Dual Sensing by Simple Heteroditopic Salt Receptors Containing an Anthraquinone Unit

Article abstract of DOI:10.1021/acs.inorgchem.6b00132

We synthesized simple ion pair receptors consisting of a crown ether cation binding site and an anthraquinone-supported thiourea anion binding domain and studied their anion-, cation-, and salt-binding properties using spectroscopic, spectrophotometric, a

Full text of DOI:10.1021/acs.inorgchem.6b00132

Article
pubs.acs.org/IC
Dual Sensing by Simple Heteroditopic Salt Receptors Containing an
Anthraquinone Unit
Marcin Karbarz† and Jan Romanski*,†
́
†Faculty of Chemistry, University of Warsaw, Pasteura 1, PL 02-093 Warsaw, Poland
S
* Supporting Information
ABSTRACT: We synthesized simple ion pair receptors consisting of a
crown ether cation binding site and an anthraquinone-supported thiourea
anion binding domain and studied their anion-, cation-, and salt-binding
properties using spectroscopic, spectrophotometric, and electrochemical
measurements in acetonitrile solution. Apart from carboxylate anions,
which cause deprotonation, all the anions tested were found to associate
with receptor 1 more strongly in the presence of sodium cations, whereas
in the presence of potassium or ammonium cation the anion binding
strength was greatly diminished. A homotopic anion receptor 3, lacking a
crown ether unit, was unable to bind sodium salt more strongly than
tetrabutylammonium salts. Solution and solid-state X-ray measurements
revealed that strong sodium coordination with the cation-binding domain is responsible for the salt-binding enhancement.
Electrochemical measurements showed that the addition of anions to the receptor 1 pretreated with sodium cations resulted in
greater changes in reduction potentials compared to the addition of anions to receptor 1 in the absence of Na+.
consisting of an anthraquinone-based anion binding site and
a crown ether unit responsible for cation association. The
cation binding site is linked to the receptor platform in a way
that reduces the electron density on the thiourea binding site
and thus enables stronger interaction with anion and ion pairs.
We also discuss in this paper the role of the individual structural
elements on anion and ion-pair binding.
INTRODUCTION
■
Anthraquinones, colored compounds that are good fluoro-
phores, serve as the fundamental construction for many natural
colors found in plants.1 Apart from their optical properties, in
nonaqueous, aprotic media, the quinone system in anthraqui-
none derivatives usually gives two 1 e peaks. The corresponding
̇
̇
processes can be written as AQ + e = AQ¯ and AQ¯ + e =
AQ2−.2 Therefore, anthraquinones are convenient dual-signal-
ing subunits in the construction of sensors able to recognize
both anions or cations. The recognition event in such molecular
receptors involves signaling by optical changes or perturbation
in potential signals. Various receptors have been proposed for
the recognition of anions consisting of amide, urea or thiourea
and imidazole or pyrrole conjugate. Nevertheless, most of these
are selective toward basic anions such as fluoride and acetate
ions.3 Furthermore, an anthraquinone moiety connected to the
receptor scaffold might be useful for cation detection,
producing optical/electrochemical responses toward target
analytes.4 However, ion-pair receptors that are able to
simultaneously recognize cations and anions and bear
anthraquinone moieties displaying the dual-sensing mode are
limited.5 Moreover, the simplest ion-pair receptors displaying
significantly enhanced affinities toward anions in the presence
of cations possess a crown ether unit and a urea or thiourea
group linked together. The crown ether substituent is usually
located in close proximity to the (thio)urea group acting as an
electron-donating group, which may diminish the acidity of NH
protons and as a consequence reduce the hydrogen bond
interaction ability.6
EXPERIMENTAL SECTION
■
All reagents and chemicals were of reagent-grade quality and
purchased commercially. 1H and 13C NMR spectra were recorded
1
on a Bruker 300 MHz spectrometer. H NMR chemical shifts δ are
reported in parts per million referenced to residual solvent signal
(deuterated dimethyl sulfoxide (DMSO-d6) or CDCl3). UV−vis
titrations were performed in acetonitrile using a Thermo Spectronic
Unicam UV500 Spectrophotometer. High-resolution mass spectra
(HRMS) were measured on a Quattro LC Micromass unit using
electrospray ionization (ESI) technique.
Preparation of Compound 4a. To a solution of 3-nitrobenzoyl
chloride (1 g, 5.39 mmol) and 0.9 mL of triethylamine in 50 mL of dry
dichloromethane, 1-aza-18-crown-6 (1.42 g, 5.40 mmol) at 0 °C (ice
bath) was added. The reaction mixture was stirred for 30 min and then
left at room temperature (r.t.) overnight. The organic phase was then
washed twice with distilled water, 1 M HCl, and saturated NaHCO3
and dried over MgSO4. After evaporation of dichloromethane the
residue was purified by silica gel column chromatography (5%
methanol in chloroform) to give the title product as a colorless oil
(2.15 g, 97% yield).
HRMS (ESI): calcd for C19H28N2O8Na [M + Na]+: 435.1743,
found: 435.1747.
Therefore, in this study we synthesized and tested the optical
Received: January 19, 2016
and electrochemical behavior of a simple salt receptor
© XXXX American Chemical Society
A
DOI: 10.1021/acs.inorgchem.6b00132
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1H NMR (300 MHz, DMSO-d6) δ 3.40−3.80 (m, 24H), 7.71−7.77
(m, 1H), 7.80−7.89 (m, 1H), 8.20−8.35 (m, 2H).
1H NMR (300 MHz, DMSO-d6) δ 3.40−3.70 (m, 24H), 7.30−7.45
(m, 2H), 7.51−7.60 (m, 2H), 7.90−7.98 (m, 2H), 8.05−8.28 (m, 4H),
8.44−8.46 (m, 1H), 10.40 (bs, 1H), 10.56 (bs, 1H).
13C NMR (75 MHz, DMSO-d6) δ 45.66, 50.08, 68.71, 70.19, 70.40,
70.64, 122.25, 124.27, 130.60, 133.77, 138.92, 147.97, 169.15.
Preparation of Compound 4b. To a solution of 4-nitrobenzoyl
chloride (1 g, 5.39 mmol) and 0.9 mL of triethylamine in 50 mL of dry
dichloromethane, 1-aza-18-crown-6 (1.42 g, 5.40 mmol) at 0 °C (ice
bath) was added. The reaction mixture was stirred for 30 min and then
left at r.t. overnight. The organic phase was then washed twice with
distilled water, 1 M HCl, and saturated NaHCO3 and dried over
MgSO4. After evaporation of dichloromethane the residue was purified
by silica gel column chromatography (5% methanol in chloroform) to
give the title product as a colorless oil (2.10 g, 95% yield). mp 84−86
°C.
13C NMR (75 MHz, DMSO-d6) δ 66.88, 70.20, 70.40, 70.47,
119.38, 123.37, 127.15, 127.20, 127.38, 127.74, 128.32, 128.61, 133.53,
133.58, 133.63, 134.08, 134.74, 135.08, 140.14, 145.93, 170.98, 179.73,
181.73, 181.88, 182.81.
Anal. Calcd for C34H37N3O8S: C, 63.0; H, 5.8; N, 6.5; S, 5.0%.
Found: C, 62.9; H, 5.6; N, 6.4; S, 4.9%.
Preparation of Receptor 3. To the solution of aniline (54 mg,
0.58 mmol) in 10 mL of dry THF, isothiocyanate 6 (54 mg, 154
mmol) was added. After it was stirred overnight at r.t., the reaction
mixture was concentrated and purified by silica gel column
chromatography (50% hexane in dichloromethane) to give receptor
3 as a yellow solid (160 mg, 77% yield). mp 207−208 °C.
HRMS (ESI): calcd for C21H14N2O2SNa [M + H]+: 381.0647,
found: 381.0675.
HRMS (ESI): calcd for C19H28N2O8Na [M + Na]+: 435.1743,
found: 435.1750.
1H NMR (300 MHz, DMSO-d6) δ 3.40−3.75 (m, 24H), 7.60−7.70
(m, 2H), 8.22−8.35 (m, 2H).
1H NMR (300 MHz, DMSO-d6) δ 7.10−7.25 (m, 1H), 7.30−7.58
(m, 4H), 7.85−8.00 (m, 2H), 8.05−8.30 (m, 4H), 8.47 (s, 1H).
13C NMR (75 MHz, DMSO-d6) δ 119.32, 124.24, 125.49, 127.14,
127.20, 127.30, 128.30, 128.49, 129.14, 133.56, 133.66, 134.07, 134.73,
135.06, 139.44, 146.12, 179.81, 181.89, 182.85.
13C NMR (75 MHz, DMSO-d6) δ 45.59, 49.79, 68.63, 68.82, 70.09,
70.24, 70.39, 70.61, 124.11, 128.55, 143.79, 147.93, 169.56.
Preparation of Compound 5a and 5b. To a degassed solution
of 4a or 4b (2 g, 4.85 mmol) in 150 mL of tetrahydrofuran (THF)/
MeOH (1:4), a catalytic amount of 10% Pd/C was added. The
reaction mixture was kept under H2 atmosphere (balloon pressure) at
r.t. overnight. The catalyst was removed by filtration through a pad of
diatomaceous earth and washed with MeOH. The filtrate was
concentrated under reduced pressure to give the crude product in
quantitative yield (1.85 g). The amine was used in next step without
further purification.
Anal. Calcd for C21H14N2O2S: C, 70.4; H, 3.9; N, 7.8; S, 8.9%.
Found: C, 70.2; H, 3.8; N, 7.8; S, 8.8%.
Electrochemical Measurement. The electrochemical investiga-
tions were performed in a three-electrode cell. The electrode potential
was controlled by CH Instrument, model 700D potentiostat,
controlled via producer’s software. A platinum wire served as the
counter electrode, and a Ag/Ag(I) system (0.1 M AgNO3 acetonitrile
solution) was used as the reference electrode. The supporting
electrolyte was 0.1 M tetrabutylammonium hexafluorophosphate
(TBAPF6) in acetonitrile. A 3.0 mm, in diameter, glassy carbon disk
electrode was used as the working electrode. Before each experiment,
the electrode was polished with aluminum oxide powder of various
size on a wet pad, rinsed with water, and then dried with ethanol. To
minimize the electric noise, the electrochemical cell was kept in a
grounded Faraday cage. More information about electrochemical
measurements are in Supporting Information.
X-ray Measurement. The crystallographic data for 2·NaClO4
were deposited with the Cambridge Crystallographic Data Center as
Supplementary Publication No. CCDC 1438 959. Complex of 2·
NaClO4 was crystallized by slow diffusion of Et2O into acetontrile/
methanol solution. The X-ray measurement of receptor 2·NaClO4 was
performed at 100(2) K on a Bruker D8 Venture Photon100
diffractometer equipped with a TRIUMPH monochromator and a
Mo Kα fine focus sealed tube (λ = 0.710 73 Å). A total of 870 frames
were collected with Bruker APEX2 program.12 The frames were
integrated with the Bruker SAINT software package13 using a narrow-
frame algorithm. The integration of the data using a monoclinic unit
cell yielded a total of 33 913 reflections to a maximum θ angle of
25.05° (0.84 Å resolution), of which 6573 were independent (average
redundancy 5.159, completeness = 99.9%, Rint = 4.06%, Rsig = 3.83%)
and 4920 (74.85%) were greater than 2σ(F2). The final cell constants
of a = 8.5544(5) Å, b = 15.2860(8) Å, c = 28.4211(15) Å, β =
91.532(2)°, and volume = 3715.1(4) Å3 are based upon the
refinement of the XYZ-centroids of 9883 reflections above 20 σ(I)
with 4.938° < 2θ < 50.56°. Data were corrected for absorption effects
using the multiscan method (SADABS).14 The ratio of minimum to
maximum apparent transmission was 0.909. The calculated minimum
and maximum transmission coefficients (based on crystal size) are
0.8990 and 0.9870.
5a: HRMS (ESI): calcd for C19H30N2O6Na [M + Na]+: 405.2002,
found: 405.2011.
5b: HRMS (ESI): calcd for C19H30N2O6Na [M + Na]+: 405.2002,
found: 405.2008.
Preparation of Compound 6. To a solution of 2-amino-
anthraquinone (500 mg, 2.24 mmol) in dichloromethane (20 mL)
1,1′-thiocarbonyldi-2(1H)-pyridone (780 mg, 3.36 mmol) was added.
After 30 min the reaction was completed (as monitored by thin-layer
chromatography). The reaction mixture was concentrated under
reduced pressure, and the residue was purified by silica gel column
chromatography (20% hexane in dichloromethane) to give the title
product as a yellow fluffy solid (356 mg, 60% yield). mp 208−209 °C.
HRMS (ESI): calcd for C15H7NO2SNa [M + Na]+: 288.0095,
found: 288.0107.
1H NMR (300 MHz, CDCl3) δ 7.57−7.70 (m, 1H), 7.80−7.90 (m,
2H), 8.12−8.14 (m, 1H), 8.31−8.45 (m, 3H).
13C NMR (75 MHz, CDCl3) δ 124.11, 127.23, 127.43, 129.26,
130.66, 131.44, 133.36, 134.14, 134.34, 134.57, 134.92, 137.49, 181.77,
181.99.
Preparation of Receptor 1. To the solution of amine 5a (428
mg, 1.12 mmol) in 30 mL of dry THF, isothiocyanate 6 (300 mg, 1.13
mmol) was added. After it was stirred overnight at r.t., the reaction
mixture was concentrated and purified by silica gel column
chromatography (2% methanol in chloroform) to give receptor 1 as
an orange solid (456 mg, 63% yield). mp 72−75 °C.
HRMS (ESI): calcd for C34H37N3O8SNa [M + Na]+: 670.2199,
found: 670.2208.
1H NMR (300 MHz, DMSO-d6) δ 3.40−3.80 (m, 24H), 7.15−7.20
(m, 1H), 7.40−7.58 (m, 3H), 7.84−7.98 (m, 2H), 8.08−8.25 (m, 4H),
8.40−8.47 (m, 1H), 10.36 (s, 1H), 10.54 (s, 1H).
13C NMR (75 MHz, DMSO-d6) δ 45.77, 50.01, 68.75, 69.28, 70.38,
70.47, 119.40, 122.29, 123.63, 124.66, 127.16, 127.22, 127.40, 128.34,
128.61, 129.33, 133.56, 133.66, 134.11, 134.76, 135.09, 137.71, 139.39,
145.98, 170.74, 180.01, 181.90, 182.84.
The structure was solved and refined using SHELXTL Software
Package15 using the space group P121/n1, with Z = 4 for the formula
unit, C35.29H40.71ClN3.29NaO12.80S. The final anisotropic full-matrix
least-squares refinement on F2 with 513 variables converged at R1 =
4.03%, for the observed data, and at wR2 = 9.37% for all data. The
goodness-of-fit was 1.052. The largest peak in the final difference
electron density synthesis was 0.272 e−/Å3, and the largest hole was
−0.327 e−/Å3 with an RMS deviation of 0.049 e−/Å3. On the basis of
Anal. Calcd for C34H37N3O8S: C, 63.0; H, 5.8; N, 6.5; S, 5.0%.
Found: C, 62.9; H, 5.7; N, 6.3; S, 5.0%.
Receptor 2. Receptor 2 was synthesized analogously to receptor 1
with the exception that amine 5b was used.
Yellow solid, 60% yield. mp 177−179 °C.
HRMS (ESI): calcd for C34H36N3O8S [M − H]−: 646.2223, found:
646.2227.
B
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Figure 1. Structure of receptors 1 and 2.
the final model, the calculated density was 1.441 g/cm3 and F(000),
1687 e−.
a
Scheme 1. Synthesis of Receptors 1, 2, and 3
The structure contains non-stoichiometric amount of solvent
molecules. Na cation trapped in crown ether is coordinated from
one side by methanol/acetonitrile with refined occupancy ratio equal
to 0.71:0.29. This substitutional disorder is associated with a presence
of less than 10% of water. Hydrogen atoms of this low-occupancy H2O
molecule were not assigned.
The non-hydrogen atoms, except low-occupancy water O atom,
were refined anisotropically. Most of the hydrogen atoms were placed
in calculated positions and refined within the riding model. The
temperature factors of hydrogen atoms were not refined and were set
to be equal to either 1.2 or 1.5 times larger than Ueq of the
corresponding heavy atom. Position sand temperature factors of two
hydrogen atoms in the urea fragment were refined. Position of
hydroxyl H atom in the methanol was refined as well. The atomic
scattering factors were taken from the International Tables.16
RESULTS AND DISCUTIONS
■
Receptor Synthesis. The new salt receptors 1 and 2
(Figure 1) as well as anion receptor 3 were prepared in a simple
approach according to Scheme 1. The reaction of 3-
nitrobenzoyl chloride with 1-aza-18-crown ether in the
presence of triethylamine allowed a cation binding domain to
be introduced in 97% yield. The nitro group in the compound
4a was then reduced using hydrogen and palladium/carbon
catalyst in quantitative yield. The obtained amine 5a was then
reacted with isothiocynate 6 to give receptor 1 in 63% yield. To
avoid very toxic tiophosgene, previously reported isothiocya-
nate 6 was prepared in 60% yield from commercially available
2-aminoanthraquinone using 1,1′-thiocarbonyldi-2(1H)-pyri-
done.7 The regioisomeric ion pair receptor 2 was prepared in
analogous manner starting from 4-nitrobenzoyl chloride.
Finally, treatment of isothiocynate 6 with aniline afforded the
anion receptor 3 in 77% yield.
a
Reagents and conditions: (i) Et3N, 1-aza-18-crown-6, CH2Cl2, 0°C to
r.t., 97% and 95% for 4a and 4b, respectively; (ii) H2, Pd/C, MeOH,
quantitative; (iii) 1,1′-thiocarbonyldi-2(1H)-pyridione, CH2Cl2, r.t.,
60%; (iv) Et3N, THF, r.t., 63% and 60% for 1 and 2, respectively; (v)
aniline, THF, r.t., 77%.
Ultraviolet−Visible Binding Study. A quantitative
evaluation of the anion-, cation-, and salt-binding ability of 1
was investigated by the spectrophotometric titrations method
in CH3CN.8 To rule out the possibility that self-association
might be occurring in the range of concentration under
investigation, dilution studies were first performed, and indeed
no evidence was found of self-association for receptor 1.
Similarly, test experiments with tetrabutylammonium perchlo-
rate ruled out the interaction of receptor 1 with these ions. Job
plot experiments were performed, with the results showing a
1:1 stoichiometry complexation between 1 and the investigated
ions. Then, the affinity of receptors 1 toward selected anions
accompanied by the noncoordinated tetrabutylammonium
cation were studied. The addition of TBA salts of various
anions to 1.24 × 10−4 M solution of 1 caused bathochromic
shifts in the absorption maximum of receptor (Figure 2). The
association constants calculated by nonlinear regression analysis
of the binding isotherms are listed in Table 1. The investigated
Figure 2. Representative UV−vis titration spectra of receptor 1 (upon
gradual addition of tetrabutylammonium chloride). [1] = 1.28 × 10−4
M; optical path length 10 mm.
anions were bound to the receptor moderately, in the order
−
−
NO3 < Br− < NO2 < Cl−. Moreover, upon addition of basic
benzoate and acetate anions, the deprotonation of receptor 1
was observed, together with a color change of the receptor from
C
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regioisomer synthesized from 1-aminoanthraquinone. In the
case of the latter (contrary to the presented receptors 1−3),
intramolecular hydrogen bond formation between the NH of
the thiourea anion binding site and the carbonyl group of the
antraquinone unit highly diminishes the ability of the receptor
to interact with anions (K = 7600 M−1 for receptor 1 vs K =
4300 M−1 for its regioisomer).9
Initially, we presumed that the salt-binding enhancement by
receptor 1 is caused by the simultaneous coordination of
sodium cation to the crown ether and interaction with the
thiourea carbonyl group, a binding mode previously reported
for amino acid-based salt receptors.10 However, the regioiso-
meric reference receptor 2 possessing binding domains in para
position similarly binds sodium salts more strongly than anions
(K = 11 500 M−1 for chloride and K = 25 700 M−1 for chloride
anions in the presence of 1 equiv of Na+), which rules out the
aforementioned binding mode of receptors (Table 2). Thus, we
Table 1. Association Constants (Ka) for Interactions
between Receptors 1 and Selected Anions in the Absence or
a
Presence of 1 equiv of Sodium Perchlorate
1
1+Na+
cooperativity factor
Cl−
10 000
4300
630
230
b
30 900
5600
2700
600
b
3.09
1.30
4.28
2.61
−
−
NO2
Br−
NO3
PhCOO−
AcO−
b
b
a
UV−vis, solvent CH3CN, temperature 293 K, [1] = 1.28 × 10−4 M,
anions added as TBA salts [TBAX] ≈ 6 × 10−3 M; M−1, sodium added
as NaClO4, Errors <10%. Deprotonation.
b
yellow to red. Initially we concluded that receptor 1 was
deprotonated only by the more basic acetate anion because
typical UV−vis spectra for benzoate titration were collected.
1
Table 2. Comparison of Association Constants (Ka) for
Interactions between Receptors 1, 2, and 3 and Chloride
Anions in the Absence or Presence of 1 equiv of Sodium
However, analysis of the H NMR spectra recorded upon
gradual addition of acetate and benzoate anions indicated that
receptor 1 was deprotonated in both cases. Namely, the
addition of carboxylate anions resulted in the disappearance of
signals assigned to thiourea protons (Supporting Information).
In the presence of sodium cations, all moderately bound anions
associated with receptor 1 with remarkably higher stability
constants. The highest cooperativity factor, meaning the
greatest enhancement in anion binding in the presence of
sodium cation relative to tetrabutylammonium salt coordina-
tion, was found for halides. Bromide and chloride anions were
4.28 times and 3.09 times, respectively, more strongly
associated with receptor 1 in the presence of sodium cations.
Since the addition of sodium cations into acetonitrile
solution of receptor 1 caused no change in the UV−vis
absorption band, the selectivity toward cations was studied
using titration with chloride anions in the presence of sodium,
potassium, and ammonium cations. Notably, a significant
improvement in salt binding was observed only in the presence
of sodium cations (K= 10 000 M−1 for chloride anions vs K =
30 900 M−1 for chloride anions in the presence of 1 equiv of
Na+). Both potassium and ammonium chlorides were
associated with receptor 1 even more weakly than tetrabuty-
lammonium chloride (K = 6900 M−1 for chloride anions in the
presence of 1 equiv of K+ and K = 4450 M−1 for chloride anions
a
Perchlorate
L
1
2
3
−
KCl
K[L+Na+]·Cl
10 000
30 900
11 500
25 700
7600
3550
−
a
UV−vis, solvent CH3CN, temperature 293 K, [1] = 1.28 × 10−4 M,
[2] = 1.33 × 10−4 M, [3] = 1.17 × 10−4 M, errors <10%.
concluded that the enhancement of anion binding in the
presence of sodium cations might be attributed to electrostatic
interaction and cation complexation-induced increased acidity
of the thiourea protons of receptors.
1H Nuclear Magnetic Resonance Binding Study. To
1
gain more insight into the ion-pair binding mechanism, H
NMR titrations were performed in acetonitrile solution for
receptor 1. The subsequent addition of sodium perchlorate to
3.2 solution of receptor 1 caused considerable chemical shifts in
1
the H NMR spectrum of the signals corresponding to crown
ether −O−CH2− as well as less pronounced variation of both
thiourea protons. This indicates strong sodium coordination
into the crown ether unit. Analysis of the binding isotherm so
obtained revealed that the receptor coordinated to the sodium
cation strongly, with the high association constant value of
19 950 M−1. However, the addition of potassium or ammonium
hexafluorophosphate to the solution of receptor 1 caused less
+
in the presence of 1 equiv of NH4 ), which evidence the high
selectivity of 1 toward sodium cations.
To establish the role of the cation binding domain in salt
binding, a molecular receptor 3 lacking a crown ether binding
domain and without any substituent on the phenyl ring was
synthesized and tested (Scheme 1). As expected, receptor 3 was
not able to bind sodium salts more strongly than its
tetrabutylammonium counterparts; specifically, sodium chloride
was bound to the receptor more than half as strongly than
tetrabutylammonium chloride (K = 7600 M−1 for chloride and
K = 3550 M−1 for chloride anions in the presence of 1 equiv of
Na+). Interestingly, receptor 3 likewise associated tetrabuty-
lammonium chloride more weakly than receptor 1 (7600 M−1
vs 10 000 M−1). This proves that the crown ether unit
connected to receptor 1 through an amide bond acts not only
as a cation binding site but also diminishes the electron density
in the phenyl ring linked with the anion binding site and as a
consequence reinforces anion binding. Furthermore, the 2-
aminoanthraquinone-based anion receptor 3 is able to create
much stronger complexes with chloride anion than its
1
pronounced changes in the H NMR spectra. The stability
constants for these cations are much lower than for sodium
cations and were calculated to be 125 and 300 M−1,
respectively. Therefore, we concluded that, contrary to the
other investigated cations, strong sodium cation association to
the crown ether units makes this group more electron-
withdrawing and reduces the electron density on the phenyl
ring. Hence, this complexation is responsible for increasing the
acidity of the thiourea protons and thus enhances anion
binding. Indeed, upon addition of sodium cations into receptor
solution, the perturbation in signals assigned to the phenyl ring
connected with the crown ether unit was observed, while the
anthraquinone system remained unchanged. Interestingly, a
slight downfield shift of the thiourea proton attached to the
anthraquinone scaffold was observed; however, the second one
was shifted slightly upfield. The assignment of thiourea protons
1
was done based on H−1H ROESY NMR.
D
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Table 3. 1H NMR Shifts (Δδ) of Selected Protons and Association Constants (Ka) for Interactions of Receptor 1 with Bromide
a
Anions in the Absence or Presence of 1 equiv of Sodium Cations
Ha
Hb
Hc
Hd
He
Hf
K
1
2.69
2.75
2.27
2.42
0.40
0.34
0.21
0.29
0.33
0.31
0.45
0.47
950
1 + 1 equiv of Na+
3710
cooperativity factor
3.90
a
1HNMR, solventCD3CN, temperature 293 K, [1] = 3.03 mM, [TBABr] = 48.4 mM; M−1, errors <10%.
Then 1H NMR anion binding studies were performed. Upon
These anion-induced shifts were higher for NH connected to
the anthraquinone unit and lower for NH attached to the
phenyl ring, indicating the differing participation of thiourea
protons in H-bond formation. Interestingly, the higher anion-
induced shift was observed for the thiourea proton, which was
shifted downfield upon addition of sodium cations. Similarly, all
four aromatic protons neighboring the anion binding site, Hc,
He, Hf, and He, which can form internal C−H···S hydrogen
bonds, also underwent downfield shifts, albeit less distinctly so,
in the range of Δδ = 0.21−0.45. Titration of 1 in the presence
of 1 equiv of sodium cations with bromide anions (added as
TBA salts) induced downfield shifts for all mentioned protons
of receptor 1, similar to those seen in the absence of sodium
cations, although the changes were more drastic in the presence
of a cation. Analyzing the anion complexation-induced shifts of
all mentioned protons of receptor 1 allowed the stability
constants to be determined. Thus, we found that receptor 1
addition of TBABr, considerable downfield shifts in both NH
protons were observed (Figure 3, Table 3), indicating the
formation of strong hydrogen bonds between anions and
receptor 1.
associated with bromide anion moderately (KBr = 950 M−1).
−
However, in the presence of sodium cations the association of
bromide anions was greatly enhanced. Specifically, the bromide
anions were 3.90 times more strongly bound to receptor 1. The
data collected from 1H NMR titrations experiments are
consistent with those obtained from UV−vis titration measure-
ments.
X-ray Measurements. The strong sodium cation binding is
also supported by solid-state X-ray crystallography measure-
ments. Despite making a number of attempts to crystallize
guest complexes of receptor 1, we were unable to obtain
crystals. However, slow diffusion of diethyl ether into an
MeCN/MeOH solution of sodium pretreated reference
receptor 2 enabled us to obtain crystals suitable for X-ray
diffraction analysis. Because receptor 2 possesses the same
binding domains as receptor 1, the [2·NaClO4] complex was
used as a model for further considerations.
Figure 3. 1H NMR titrations of receptor 1 with TBABr in the
presence of 1 equiv of NaClO4. Profiles based on the chemical shift (δ,
ppm) of thiourea and aromatic protons. Open symbols refer to the
titration in the absence of sodium cations; full symbols refer to the
titration in the presence of sodium cations.
In the solid state the sodium cation is located in the 18-aza-6-
crown ether cavity, similarly to the sodium complexes of 15-
crown-5.11 In the [2·NaClO4] complex the sodium cation is
Figure 4. (a) X-ray crystal structure of [2·NaClO4] complex. (b) Hydrogen bonding interactions in [2·Na+] complex (with lattice solvents and
perchlorate anion omitted for clarity).
E
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Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
strongly bonded to five O atoms, with the Na−O distances
ranging from 2.430 to 2.581 Å, while the nitrogen atom is
involved in amide bond formation and does not participate in
sodium complexation. The average Na−O distance is 2.49 Å
and is rather longer than that found for the sodium complexes
of 15-crown-5. This is due to two longer Na−O bonds with the
oxygen atoms located close to the nitrogen atom (2.537 and
2.581 Å, respectively). The sodium cation in the [2·NaClO4]
complex is also coordinated from on site to oxygen atoms of
perchlorate anion and on the opposite site is coordinated by
methanol/acetonitrile with refined occupancy ratio equal to
0.71:0.29. The sodium cation lies almost in the center of the
plane formed by the five O atoms of the crown ether (0.043 Å
above the plane toward the perchlorate anion). Two O atoms
of the crown ether lie below this plane, the other three above.
Moreover in the solid state (in the absence of anions) the
thiourea group interacts through two hydrogen bonds with the
oxygen atom of the amide group (N−H−O distance 2.819 and
2.901 Å) forming head-to-tail dimers (Figure 4).
Electrochemical Measurements. Finally, the electro-
chemical properties of receptor 1 toward selected anions in
the absence and presence of Na+ were studied using cyclic
voltammetry. Receptor 1 shows two consecutive one-electron
reversible waves in acetonitrile solution, corresponding to two
single-electron reductions to give mono- and dianion species.
The cyclic voltammogram obtained for receptor 1 is presented
in Figure 5 as a solid black line. Potentials corresponding to
reduction peaks for receptors 1 are found to be Ep(I) = −1.166
V and Ep(II) = −1.473 V. The potentials of the two peaks
depend on the addition of anions and sodium salts. However,
the potential changes for the first peak are more marked, and
therefore behavior of this peak was used for further analysis.
Figure 5. Cyclic voltammograms recorded for 0.5 mM solution of
receptor 1 (solid black line), after adding 1, 3, and 5 equiv of TBANO2
(gray lines) (A); after adding 1 equiv of NaClO4 (dashed black line)
and then after adding 1, 3, and 5 equiv of TBANO2 (gray lines) (B) in
acetonitrile. The concentration of supporting electrolyte TBAPF6 was
0.1 M, and scan rate was 100 mV s−1.
Upon addition of 1, 3, or 5 equiv of anions (Cl−, Br−, NO2 ,
−
−
NO3 ) the potential of the first peak shifts gradually toward
more negative potentials. Typical voltammograms recorded
−
after adding NO2 are presented in Figure 5A. However, upon
addition of sodium cations the potential of the first peak also
shifts, but this time toward positive potentials. This could
support the conclusion that complexation of sodium cations
into the crown ether ring decreases electron density, which is
perceptible in the antraquinone reporter unit. Then, addition of
anions again gradually shifts the peak potential toward more
negative potential. Typical voltammograms recorded after
Table 4. Changes in Reduction Potentials (mV) of Receptors
1 and 3 after Addition of Various Amounts of Anions and
a
Sodium Salts
Cl−
1 + Na+
Br−
1 + Na+
NO2
NO3
−
−
equiv
1
1
1
1 + Na+
1
1 + Na+
−
adding 1 equiv of Na+ and then 1, 3, or 5 equiv of NO2 are
presented in Figure 5B. Numerical data showing changes in
reduction potentials for other investigated anions are shown in
Table 4.
1
3
5
20
46
62
29
58
79
2
3
14
20
5
23
44
56
b
3
7
b
6
8
6
22
34
Cl−
11
Therefore, the changes in reduction potentials upon addition
of anions to the 1 + 1 equiv of Na+ are much greater than for
the association of receptor 1 with anions in the absence of
sodium cations. Furthermore, in the case of homotopic anion
receptor 3 the addition of chloride anions in the presence of
sodium cations resulted in smaller changes in reduction
potentials relative to chloride anion association. This difference
is a consequence of ion-pair formation out of the receptor, in
the case of the binding event involving the homotopic receptor
3, lacking a crown ether unit.
equiv
2
2 + Na+
3
3 + Na+
1
3
5
20
40
51
28
45
58
16
44
65
8
36
54
a
Anions added as TBA salts, sodium salts added as mixture of TBA
salts and 1 equiv of NaClO4, ΔE = Ep(I) free receptor (or + 1 equiv of Na ) − Ep(I)
+
b
.
The reduction potentials shifts were too small to
anion complex
determine ΔE accurately.
In the case of acetate and benzoate anions, different behavior
was observed. Specifically, upon addition of 1 equiv of
carboxylate anions the potential of the peak was shifted
considerably, and excess of anions added resulted in no further
changes in the cyclic voltammogram. This could suggest strong
complexation of acetate and benzoate toward receptor 1.
However, careful analysis of the response of receptor 1 upon
addition of 0.25, 0.5, and 0.75 equiv of of carboxylate anions
showed that, unlike the other anions investigated, in this case
there is no gradual shifting of the peak but rather a
disappearance of the old one and the formation of a new
F
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Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
peak. This can be attributed to the formation of a new species,
namely, a deprotonated form of receptor 1. Typical voltammo-
grams recorded after adding AcO− are presented in Figure 6.
X-ray crystallographic information on [2·NaClO4].
(CIF)
AUTHOR INFORMATION
Corresponding Author
*E-mail: jarom@chem.uw.edu.pl.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Dedicated to Prof. Janusz Jurczak on the occasion of his 75th
birthday. This work was supported by Grant No. DEC-2013/
09/B/ST5/00988 from the Polish National Science Center.
The X-ray structure was determined in the Advanced Crystal
Engineering Laboratory (aceLAB) at the Chemistry Dept. of
the Univ. of Warsaw by Dr. L. Dobrzycki.
REFERENCES
Figure 6. Cyclic voltammograms recorded for 0.5 mM solution of
receptor 1 (solid black line), after adding 0.25, 0.50, 0.75, and 1 equiv
of TBAAcO (gray lines) in acetonitrile. The concentration of
supporting electrolyte TBAPF6 was 0.1 M, and scan rate was 100
mV s−1.
■
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CONCLUSION
■
In conclusion, we have synthesized simple but effective salt
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ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.inorg-
chem.6b00132.
1H and 13C NMR spectra of compounds 4a, 5a, 6, and
receptors 1, 2, and 3; 1H−1H ROESY of [1·Na+];
1
representative UV−vis and H NMR titration spectra of
receptor 1; dilution curve and Job plot of receptor 1;
UV−vis and NMR binding isotherms, cyclic voltammo-
grams for 2 and 3; crystal data of [2·NaClO4] complex.
(PDF)
G
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Inorganic Chemistry
Article
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