((TBA)AcO)2-H2O] crystallized in chiral space commonly seen for nitroarene compounds.11 TBA cations are
group P21. The urea groups are disposed in anti-fashion and the clearly involved in close contacts via CTBA–H···O and CTBA
–
9
H···ONO2 HBs, as well as CTBA–H∙∙∙π interactions, (Fig. S7b, ESI),
with closest cation-anion distance of 4.700 Å.
biphenyl moiety feature a ca. 28°  torsion angle (Table S5, ESI).
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Each urea group effectively binds one acetate anion via two
N-H···O HBs with distances (NH···O = from 1.95 to 2.01 Å, Table
S6, ESI) which correspond to reduction of the sum of the van der
Waals radii of interacting atoms of ca. 26-28 % (Figure 5a).
Contribution of adjacent aromatic CHs (CAr-H···OAcO 2.53–2.67 Å,
Table S6, ESI) is also observed. Water molecules acts as bridging
units and bind neighbouring acetates with two Ow-H···OAcO HBs
Complex [3-((TBA)AcO)2] presents some significant
differences with respect to the other two acetate complexes.
The urea groups bind the acetate ions in a way that the plane of
the ion forms a ca. 80° with that of the urea unit (to be
compared with those related to [1-((TBA)AcO)2-H2O] and [2-
((TBA)AcO)2)], of ca. 17 to 27°, respectively), as seen in Figure
5c. Also, only one acetate oxygen is mainly involved in the HB to
the receptor, via two NH···OAcO (H···O = 2.05 and 2.16 Å, Table
S7, ESI) and one CAr-H···OAcO (H···O = 2.44 Å, Table S7, ESI). The
effectiveness of this naphthyl contribution can simply be
evaluated by comparison with the CAr-H···OAcO seen previously
(H···O = 2.53–2.67 Å in 1 and 2.43 Å for 2). Receptors are not
interacting with each other, although they are arranged in
columns along the a-axis. TBA cations are positioned in the inter
columnar space (Fig S8, ESI), and show CTBA-H···OAcO HB with
closest cation-anion distance of 4.889 Å. Hirshfeld surface
analysis12 on the acetate ions of the three complexes (Figure 5d-
f) indicates that in [1-((TBA)AcO)2-H2O] the acetate is mainly
involved in the HB with 1 and the nearby water molecule. In [2-
((TBA)AcO)2], the acetate shows the H-bonding with the urea
groups as prominent, however it also features a multi-point
interaction surface, indicating a closer involvement with the
other elements of the packing. Different pattern, as said, is
noticed for the ion in [3-((TBA)AcO)2], due to the disproportion
of interactions among the two acetate oxygens, as only one is
H-Bonded to the urea group.
Figure 5. CPK representations of X-ray structures of a) [1-((TBA)AcO)2],
b) [2-((TBA)AcO)2 and c) [3-((TBA)AcO)2], showing binding of acetate to
the receptor molecule by NH···O and CH···O hydrogen bonds;
Hirshfeld surface analysis for the acetate ions in d) [1-((TBA)AcO)2], e) [2-
((TBA)AcO)2 and f) [3-((TBA)AcO)2].
Complex with trigonal nitrate anion: [1-((TBA)NO3)2].
The complex crystallized in monoclinic space group P21/c.
The asymmetric unit contains half receptor, one TBA cation and
one nitrate anion (Fig. 6a). Also in this case, we observe a 1:2
ligand:anion complex, where two nitrate anions are bound via
two strong NHurea‧‧‧O HBs (2.06 and 2.32 Å, Table S6, ESI).
The nitrate anion does not reside on the same plane of the
urea moiety (46°), probably due to its strong interaction with
the closest TBA cation, positioned at ca. 4.6 Å, also noticeable
by the Hirshfeld surface analysis (Figure 6b). Neighbouring
receptors are engaged in weak CAr-H‧‧‧Ourea hydrogen bonds
parallel to the c-axis, thus forming sheets (Figure 6c). TBA
(2.02 and 2.10 Å), so forming (1-acetate-water-acetate-1)n
infinite chains. These chains are mutually parallel, while TBA
cations are linked to receptors, acetates and water molecules
by
CTBA-H···O(=C), CTBA-H···OAcO, CTBA-H···Ow and CTBA-H∙∙∙π
interactions, with closest cation-anion distances of 4.697 and
4.390 Å. Overall, the packing consists in TBA cations inserted
between layers of HB chains (Fig. S6, ESI).
Complex 2-((TBA)AcO)2, crystallized in monoclinic space
cations and nitrates, displaying contacts attributed to CTBA-
H‧‧
group C2/c, shows a receptor molecule more evidently bent (

‧
ONO2 HBs are forming two sets of symmetry dependent chains
torsion angle is ca. 36°, Table S5, ESI). The urea groups bind
acetate via three HBs, two via the urea NHs with NH···O contacts
that correspond a reduction of the sum of vdW radii of
interaction atoms of ca. 28 and 31 % (Table S7, ESI). A third
parallel to the crystallographic b-axis, where each nitrate is
surrounded by three TBAs (Fig 6d).
To the best of our knowledge, this is the first structural
report of a urea derivative bound to a free uncoordinated
nitrate ion.
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and since each receptor displays an anti conformatVioienw aArnticdlebOinnldines
DOI: 10.1039/D0NJ03670F
two phosphates, flat 1D ribbon-like structures are generated
(Figure 7a).
Urea anion HB interactions (N–H···O 1.92 and 2.18 Å, Table
S6, ESI) are responsible for a reduction of the sum of the vdW
radii of interaction atoms of 31.9 % (Table S6, ESI). The packing
is also characterized by CTBA-H···OH2PO4 within the ion pair
(shortest P···N distance of 5.418 Å) and additional interactions
between the TBA cation and 1 (CTBA–H···Nurea hydrogen bonds
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and
CTBA-H∙∙∙π interactions). Interestingly, the previously
mentioned ribbons assemble into
a
complex packing
architecture where the linear phosphate arrays are wrapped by
the receptor molecules forming a channeled structure aligned
along the a-axis. (Fig. 7b). Furthermore, hydrophobic channels
can be observed along the c-axis. They are filled with heavily
disordered molecules of solvent(s), and virtually amount to ca.
9.4% of potential void space.13
Crystallization of 2 with (TBA)H2PO4 led to an unexpected
outcome. Indeed, two receptor molecules, two TBA cations and
one phosphate anion were found in the asymmetric unit. This
implies the presence of dianionic monohydrogen phosphate,
Figure 6. a) CPK representations of X-ray structures of [1-((TBA)NO3)2],
showing nitrate binding by NH···O and CH···O HBs, (b) Hirshfeld
surface analysis of nitrate ion, (c) network of HBs that link neighbouring
receptors, and (d) assembly motifs related to TBA cations / nitrate
anions pairs.
-
HPO42-, instead of H2PO4 and suggested that an anion-anion
proton transfer process, a phenomenon already described a
decade ago by Gale et al.,14 has occurred. Urea units are found
in a syn conformation and each anion is entrapped between
four molecules of 2, which establish a total of eight strong
NH···O hydrogen bonds with the anion (H···O = 1.92-2.52 Å,
Table S7, ESI), further reinforced by two weak CH···O HBs (H···O
= 2.25 and2.36 Å, Table S7, ESI), as seen in Figure 8a.
Complexes with tetrahedral anions: [1-((TBA)H2PO4)2] and
[(2)2-(TBA)2HPO4)].
In
complex
[1-((TBA)H2PO4)2],
disordered
dihydrogenphosphate anions are found to form 1D chains
which align on the a-axis direction, as they mutually interact by
O-H···O HBs. Each phosphate is bound to a receptor molecule,
Figure 8. a) CPK view of the X-ray structure of [2-((TBA)2HPO4] showing
the dihydrogen phosphate dianion interacting with four receptors; (b)
view of the linear arrays based on the anion/receptor recognition.
position of receptor molecules.
Figure 7. (a) Ball & Stick representations of X-ray structures of [1-
((TBA)H2PO4)2], showing NH···O and CH···O HBs linking dihydrogen
phosphate anions and 1; (b) view of the packing of [1-((TBA)H2PO4)2]
viewed along the b axis, c) view of the packing of [1-((TBA)H2PO4)2]
TBA cations reside in the vicinity of the dianion (closest N···P
distance equals to 4.697 Å), on opposite sides within the
available interstices on the side of the linear arrays, and they
linked to the anion by one CTBA-H···OHPO4 HB (Fig S11c, ESI).
Neighbouring receptor molecules are linked by mutual CAr-
H···ONO2 hydrogen bonds (Fig S11b, ESI),10 but also with one C-
viewed along the
c axis, showing potentially porous structure.
Dihydrogen phosphate anion is disordered and only the major
component is shown.
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H∙∙∙π and four π∙∙∙π interactions, TBA cations are further linked
to receptors by five CTBA-H···O(=C), five CTBAH···ONO2 HBs and one
CTBA-H∙∙∙π interactions (Figure S11, ESI). Dihedral angle between
neighbouring receptor molecules is ca. 44°. Interestingly,
phenyl rings of biphenyl moiety in both independent receptor
to [1-((TBA)Br)2], in the (TBA)I case, one CAr−H··· VinietweArraticclteiOonnlinies
responsible for the self-assembling of neighbouring receptors of
DOI: 10.1039/D0NJ03670F
1. The receptor molecules, cations and anions are additionally
linked by CTBA-H···I and CTBA-H···Ourea HBs. Thus, the packing
consists of sheets of doubly charged [1-(I)2]2 units, all oriented
in the same direction, with TBA cations segregated within them,
giving rise to a chiral environment and the formation of two-
dimensional network (Fig. S12b, ESI).
molecules are bent, the  torsion angles being in the range from
ca. 26 to 32° (Table S5, ESI).
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Complexes with spherical anions: [1-((TBA)I)2DMSO], [1-
((TBA)Br)2], [2-((TBA)Br)2], [3-((TBA)Br)2].
As to complexes [2-((TBA)Br)2] and [3-((TBA)Br)2], they
are structurally very similar to 1-((TBA)Br)2]. The urea groups
are arranged in anti fashion (Fig. 9c-d), and they effectively bind
bromide anions via two bifurcated moderately strong N-H···Br
In both complexes with (TBA)Br and (TBA)I, receptor 1 is
more planar with the
 torsion angle only slightly bigger than HBs, which by a metric comparison, are approximately equal in
that in 1. Urea groups are rotated with respect to the internal strength to those in [1-((TBA)Br)2] (reduction of the sum of the
phenyl rings of ca. 13 to 29°, while terminal phenyl rings are vdW and ionic radii = 23 %, Table S7, ESI). In [3-((TBA)Br)2], one
almost parallel with urea groups (Table S5, ESI). In [1- hydrogen atom of naphthyl moiety is also engaged in receptor-
((TBA)Br)2], the receptor binds two bromide ions via two pairs bromide hydrogen-bonding interaction (Fig 9d). The phenyl
of bifurcated N-H···Br hydrogen bonds in anti fashion (Fig 9a). rings of biphenyl moiety are almost coplanar, as well as the urea
Reduction of the sum of the van der Waals radii of hydrogen moiety atoms with terminal phenyl ring. On the other side, urea
atom and ionic radii of bromide anion for the two stronger moiety atoms and internal phenyl ring of biphenyl moiety are
interactions is ca. 21 and 23 % (Table S6, ESI).
twisted, with the dihedral angle value of ca. 26° (Table S5, ESI).
A water molecule is entrapped between one bromide and Dihedral angle values between urea group atoms and phenyl
TBA cation by one Ow-H···Br and two CTBA-H···Ow HBs and, rings in [3-((TBA)Br)2] are approximately equal, but two phenyl
therefore, the environment around the two bromides slightly rings of biphenyl moiety are rotated of ca. 37°, a value which
differs (Fig. S13a, ESI). Receptor, TBA cations, bromides and
water molecules in [1-((TBA)Br)2] are linked by numerous HBs,
represents the biggest
 angle value in all ten structures
reported, and which makes this structure highly bent.
CTBA-H···Ourea, CTBA-H···Br, as well as by one CTBA-H···

interactions
On the other hand, packing in the three (TBA)Br complexes
(Fig. S13b, ESI). Overall, the crystal packing consists of TBA are quite different, and a full description on this regard can be
cations which are sandwiched between charge assisted found in the ESI.
hydrogen-bonded receptor-anion aggregates, which form a
zig-zag like pattern.
Experimental
Materials and Methods.
The chemicals for synthesis were obtained from commercial
sources and used as received without further purification. All
solvents were purified and dried by standard procedures and
distilled prior to use. All the melting points were determined on
a hot-coil stage melting point apparatus and are uncorrected.
FT IR-ATR spectra were recorded using a Fourier Transform-
Infrared Attenuated Total Reflection PerkinElmer UATR Two
spectrometer in the range 400 cm–1 to 4000 cm–1. 1H NMR and
13C NMR spectra were recorded on Brucker Avance AV600
Figure 9. CPK views of X-ray structures of a) [1-((TBA)Br)2]; b) [1-
spectrometer, operated at 600.13 MHz for 1H nuclei and at
((TBA)I)2]; c) [2-((TBA)Br)2] and d) [3-((TBA)Br)2]. Anion receptor binding
and additional solvent molecules (H2O or DMSO) are shown when
150.92 MHz for 13C nuclei, with tetramethylsilane as an internal
standard. Elemental analyses were carried out using an
Elementar vario MICRO cube elemental analyzer.
present.
In [1-((TBA)I)2-DMSO], receptor 1 binds each of two iodide
anions via two bifurcated N–H···I HBs with distances which
correspond to a ca. 20 and 21 % reduction of the sum of the
vdW and ionic radii of the interacting atoms. In this case,
however, the receptor is found in a syn-conformation (Fig.9b),
and a DMSO molecule is found in the lattice. The solvent is
entrapped between the TBA cation and the receptor, hydrogen-
bonded to the carbonyl oxygen by one CDMSO-H···Ourea HB and to
TBA cation by two CTBA-H···ODMSO HB (Fig. S12a, ESI). Compared
1,1'-(4,4'-biphenylene)bis(3-phenylurea) (1).
To a stirring solution of 4,4’-diaminobiphenyl (1.00 g, 5.4 mmol)
in dry dichloromethane, a solution of phenyl isocyanate (1.17
mL, 10.8 mmol) in dry dichloromethane was added dropwise
over a period of 1 h with constant stirring at room temperature.
The mixture was stirred for additional 16 hours at room
temperature as product started to precipitate. After filtration,
the precipitate was washed several times with dichloromethane
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to remove the unreacted reagents. The product was
recrystallized from DMF to yield the pure receptor 1 as a white
crystalline solid (2.14 g)
Yield: 94 %; m.p. = >300 °C; FT-IR (ATR) ṽ/cm−1 = 3300, 1640,
1594, 1578, 1538, 1496, 1443, 1230; 1H NMR (600 MHz, DMSO-
d6) δ/ppm = 8.71 (s, 2H, NH), 8.65 (s, 2H, NH), 7.45-7.58 (m,
12H), 7.27-7.31 (m, 4H), 6.96-6.99 (m, 2H); 13C NMR (151 MHz,
DMSO-d6) δ/ppm = 118.3, 118.7, 122.0, 126.5, 128.8, 133.4,
138.6, 139.7, 152.6. Anal. Calcd for C26H22N4O2: C, 73.92; H,
5.25; N, 13.26; Found: C, 73.88; H, 5.24; N, 13.27.
Conclusions
View Article Online
The binding capabilities of biphenyl-bisDuOrI:e1a0.1d0e3r9i/vDa0tNivJe0s36170-3F
towards common anions in DMSO solution have been
evaluated, confirming the general trend seen in similar types of
compounds, but at the same time, showing that deprotonation
processes in DMSO by acetate and phosphate anions can
probably be disregarded in data analysis, except for the case of
fluoride anion. In the solid state, the large set of X-ray structures
described here demonstrates fully the range of intermolecular
interactions, and supramolecular architectures that can be
achieved by assembly of three mutually interacting
components. Indeed, linear (anion-receptor)n arrays, porous
frameworks, and also non-centrosymmetric structures were
generated.
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1,1'-(4,4'-biphenylene)bis(3-(4-nitrophenyl)urea) (2).
Receptor 2 was synthesized according to above procedure using
4,4’-diaminobiphenyl (1.00 g, 5.4 mmol) and 4-nitrophenyl
isocyanate (1.77 g, 10.8 mmol). The product was isolated and
recrystallized from DMF to yield the pure 2 as a white crystalline
solid (2.35 g).
Conflicts of interest
There are no conflicts to declare.
Yield: 85 %; m.p. = > 300
℃
; FT-IR (ATR) ṽ/cm−1 = 3356, 3321,
1
1722, 1650, 1599, 1564, 1532, 1494, 1321; H NMR (600 MHz,
DMSO-d6) δ/ppm = 9.45 (s, 2H, NH), 8.99 (s, 2H, NH), 8.19-8.21
(m, 4H), 7.70-7.72 (m, 4H), 7.55-7.62 (m, 8H); 13C NMR (151
MHz, DMSO-d6) δ/ppm = 117.5, 119.0, 125.1, 126.5, 133.9,
138.0, 141.0, 146.3, 151.9. Anal. Calcd for C26H20N6O6: C, 60.94;
H, 3.93; N, 16.40; Found: C, 60.96; H, 3.94; N, 16.41.
Acknowledgements
This work has been supported by Croatian Science Foundation
under the project number IP-2016-06-5983. All authors would
like to thank Prof. Kari Rissanen for data collection of complex
[1-((TBA)Br)2]. M. C. thanks MIUR for Fondi di finanziamento per
le attività base di ricerca (FFABR).
1,1'-(4,4'-biphenylene)bis(3-(naphthalen-1-yl)urea)
(3).
Receptor 3 was synthesized according to above procedure using
4,4’-diaminobiphenyl (1.00 g, 5.4 mmol) and 1-naphthyl
isocyanate (1.83 g, 10.8 mmol). The product was isolated and
recrystallized from DMF to yield the pure 3 as a white crystalline
solid (2.31 g).
Notes and references
Yield: 82 %; m.p. = > 300
℃
; FT-IR (ATR) ṽ/cm−1 = 3287, 1650,
1
J. L. Sessler, P. A. Gale and W.-S. Cho, Anion Receptor
Chemistry, Royal Society of Chemistry, Cambridge, 2006; b) P.
A. Gale and W. Dehaen, Anion Recognition in Supramolecular
Chemistry, Springer, Berlin, 2010.
a) P. A. Gale and C. Caltagirone, Coord. Chem. Rev., 2018, 354,
2; (b) P. Molina, F. Zapata and A. Caballero, Chem. Rev., 2017,
117, 9907; (c) N. Busschaert, C. Caltagirone, W. Van Rossom
and P. A. Gale, Chem. Rev., 2015, 115, 8038; d) M. Giese, M.
Albrecht and K. Rissanen, Chem. Rev., 2015, 115, 8867; (e) P.
A. Gale, E. N. W. Howe and X. Wu, Chem., 2016, 1, 351; (f) N.
H. Evans and P. D. Beer, Angew. Chem., Int. Ed., 2014, 53,
11716.
a) C. M. Dias, H. Li, H. Valkenier, L. E. Karagiannidis, P. A. Gale,
D. N. Sheppard and A. P. Davis, Org. Biomol. Chem., 2018, 16,
1083; b) S. A. Kadam, K. Martin, K. Haav, L. Toom, C. Mayeux,
A. Pung, P. A. Gale, J. R. Hiscock, S. J. Brooks, I. L. Kirby, N.
Busschaert and I. Leito, Chem. Eur. J. 2015, 21, 5145 – 5160.
a) V. Blažek Bregović, N. Basarić, N. and K Mlinarić-Majerski,
Coord. Chem. Rev., 2015, 295, 80; b) V. Amendola, L. Fabbrizzi
and L. Mosca, Chem. Soc. Rev., 2010, 39, 3889; c) R.
Custelcean, Chem. Commun., 2008, 295.
a) C. Jia, W. Zuo, D. Zhang, X.-.J Yang and B. Wu, Chem.
Commun., 2016, 52, 9614; b) M. Delecluse, C. Colomban, B.
Chatelet, S. Chevallier-Michaud, D. Moraleda, J.-P. Dutasta
and A. Martinez, J. Org. Chem., 2020, 85, 7, 4706–4711; c) J.
Fu, B. Zheng, H. Zhang, Y. Zhao, D. Zhang, W. Zhang, X.-J. Yang
and B. Wu, Chem. Commun., 2020, 56, 2475; d) X. Fan, D.
Zhang, S. Jiang, H. Wang, L.-T. Lin, B. Zheng, W.-H. Xu, Y. Zhao,
B. P. Hay, Y.-T. Chan, X.-J. Yang, X. Li and B. Wu, Chem. Sci.,
2019, 10, 6278.
1598, 1542, 1497, 1243; 1H NMR (600 MHz, DMSO-d6) δ/ppm =
9.15 (s, 2H, NH), 8.81 (s, 2H, NH), 8.15 (d, J = 8.4 Hz, 2H), 8.04
(d, J = 7.5 Hz, 2H), 7.94 (d, J = 8.1 Hz, 2H), 7.48-7.66 (m, 16H);
13C NMR (151 MHz, DMSO-d6) δ/ppm = 117.4, 118.5, 121.3,
122.9, 125.7, 125.8, 125.9, 126.0, 126.5, 128,4, 133.3, 133.7,
134.3, 138.7, 152.9. Anal. Calcd for C34H26N4O2: C, 78.14; H,
5.01; N, 10.72; Found: C, 78.09; H, 4.97; N, 5.03.
2
General Procedure for UV-vis Titrations. UV/vis spectra were
recorded on a Varian Cary 100 Bio spectrometer in standard
quartz cuvettes (1 cm x 1 cm cross section) at thermostated at
25 °C. Fresh stock solutions of the receptors 1, 2 and 3 and
(TBA)X salts (X = AcO, H2PO4, F, Cl and NO3) were prepared
before each experiment. Typically, 2 mL of DMSO were put into
3
4
5
the cuvette and baseline was recorded. Then 50-100
L of
receptor was added to a final concentration of ca. 1.5 x 10-5 M.
Whereupon, small aliquots of a concentrated anion stock
solution were added to the cuvette containing the receptor, and
UV-vis spectra (in the 250-700 nm) were recorded immediately
after each addition, or after waiting a 5 minutes period. Baseline
and dilution corrections were applied to each absorption
spectrum. Absorbance vs. anion concentration data (for
example, plots in Figs. 2d-f and Figs. S1 d-f) were fitted
considering a 1:1 binding isotherm. Titration experiments were
run in duplicate.
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a) D. Barišić, N. Cindro, M. Juribašić Kulcsár, M. Tireli, K.
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Užarević, N. Bregovic and V. Tomišić, Chem. - A Eur. J., 2019,
18, 4695; b) C. M. Dias, H. Li, H. Valkenier, L. E. Karagiannidis,
P. A. Gale, D. N. Sheppard and A. P. Davis, Org. Biomol. Chem.,
2018, 16, 1083; c) D. M. Gillen, C. S. Hawes and T.
Gunnlaugsson, J. Org. Chem., 2018, 83, 10398; d) L. M. Eytel,
A. C. Brueckner, J. A. Lohrman, M. M. Haley, P. H.-Y. Cheong
and D. W. Johnson, Chem. Commun., 2018, 54, 13208; e) B.
Nayak, U. Manna and G. Das, ChemistrySelect, 2018, 3, 3548;
f) S. Halder, U. Manna and Gopal Das, New J. Chem., 2019, 43,
14112; g) U. Manna, S. Kayal, B. Nayak and G. Das, Dalton
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2020, 44, 2033-2045.
a) M. Cametti and K. Rissanen, Chem. Commun., 2009, 2809;
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9
D. Esteban-Gómez, L. Fabbrizzi and M. Licchelli, J. Org. Chem.,
2005, 70, 5717.
10 The latter max values are in good agreement with the
experimental values of 304 nm, 312nm, and 313 nm and in
line with generally accepted  values between experimental
and calculated data, see for example D. L. Ashford, C. R. K.
Glasson, M. R. Norris, J. J. Concepcion, S. Keinan, M. K.
Brennaman, J. L. Templeton and T. J. Meyer, Inorg. Chem.,
2014, 53, 5637.
11 a) I. L. Kirby, M. Brightwell, M. B. Pitak, C. Wilson, S. J. Coles,
P. A. Gale, Phys.Chem.Chem.Phys. 2014, 16, 10943; b) S. Li, C.
Jia, B. Wu, Q. Luo, X. Huang, Z. Yang, Q.-S. Li, X.-J. Yang,
Angew.Chem., Int .Ed. 2011, 50, 5721.
12 M. A. Spackman and D. Jayatilaka, CrystEngComm, 2009, 11
,
19.
13 Voids were calculated with the Mercury 4.3.1, Probe Radius =
1.2 Å; Approx. Grid Spacing = 0.7 Å
14 P. A. Gale, J. R. Hiscock, S. J. Moore, C. Caltagirone, M. B.
Hursthouse and M. E. Light, Chem. Asian J., 2010, 5, 555.
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