Squaramide-based tripodal receptors for selective recognition of sulfate anion

Article abstract of DOI:10.1039/c3cc00196b

Squaramide-based tripodal anion receptors 1-3 have been prepared and their anion binding properties with various inorganic anions were investigated. Receptor 1 formed a dimeric complex in solid state and a 1:1 complex in solution with SO₄^2-. All receptors 1-3 could selectively encapsulate SO₄^2-via hydrogen bonds over other examined anions. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c3cc00196b

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Squaramide-based tripodal receptors for selective
recognition of sulfate anion†
Cite this: Chem. Commun., 2013,
49, 2025
Can Jin, Man Zhang, Lin Wu, Yangfan Guan, Yi Pan, Juli Jiang,* Chen Lin* and
Leyong Wang
Received 22nd November 2012,
Accepted 18th January 2013
DOI: 10.1039/c3cc00196b
www.rsc.org/chemcomm
Squaramide-based tripodal anion receptors 1–3 have been pre- Morey et al. have recently reported the squaramide-ammonium
pared and their anion binding properties with various inorganic based tripodal receptors for the recognition of organic carboxy-
anions were investigated. Receptor 1 formed a dimeric complex in late anions,15c,f and Gale et al. have successfully applied squar-
solid state and a 1 : 1 complex in solution with SO42À. All receptors amides to be potent transmembrane anion transporters which
1–3 could selectively encapsulate SO4 via hydrogen bonds over performed better than (thio)urea analogues.16 Ever since the
2À
other examined anions.
first tren-based tris-(thio)urea receptors were reported for the
anion recognition in 1995,17 very little work has been reported
Sulfate anions play important roles in both biological and on the construction of squaramide-based tripodal receptors
environmental systems.1 Therefore, the design and synthesis with a tren scaffold for the anion recognition,15c,f especially
of artificial receptors bearing amide,2 pyrrole,3 urea,4 thiourea5 for the inorganic anion recognition. Therefore, inspired by the
2À
and indole6 for selective binding of SO4 have emerged into stronger H-bond donor ability of squaramide moiety and the
considerable interest recently. The (thio)urea based tripodal reported calculation results18 that tripodal receptors could
molecules consisting of three arms with complementary geometric effectively bind to tetrahedral inorganic anions such as sulfate
structures could well chelate or encapsulate guests via multiple and phosphate ion, we prepared a series of squaramide-based
H-bonds, which are employed in consideration of selective tripodal receptors 1–3 (Fig. 1a) to investigate their binding
recognition for the challenging tetrahedral geometry and high behaviours for inorganic anions in comparison with reported
hydrophilicity (DGh = À1080 kJ molÀ1)7 of SO42À in nature. For urea-based tripodal receptors.
example, Custelcean et al.8 and Wu et al.9 developed acyclic
The synthesis of receptors 1–3 was achieved in one step from
tris-(2-aminoethyl)amine (tren)-based tris-urea as receptors or tris-(2-aminoethyl)amine using Zn(OTf)2 as a catalyst19 (see
extraction agents for sulfate ions. The Ganguly10 and Das11 ESI†). Efforts were firstly made to evaluate the recognition of
groups have studied synthetic tris-(thio)urea receptors based on receptors for inorganic anionic guests in solid state. The single
a tren scaffold to encapsulate SO42À. Such a tripodal system was crystal X-ray analysis of complex 2TBA-[1ÁSO4] revealed that
also applied for the construction of a triply interlocked capsule unlike those previously reported tripodal capsules with a suitable
2À
with the templated SO4 reported by Beer and coworkers.12
cavity for hosting a guest,9e there was an unusual binding model for
More recently, squaramide, with the strong hydrogen bond sulfate anions (Fig. 1b), where two molecules of tripodal 1 were
donor ability, has been exploited as a functional group in paired with two sulfate anions to form a dimer. The crystal
numerous applications.13 The aromatic squaramide has shown structure showed that three arms of 1 were in a wide open
superiority over urea counterparts due to its stronger H-bond conformation without C3 symmetry, and one of two sulfate anions
donor ability that was enhanced by its conformationally rigid bound two of three squaramide units of one tripodal receptor and
square-shaped structure upon binding,14 so it has been one squaramide unit of the other tripodal receptor through
employed in the design of new anion receptors.15 For example, N–HÁÁÁO hydrogen bonding interactions [NÁÁÁO = 2.652–3.364 Å;
+N–HÁÁÁO = 147.21–171.161], while the other sulfate ion bound in
the opposite way.
Center for Multimolecular Chemistry, State Key Laboratory of Coordination
Chemistry, School of Chemistry and Chemical Engineering, Nanjing University,
Nanjing 210093, China. E-mail: jjl@nju.edu.cn, linchen@nju.edu.cn;
Fax: +86 025 83317761
Additionally, in order to evaluate the binding affinities of
receptors 1–3 with various inorganic anions in solution,
1H NMR titration studies were conducted in DMSO-d6, where
† Electronic supplementary information (ESI) available: Synthesis, NMR experi-
ments, ESI and X-ray crystallographic data in CIF or other details. CCDC 889595.
For ESI and crystallographic data in CIF or other electronic format see DOI:
10.1039/c3cc00196b
halides (ClÀ, BrÀ aÀnd IÀ) and oxo-anions (SO42À, HSO4
,
À
H2PO4À, AcOÀ, NO3 and ClO4À) were investigated as their
tetrabutylammonium salts. The results showed that for
c
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À
the addition of ClÀ and HSO4 ions into the DMSO solution
of receptors 1–3 resulted in moderate chemical shift changes of
N–Ha protons of receptors 1–3 by 0.24, 0.35 and 0.39 ppm, and
0.25, 0.88 and 0.88 ppm, respectively, in 1H NMR titration
experiments (see ESI†), which suggested the weaker binding
affinities of ClÀ and HSO4 to receptors 1–3 than SO42À. The
À
addition of tetrahedral H2PO4 and Y shape AcOÀ ion into the
À
DMSO solution of receptor 1 caused the significantly downfield
chemical shift changes of both squaramide N–Ha and N–Hb
protons of receptor 1 by 1.51 (N–Ha) and 1.39 (N–Hb) ppm, and
1.29 ppm (N–Ha) and 1.25 ppm (N–Hb), respectively, indicating
the superior complementary geometric tripodal scaffold for
better selective recognition of tetrahedral anion than Y shape
one. However, in the cases of receptors 2 and 3 in DMSO
solution, upon addition of H2PO4À and AcOÀ ions, respectively,
the 1H NMR spectra showed that the peak of N–Hb protons
became broadened and even disappeared (see ESI†), suggesting
Fig. 1 (a) Molecular structures of tris-(squaramide) receptors 1–3; (b) the X-ray
structure of 2TBA-[1ÁSO4] depicting the H-binding interactions of two disordered
SO42À with two tripodal molecules. Only one set of H-bonds are shown for each
sulfate cluster and counter cations are omitted for clarity.
À
that receptors 2 and 3 with H2PO4 and AcOÀ in solution
underwent a deprotonation process.22 Furthermore, TBAOH
as a much stronger base was titrated into the DMSO solution
of receptors 2 and 3, respectively, to confirm such deprotonation
process (Fig. S25–S26, ESI†).
receptors 1–3, chemical shift changes or disappearance of both
squaramide N–Ha and N–Hb signals were all observed upon
The binding affinities of receptors 1–3 with those different
anions were assessed (Table 1) using WinEQN MR223 software
by fitting the largest chemical shift of the N–H proton
resonance of the squaramide moieties (see ESI†).22 Generally,
in all cases of receptors 1–3, the binding constants obtained for
SO42À (log K 4 4.75) were higher than H2PO4À and HSO4À, and
much higher than AcOÀ and ClÀ, demonstrating the advantage
of such tripodal scaffold to selectively chelate SO42À. In receptors
1–3, receptors 2 and 3 demonstrated the better binding affinity
for SO42À than receptor 1 due to the electron withdrawing group
attached to their phenyl groups. These obtained strong binding
addition of ClÀ, SO42À, HSO4À, H2PO4 and AcOÀ, which,
À
À
however, were negligible upon addition of BrÀ, IÀ, NO3 and
ClO4À, indicating that receptors 1–3 showed strong binding
affinitiÀes or acid–base4b interactions to ClÀ, SO42À, HSO4
,
À
H2PO4 and AcOÀ. The 1H NMR titration experiments of
2À
receptor 1 with SO4
at different concentrations (0.5, 1.0,
5.0, 10.0 mM) were conducted, and the similar chemical shift
changes of squaramide N–Hs were observed (Fig. S7–S10, ESI†)
in all cases, indicating the same binding behaviour of receptor
2À
1 with SO4 in solutions over a wide range of concentrations.
2À
2À
And then the pure receptor 1 and 1-SO4 complex in solution
affinity from receptors 1–3 showed obvious superiority for SO4
were investigated by 2D NOESY NMR experiments in DMSO-d6,
recognition compared to reported urea-based tripodal receptors,
such as phenyl-substituted tripodal urea (log K = 3.48)17 or
p-cyanophenyl-substituted tripodal urea (log K = 4.70).20 Receptor
1 could also more strongly bind to tetrahedral H2PO4À ion with the
binding constant log K = 4.15 compared to reported phenyl-
substituted tripodal urea receptor (log K = 4.04),17 while recÀeptors
2 and 3 underwent the deprotonation process with H2PO4 ion.
Considering the significant differences in the anion binding
behaviours between our squaramide-based tripodal receptors 1–3
and those well-explored urea tripodal receptors, such receptors 1–3
appeared to show evident improvement for the inorganic anion
respectively, to demonstrate the hydrogen bonding formation
2À
between N–Ha,b of squaramide moieties and SO4 (Fig. S28,
2À
ESI†).11,20 The 1 : 1 binding ratio of receptor 1 and SO4 in
solution was supported by both Job Plot (Fig. S8, ESI†) and
HR-ESI-MS experiments (Fig. S35, ESI†). Since the binding
2À
stoichiometry of receptor 1 and SO4 ion in solid state was
2 : 2, in order to investigate its binding stoichiometry, 1 : 1 or
2 : 2, in solution, a series of DOSY NMR experiments21 were
applied for such investigation. All resulting DOSY NMR spectra
(Fig. S29–S33, ESI†) showed that no diffusion coefficient of
dimeric complex of 2TBA-[1ÁSO4] was found, which indicated the
dimeric structure does not exist as a stable complex in solution
under such conditions, and suggested a 1 : 1 binding stoichiometry
Table 1 Binding constants (log K/MÀ1) of receptors 1, 2 and 3 with various
a
anions determined from NMR titrations in DMSO-d6
2À
between receptor 1 and SO4 in solution (Fig. S34, ESI†).
Anionb
Receptor 1
Receptor 2
Receptor 3
Similar distinct changes of chemical shifts of receptors 2
and 3 upon addition of SO42À in DMSO solution from 1H NMR
titration studies were also observed with the case of receptor 1
with SO42À, where the downfield chemical shift changes of
N–Ha protons were 1.70 ppm and 1.74 ppm, respectively
(Fig. S15 and S20, ESI†), which was larger than that of receptor
1 (1.68 ppm, Fig. S8, ESI†) due to the effect of the electron
withdrawing groups attached to phenyl groups. Moreover,
2À
SO4
4.75 Æ 0.11
4.15 Æ 0.14
3.65 Æ 0.12
2.82 Æ 0.07
2.58 Æ 0.08
4.95 Æ 0.12
N/Ac
4.87 Æ 0.07
N/Ac
À
H2POÀ4
HSO4
AcOÀ
ClÀ
3.78 Æ 0.05
3.65 Æ 0.14
N/Ac
N/Ac
2.61 Æ 0.11
2.65 Æ 0.09
a
Data was best fitted in 1 : 1 binding stoichiometry and see ESI† for
experimental details. Anions used as tetrabutylammonium salts.
Deprotonation behavior was observed.
b
c
c
2026 Chem. Commun., 2013, 49, 2025--2027
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In conclusion, we have developed three squaramide-based
tripodal anion receptors 1–3, and receptor 1 formed dimeric
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.
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We gratefully thank the financial support of National
Natural Science Foundation of China (No. 21102073,
21072093) and the Natural Science Foundation of Jiangsu
(BK2011551). We also gratefully thank referees for helpful
suggestions to improve this article.
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