Spectroscopic, structural, and theoretical studies of halide complexes with a urea-based tripodal receptor

Article abstract of DOI:10.1021/ic202747q

A urea-based tripodal receptor L substituted with p-cyanophenyl groups has been studied for halide anions using ¹H NMR spectroscopy, density functional theory (DFT) calculations, and X-ray crystallography. The ¹H NMR titration studies suggest that the receptor forms a 1:1 complex with an anion, showing a binding trend in the order of fluoride > chloride > bromide > iodide. The interaction of a fluoride anion with the receptor was further confirmed by 2D NOESY and ¹⁹F NMR spectroscopy in DMSO-d₆. DFT calculations indicate that the internal halide anion is held by six NH...X interactions with L, showing the highest binding energy for the fluoride complex. Structural characterization of the chloride, bromide, and silicon hexafluoride complexes of [LH⁺] reveals that the anion is externally located via hydrogen bonding interactions. For the bromide or chloride complex, two anions are bridged with two receptors to form a centrosymmetric dimer, while for the silicon hexafluoride complex, the anion is located within a cage formed by six ligands and two water molecules.

Full text of DOI:10.1021/ic202747q

Article
pubs.acs.org/IC
Spectroscopic, Structural, and Theoretical Studies of Halide
Complexes with a Urea-Based Tripodal Receptor
Avijit Pramanik,† Douglas R. Powell,‡ Bryan M. Wong,§ and Md. Alamgir Hossain*,†
†Department of Chemistry and Biochemistry, Jackson State University, Jackson, Mississippi 39212, United States
‡Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019, United States
§Materials Chemistry Department, Sandia National Laboratories, Livermore, California 94551, United States
S
* Supporting Information
ABSTRACT: A urea-based tripodal receptor L substituted
with p-cyanophenyl groups has been studied for halide anions
using 1H NMR spectroscopy, density functional theory (DFT)
calculations, and X-ray crystallography. The 1H NMR titration
studies suggest that the receptor forms a 1:1 complex with an
anion, showing a binding trend in the order of fluoride >
chloride > bromide > iodide. The interaction of a fluoride
anion with the receptor was further confirmed by 2D NOESY
and 19F NMR spectroscopy in DMSO-d6. DFT calculations indicate that the internal halide anion is held by six NH···X
interactions with L, showing the highest binding energy for the fluoride complex. Structural characterization of the chloride,
bromide, and silicon hexafluoride complexes of [LH+] reveals that the anion is externally located via hydrogen bonding
interactions. For the bromide or chloride complex, two anions are bridged with two receptors to form a centrosymmetric dimer,
while for the silicon hexafluoride complex, the anion is located within a cage formed by six ligands and two water molecules.
pyridine framework, which after protonation binds a chloride in
a pentadentate fashion, forming a five-coordinate chloride
INTRODUCTION
■
Anions are ubiquitous in nature and play a key role in chemistry
and biology.1 Because of their widespread importance, anion
recognition with synthetic receptors continues to be an active
area of research in supramolecular chemistry.2,3 Early research
in this area has focused primarily on polyamine-based receptors
that require protonation to bind an anion.4−7 In order to
overcome this limitation, researchers have started using neutral
molecules functionalized with amide,8−11 thioamide,12,13
urea,14−16 thiourea,17,18 pyrrole,19−21 and indole22−25 groups
that can readily form H bonds with an anion regardless of
solution pH. In particular, the electron withdrawing nature of
the oxygen atom in the urea-based molecule can result in the
formation of two hydrogen bonds with an anionic guest,
providing directional binding modes (Scheme 1). For example,
a simple dimethyl urea receptor containing a single urea group
reported by Hamilton et al. was shown to bind an acetate (K =
45 M−1) in DMSO.26 Attaching the urea group to two 4-
nitrophenyl groups, Fabbrizzi et al. synthesized a bis(4-
nitrophenyl) urea receptor which was shown to form a 1:1
complex with a variety of anions, showing a high affinity for
fluoride (K = 2.40 × 107 M−1) in CH3CN.27 Albrecht et al.
reported a quinoline-based receptor containing both amide and
urea groups that was found to complex halides in CHCl3,
showing a high affinity for fluoride (K = 1.44 × 105 M−1).28
Gale et al. obtained a urea-based receptor with attached indole
groups and isolated a crystal with carbonate in which the anion
species was surrounded by two receptors with both indole and
urea NH functional groups.29 Johnson et al. characterized a
dipodal urea based on rigid acetylene groups with a central
complex.30 Martinez-Man
́
ez et al. prepared colorimetric sensors
̃
by attaching 4-nitroazobenzene to an acyclic urea appended to
a dye, showing a complex with atmospheric CO2 in the
presence of fluoride ions. The resulting carbonate complex was
formed due to the deprotonation of the NH groups by fluoride
ions in water.31
A number of synthetic receptors based on tris(2-
aminoethyl)amine (tren) have been reported in the literature,
which are primarily limited to polyamines.32−37 Recently,
several groups have taken advantage of using this framework for
synthesizing urea-based neutral hosts as effective receptors to
complex an anion with multiple H bonds.38−44 For example,
Custelcean et al. reported a tripodal urea substituted with m-
cyanophenyl groups that formed a silver-based MOF in the
presence of Ag2SO4, where a doubly charged sulfate was
encapsulated with twelve hydrogen bonds.38 Wu et al. reported
a multiply coordinated sulfate complex with a tripodal urea
substituted with 3-pyridyl groups.39 Ghosh et al. reported a
pentafluorophenyl-substituted tripodal urea encapsulating a
fluoride anion with six NH bonds.40 Very recently, Gale and co-
workers reported a series of fluorinated tren-based ureas and
thioureas which have been shown to function as anticancer
agents through transmembrane transport mechanism of anions
in vitro.44
Received: December 22, 2011
Published: March 12, 2012
© 2012 American Chemical Society
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Synthesis. L. Tris(2-aminoethyl) amine (300 mg, 2.05
mmol) was added with p-cyanophenyl isocyanate (886 mg, 6.15
mol) in chloroform at room temperature under constant
stirring. The mixture was refluxed for 3 h. The precipitate was
collected by filtration and was washed by chloroform and dried
Scheme 1. Schematic Representation of (i) a Urea Unit and
Its Directional Binding Mode for an Anion, (ii) Urea-Based
Tripodal Receptor (L), and (iii) Electrostatic Potential Map
for L Calculated at the M06-2X/6-31G(d,p) Level of Theory
(red = negative potential, blue = positive potential)
1
to give the neutral host. Yield: 1.07 g, 90%. H NMR (500
MHz, DMSO-d6, TSP): δ 9.14 (s, 3H, Ar−NH), 7.67 (d, J = 8.5
Hz, 6H, ArH), 7.58 (d, J = 8.5 Hz, 6H, ArH), δ 6.39 (m, J1 =
5.5 Hz, J2 = 5.05 Hz, 3H, CH2NH), 3.24 (m, J1 = 6.1 Hz, J2 =
5.95 Hz, J3 = 5.90 Hz, 6H, NHCH2), 2.64 (t, J1 = 6.55 Hz, J2 =
6.45 Hz, 6H, NCH2). 13C NMR (125 MHz, DMSO-d6,): δ
154.9 (CO), 145.4 (Ar−C), 133.6 (Ar−CH), 120.0 (Ar−
CN), 118.0 (Ar−CH), 102.8 (ArC−CN)), 54.0 (NHCH2), 37.9
(NCH2). ESI-MS: m/z (+) 579.63 [M + H]+. Anal. Calcd. for
C30H30N10O3: C, 62.27; H, 5.23; N, 24.21. Found: C, 62.36; H,
5.24; N, 24.22. Crystals suitable for X-ray analysis were grown
in two days from slow evaporation of the acetonitrile solvent at
room temperature.
[HL](Cl), 1. The neutral host L (25 mg) was suspended in MeOH
(10 mL), and a few (approximately five) drops of 40% HCl drops were
added to the mixture. After stirring for 30 min, the clear solution was
kept at room temperature. Prism-shaped crystals suitable for X-ray
analysis were grown from this solution by slow evaporation after one
week. ESI-MS: m/z (+) 616.09 [M + H]+. Anal. Calcd (%) for
C30H31ClN10O3: C, 58.58; H, 5.07; N, 22.77. Found: C, 58.49; H,
5.05; N, 22.73.
[HL](Br), 2. The neutral host L (25 mg) was suspended in MeOH
(10 mL), and a few (approximately five) drops of 49% HF were added
in the mixture. After stirring for 30 min, the clear solution was kept at
room temperature. Block-shaped crystals suitable for X-ray analysis
were grown from this solution by slow evaporation after one week.
ESI-MS: m/z (+) 559.53 [M + H]+. Anal. Calcd (%) for
C30H31BrN10O3: C, 54.63; H, 4.73; N, 21.23. Found: C, 54.69; H,
4.76; N, 21.21.
We have previously reported a tripodal receptor, L, with
three p-cyanophenyl groups as electron-withdrawing substitu-
ents, showing high selectivity for sulfate and hydrogen sulfate
over other oxoanions.45 It was hoped that the introduction of
this group would enhance the acidity of the attached NH
groups, thereby increasing the anion binding ability of the host.
This assumption was further supported by a calculation of the
electrostatic potential surfaces of L at the M06-2X/6-31G(d,p)
level of theory (discussed later), showing the highest electron
density on cyano groups and the most positive potential on the
NH groups (Scheme 1). In addition, the conformational
flexibility with six H-donor groups may allow the binding of a
spherical halide within the ligand’s cavity. We now report the
results of halide binding studies of L in solution, structural
aspects of several complexes, and computational studies. In
particular, we show that the urea-based tripodal receptor has a
significant selectivity for the fluoride anion in DMSO-d6, which
is further confirmed by 2D NOESY experiments.
[HL]2(SiF6)·6.35(H2O), 3. In an attempt to prepare the fluoride salt
of L, silicon hexafluoride salt was obtained. The neutral host L (25
mg) was suspended in MeOH (10 mL), and a few drops of 49% HF
(approximately 5 drops) were added in the mixture. After stirring for
30 min, the clear solution was kept at room temperature. Prism-shaped
crystals suitable for X-ray analysis were grown from this solution by
slow evaporation after three days. Due to an insufficient amount of
crystals obtained, no characterization was carried out for this salt
except X-ray crystallography.
1
NMR Studies. H NMR titration studies were done to determine
the binding constants of L for halides (F−, Cl−, Br−, and I−) in DMSO-
d6 at room temperature. [n-Bu4N]+X− was used as a source of the
anion. Initial concentrations were [ligand]0 = 2 mM, and [anion]0 = 20
mM. Each titration was performed by 13 measurements at room
temperature. The association constant K was calculated by fitting two
NH signals with a 1:1 binding model, using the equation Δδ = ([A]0 +
[L]0 + 1/K − (([A]0 + [L]0 + 1/K)2 − 4[L]0[A]0)1/2)Δδmax/2[L]0
(where L is the ligand and A is the anion).46 The error limit in K was
less than 10%. 19F NMR studies were performed using 20 mM [n-
Bu4N]+F− in DMSO-d6 at 25 °C. 19F NMR spectra were recorded for
the fluoride solution before and after the addition of L (20 mM in
DMSO-d6), while a solution of NaF in D2O in a sealed capillary tube
was used as an external reference.
EXPERIMENTAL SECTION
■
General. All of the chemicals were purchased as reagent grade and
were used without further purification. Nuclear magnetic resonance
(NMR) spectra were recorded on a Varian Unity INOVA 500 FT-
NMR. Chemical shifts for samples were measured in DMSO-d6 and
calibrated against sodium salt of 3-(trimethylsilyl) propionic-2,2,3,3,-d4
acid (TSP) as an external reference in a sealed capillary tube. All NMR
data were processed and analyzed with MestReNova version 6.1.1-
6384. IR spectra were recorded in KBr pellets on a Perkin-Elmer FT-
IR spectrometer. Mass spectral data were obtained in the ESI-MS
positive mode on a FINNIGAN LCQDUO. The melting point was
determined on a Mel-Temp (Electrothermal 120 VAC 50/60 Hz)
melting point apparatus and was uncorrected. Elemental analysis was
carried out by Columbia Analytical Services (Tucson, AZ 85714). All
of the structures reported here were analyzed from the X-ray
laboratory at the University of Oklahoma.
DFT Calculations. In order to quantitatively understand the
unique bonding within the tripodal urea ligand, density functional
theory (DFT) calculations were carried out on each of the three F−,
Cl−, and Br− anions. All quantum chemical calculations were carried
out with the recent M06-2X meta-GGA hybrid functional, which has
been shown to accurately predict the binding energies of ions and
other noncovalent bonding interactions in large molecular sys-
tems.47,48 Molecular geometries (including the empty ligand) were
completely optimized without constraints at the M06-2X/6-31G(d,p)
level of theory, and single-point energies with a very large 6-
311+G(d,p) basis set were carried out in the presence of a polarizable
continuum model (PCM) solvent model to approximate a DMSO
environment (dielectric constant = 46.8).
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Table 1. Crystallographic Data for L; [HL](Cl), 1; [HL](Br), 2; and [HL]2(SiF6)·6.35(H2O), 3
L
1
2
3
chemical formula
M
C30H30N10O3
578.64
C30H31ClN10O3
615.10
C30H31BrN10O3
659.56
C60H74.70F6N20O12.35Si
1415.79
monoclinic
15.4907(14)
11.5343(11)
19.4685(17)
90.00
cryst syst
a/Å
triclinic
monoclinic
13.2509(18)
11.3650(16)
19.471(2)
90.00
monoclinic
13.2935(19)
11.3515(17)
19.928(3)
90.00
8.7312(11)
12.8400(17)
13.6820(18)
91.989(3)
107.888(2)
100.753(2)
1427.1(3)
100(2)
b/Å
c/Å
α/deg
β/deg
97.470(8)
90.00
97.895(3)
90.00
96.061(2)
90.00
γ/deg
V/Å3
2907.4(6)
100(2)
2978.7(8)
100(2)
3459.1(5)
100(2)
T/K
space group
P1
̅
P21/n
P21/n
P21/n
Z
2
4
4
2
μ/mm−1
reflns measured
indept reflns
Rint
0.092
16034
7004
0.184
1.431
0.124
35737
28725
35178
7232
6091
8552
0.0320
0.0495
0.1166
0.1273
1.003
0.0721
0.1087
0.0650
a
R1 (I > 2σ(I))
0.0519
0.0540
0.0600
wR(F2) values (I > 2σ(I))
0.1083
0.1037
0.1408
b
wR2 (all data)
0.1202
0.1150
0.1581
goodness of fit
1.010
1.012
1.003
a
b
2
2
R1 = ∑ ||Fo| − |Fc||/∑ |Fo|. wR2 = {∑[w(Fo − Fc2)2]/∑ [w(Fo )2]}1/2
.
Table 2. Selected Hydrogen Bonding Parameters (Å, degrees) for the Ligand and Different Anion Complexes
L
1
D−H···A
D···A
∠D−H···A
D−H···A
D···A
∠D−H···A
N(4)−H(4)···O(20)
N(7)−H(7)···O(20)
N(18)−H(18)···O(34)
N(21)−H(21)···O(34)
2.9397(18)
2.8849(17)
2.8925(17)
3.0807(18)
2.9315(18)
2.9315(18)
154.0(17)
153.2(16)
160.6(16)
149.8(16)
150.2(16)
150.2(16)
N(1)−H(1)···O(34)
N(4)−H(4)···Cl(1)
N(7)−H(7)···Cl(1)
N(18)−H(18)···O(6)
N(32)−H(32)···O(20)
2.744(2)
156.3(19)
157.3(18)
162.0(18)
176(2)
3.2776(18)
3.1802(18)
2.912(2)
a
a
b
c
N(32)−H(32)···O(6)
3.024(2)
127(2)
b
d
N(32)−H(32)···O(6)
N(32)−H(32)···Cl(1)
N(35)−H(35)···Cl(1)
3.5679(18)
3.2016(18)
135.4(19)
175(2)
d
2
3
D−H···A
D···A
∠D−H···A
D−H···A
D···A
D−H···A
N(1)−H(1)···O(20)
N(1)−H(1)···N(32)
N(4)−H(4)···Br(1)
N(7)−H(7)···Br(1)
N(18)−H(18)···Br(1)
N(32)−H(32)···O(6)
2.755(4)
3.056(4)
3.405(3)
3.335(3)
3.645(3)
2.919(4)
153(3)
106(2)
157(3)
166(3)
149(3)
178(4)
N(1)−H(1)···O(20)
N(1)−H(1)···O(6)
N(4)−H(4)···F(1)
N(4)−H(4)···F(2)
N(7)−H(7)···F(2)
N(18)−H(18)···F(2)
N(18)−H(18)···F(3)
N(21)−H(21)···F(1)
2.834(2)
3.028(2)
2.953(2)
3.266(2)
2.833(2)
2.978(2)
3.349(3)
2.823(2)
143(2)
122.7(19)
159(2)
142(2)
171(2)
156(3)
146(2)
173(2)
f
e
g
h
i
h
(1S)−H(1SB)···F(3)
2.842(2)
156(3)
a
b
c
d
e
f
g
1 − x, −y + 1, −z. 2 − x + 1, −y + 1, −z + 1. 1 −x + 1, −y, −z. 2 −x + 1, −y + 1, −z. 1 − x + 1, −y + 1, −z + 1. 1 − x + 1, −y, −z + 1. 2 − x +
h
i
1, −y + 1, −z + 1. x, y + 1, z. −x + 3/2, y − 1/2, −z + 3/2.
X-Ray Crystallography. The crystallographic data and details of
data collection for the free ligand L and the anion complexes 1−3 are
given in Table 1. Intensity data for all four samples were collected
using a diffractometer with a Bruker APEX CCD area detector and
graphite monochromated Mo Kα radiation (λ = 0.71073 Å).49,50 The
difference map, and their positions were refined independently. Non-
hydrogen atoms were refined with anisotropic displacement
parameters. Hydrogen atom displacement parameters were set to 1.2
times the isotropic equivalent displacement parameters of the bonded
atoms. Hydrogen-bonding interactions are shown in Table 2.
samples were cooled to 100(2) K. The triclinic space group P1 in L
̅
was determined by statistical tests and verified by subsequent
refinement, while the monoclinic space group P21/n in 1, 2, and 3
was determined by systematic absences and statistical tests with
verification by subsequent refinement. The structure was solved by
direct methods and refined by full-matrix least-squares methods on
F2.51 The positions of hydrogens bonded to carbons were refined by a
riding model. Hydrogens bonded to nitrogens were located on a
RESULTS AND DISCUSSION
■
Synthesis. The synthesis of L was previously reported by
our group and obtained as a pure product in high yield. A
similar approach was also employed to synthesize related urea-
based hosts by other groups.38−40 Attempts to prepare
complexes of neutral receptors with tetrabutyl ammonium
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1
Figure 1. Partial H NMR spectra of L (2 mM) in the absence and
presence of an anion showing two NH peaks in DMSO-d6. An
Figure 3. Partial 19F NMR spectra of [n-Bu4N]+F− in DMSO-d6 at
room temperature, showing the downfield shift of F− resonance upon
the gradual addition of L. (a) Free [n-Bu4N]+F− (δF = −105.2 ppm),
(b) [n-Bu4N]+F− + 0.25 equiv of L (δF = −102.5 ppm), (c) [n-
Bu4N]+F− + 0.50 equiv of L (δF = −96.4 ppm), and (d) [n-Bu4N]+F−
+ 1.0 equiv of L (δF = −90.1 ppm).
equivalent amount of [n-Bu4N]+X− was added to the ligand solution.
halides were unsuccessful; therefore, L was converted to
chloride and bromide salts by reacting with corresponding acids
in methanol. The addition of hydrofluoric acid to the
methanolic solution of L led to the formation of silicon
hexafluoride (SiF62−) salts due to the corrosion effect of HF to
the glass vial.34 The compound was fairly stable under acidic
conditions, allowing for the protonation at the tertiary amine.
All of the salts were characterized by single crystal structure
analysis.
Scheme 2. Proposed Binding Mechanism of L for an Anion
in Solution
NMR Titrations. The binding properties of L for halides
were examined by 1H NMR titration studies using [n-
Bu4N]+X− (X− = F−, Cl−, Br−, and I−) in DMSO-d6. Figure
1 shows the 1H NMR spectra of the ligand before and after the
addition of one equivalent halide ion. In the 1H NMR of free L,
two NH protons in a different chemical environment appear at
9.14 (H2) and 6.39 (H1) ppm. The addition of F− to L
resulted in a significant downfield shift of both NH signals (Δδ
= 1.78 ppm for H2 and Δδ = 0.86 ppm for H1), suggesting an
interaction of the anion with NH groups. A similar trend,
although to a lesser extent, was observed for those protons
upon the addition of Cl−. However, in the case of Br− or I−,
there was little change in the chemical shifts. Figure 2a shows
10 equivalents), displaying a systematic shift change in the NH
signals. The changes in the chemical shift of NH peaks of the
ligand were recorded with an increasing amount of halide
solution at room temperature, giving the best fit for a 1:1
binding model (Figure 2b). The 1:1 stoichiometry of the halide
complex in solution was further verified by a Job plot displaying
1
the stacking of H NMR titration spectra obtained from the
experiments with portion-wise additions of chloride ions (0 to
1
1
Figure 2. (a) Partial H NMR titration of L (2 mM) with an increasing addition of [n-Bu4N]+Cl− (20 mM) in DMSO-d6. (b) H NMR titration
curves of L with [n-Bu4N]+Cl− in DMSO-d6 showing the net changes in the chemical shifts of NH (H1 = CH2NHCO and H2 = CONHAr).
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Figure 4. 2D NOESY NMR spectra of (a) free L and L in the presence of one equivalent of (b) fluoride, (c) bromide, and (d) iodide anions in
DMSO-d6 at room temperature.
Table 3. Binding Constants (log K) of Tripodal tris-Urea
Receptor (L) with Halides in DMSO-d6
former peak is assigned to the reference fluoride ion solvated
with D2O, while the latter is due to the fluoride ion of [n-
Bu4N]+F− in DMSO-d6. As clearly shown in Figure 3b−d, the
addition of L (20 mM) to the fluoride solution resulted in a
gradual downfield shift of the free fluoride resonance, indicating
the hydrogen bonding interactions of the fluoride ion with the
NH groups of L. In particular, we observed a significant
downfield shift of about 15 ppm after the addition of one
equivalent of L. A similar trend in downfield shifts was
previously reported for fluoride binding with an amide-based
cryptand receptor.52
In order to characterize the solution structure of the
complexes, 2D NOESY NMR experiments were carried out
in DMSO-d6 at room temperature. In the 2D NOESY NMR,
the free ligand showed two strong NOE contacts between
H2···H3 and H1···H2 (Scheme 2 and Figure 4), which could be
due to the fact that the aromatic plane connected to a urea unit
is coplanar with the NH group. Such an assumption is further
supported by the single crystal structure analysis of the free
ligand (discussed later). Upon the addition of one equivalent of
fluoride ions, all of the NOE contacts disappeared, indicating a
conformational change of L due to the encapsulation of the
anion. Indeed, the ligand showed high affinity for fluoride (log
K = 4.51) in DMSO-d6, as discussed in the previous section.
The encapsulation was further confirmed by molecular
modeling studies performed in the same solvent environment
anion
log K
fluoride
chloride
bromide
iodide
4.51
3.09
1.71
1.01
a maximum at an equimolar ratio of the anion and L (Figure
S6). The binding constants of L were determined from a
nonlinear regression analysis of NH shift changes, showing a
binding affinity in the order of F− > Cl− > Br− > I−. Specially,
the ligand L showed a strong affinity for the fluoride anion (log
K = 4.51) compared to the chloride anion (log K = 3.09). This
data suggest that the binding is largely dominated by the
relative electronegativity and size of the anions. The highest
binding for F− could be the result of strong electrostatic
interactions of this anion with the acidic NH of the host. The
observed binding constant for fluoride is higher than that
reported in a related host (log K = 4.06).40
19F NMR spectroscopy was also used to identify the chemical
environment of the fluoride in the complex. Figure 3a shows
the 19F NMR spectrum showing two peaks at −122.5 and
−105.2 ppm for free [n-Bu4N]+F− (20 mM) in the presence of
a NaF reference used in a sealed capillary tube in D2O. The
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Figure 5. Optimized structures: (a) perspective view and (b) space filling model of the fluoride complex of L and (c) perspective view and (d) space
filling model of the chloride complex of L.
Table 4. Selected Hydrogen Bonding Parameters (A, deg) for the Halide Complexes in Their Optimized Strictures
[L(F)]−
[L(Cl)]−
[L(Br)]−
D−H···A
D···A
∠D−H···A
D···A
∠D−H···A
D···A
∠D−H···A
N(54)−H···X
N(50)−H···X
N(68)−H···X
N(9)−H···X
N(27)−H···X
N(31)−H···X
2.691
2.802
2.817
2.764
2.907
2.689
152.98
148.94
151.74
151.80
146.36
160.78
3.212
3.465
3.553
3.220
3.486
3.228
160.87
150.48
148.70
160.80
149.90
162.76
3.318
3.613
3.589
3.334
3.525
3.329
161.26
151.15
151.53
164.96
154.05
158.47
(discussed later). Similar conformational changes were
previously reported by Werner and Schneider in the optimized
structure of the chloride complex of a tren-based urea ligand.53
The addition of one equivalent of chloride led to the
disappearance of both NOE contacts (H2···H3 and H1···H2)
in the 2D NOESY NMR spectra. However, the addition of
bromide or iodide apparently did not affect the NOE contacts
in the ligand, which could be due to the very weak interaction
for this anion, as also supported by NMR titration data (Table
3). This observation further supports the formation of an
encapsulated complex of L with fluoride or chloride ions in
solution.
DFT Calculations. The binding properties were also
evaluated by DFT calculations for the free ligand and its halide
complexes (except iodide, where the 6-311+G(d,p) basis set is
not available) using a PCM model in a DMSO environment
(dielectric constant = 46.8). In order to correlate binding
strengths, the stabilization energy for each structure was
calculated as Es = E(ligand) + E(anion) − E(ligand + anion),
and the binding energies for fluoride, chloride, and bromide
complexes were found to be 32.87, 12.90, and 8.49 kcal/mol,
respectively. These values correlate with the data of binding
constants (Table 3), showing the highest binding affinity for
fluoride. Figure 5 shows the optimized geometries of the
fluoride and chloride anions bound to the neutral ligand. From
the DFT-optimized geometries, we found that although six
hydrogen bonds were formed with the individual anion, each of
the conformations showed very distinct binding energies and
configurations. Specifically, for the fluoride complex, the three
arms were twisted, and the anion was tightly bound inside the
cavity, with NH···F bond distances of 2.689−2.907 Å (Figure
5a). The coordination patterns and bond distances are
comparable with the structure of the fluoride complex with a
pentafluorophenyl-substituted tripodal urea (NH···F =
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Figure 6. ORTEP drawing of (a) free L and (b) its dimer, with thermal ellipsoids at the 50% probability level (hydrogen atoms on carbons are
omitted for clarity); (c) space filling view of dimeric L.
Figure 7. ORTEP drawing of (a) [HL](Cl) and (b) its dimer, with thermal ellipsoids at the 50% probability level (hydrogen atoms on carbons are
omitted for clarity); (c) space filling view of dimeric [HL](Cl); (d) lattice structure of [HL](Cl) viewed along the along c axis.
2.700(3)−2.884(3) Å) reported by Ghosh et al.40 As shown in
Table 4, the average bond NH···X distances in the optimized
geometries are 2.78, 3.36, and 3.45 Å for the fluoride, chloride,
and bromide complexes, respectively. The NH···X distances in
the optimized structures of [L(Cl)] and [L(Br)] are also close
to the corresponding values obtained from the crystal structures
ranging from 3.1802(18) to 3.5679(18) Å for [HL](Cl) and
3.335(3) to 3.645(3) Å for [HL](Br). In particular, we
obtained a considerably high binding energy for the fluoride
complex compared to the chloride or bromide complex, which
could be due to the high electron density of the fluoride anion,
making it a stronger H-bond acceptor. In the case of the
chloride or bromide complex, each was shown to form an
almost perfect C3 symmetric complex (for the chloride
complex, see Figure 5b), although the bromide anion was
loosely held due its larger size and lower charge density. This
observation also agrees with the NOESY results, showing the
disappearance of certain NOE contacts for the fluoride complex
(Figure 4b).
Crystal Structure Analysis. The free ligand L crystallizes
in the triclinic P1 space group. The structural analysis of L
̅
shows that it forms a pseudocavity with three arms suitable for
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Figure 8. ORTEP drawing of (a) [HL](Br) and (b) its dimer, with thermal ellipsoids at the 50% probability level (hydrogen atoms on carbons are
omitted for clarity); (c) space filling view of dimeric [HL](Br); (d) lattice structure of [HL](Br) viewed along the along c axis.
hosting an anion (Figure 6a). The cavity possesses an
approximate C3 symmetry axis passing through the tertiary N
atom. Two aromatic units connected to N21 and N35 are
involved in CH···π interactions with a centroid···centroid
distance of 3.652 Å, with two nitrogens N18 and N32 (3.715
Å) in close proximity. Similar interactions were reported before
for a thiophene-based tripodal amine.54 Each urea unit has a
usual anti−anti conformation with respect to NH and the
carbonyl O. The aromatic planes connected to the urea units
are almost coplanar with the NH groups, as indicated by
torsion angles close to 180°. Two NH groups (N4 and N7) in
one arm form two strong intramolecular hydrogen bonds with
one carbonyl oxygen (O20) of another arm. The H-bond
distances are N4···O20 = 2.9397(18) and N7···O20 =
2.8849(17) Å. The molecule forms a centrosymmetric dimer
from the interactions of four intermolecular H-bonds (Figure
6b). As shown in Figure 6c, two units in the dimer are
antiparallel to each other.
The chloride salt of the ligand prepared from the reaction of
L with HCl in ethanol crystallizes as [HL·(Cl)] in the
monoclinic space group P21/n. The tertiary amine is
protonated as expected, and the charge is balanced by one
chloride ion. The proton on the tertiary amine (N1) points
inside the tripodal cavity and is held by a strong H-bond with
one endo-oriented carbonyl oxygen (O34) of a urea group,
with a distance of N···O = 2.744(2) Å. Another intermolecular
hydrogen bonding interaction is observed between the N18 of
one urea and the O6 of another urea with a N···O distance of
2.912(2) Å. Therefore, the cavity is apparently not favorable for
accommodating a chloride in the solid state (Figure 7a). As a
result, the anion remains outside the cavity bonded to one urea
unit with two strong hydrogen bonds (N4···Cl = 3.2776(18)
and N7···Cl = 3.1802(18) Å). This chloride is further
coordinated with a neighboring tren via one strong H-bond
(N35···Cl = 3.2016(18) Å) and one relatively weak H-bond
(N32···Cl = 3.5679(18) Å), resulting in the formation of a
centrosymmetric dimer (Figure 7b and c). Therefore, the
chloride ion is coordinated with a total of four bonds in a
tetragonal pyramidal fashion where the anion is located on the
vertex of pyramid. Hydrogen bonding interactions with the
coordinating chloride ion are shown in Figure 7b. In the crystal,
all NH groups except N21 are involved as H-bond donors
either for the chloride or carbonyl oxygen. As viewed in the
packing diagram along the c axis (Figure 7d), the molecules are
assembled to generate a rod-like structure through NH···Cl
interactions (along the b axes) and several short contacts
between CN (cyano) and CH (aliphatic) groups (along the a
axes).
The structural aspects of the bromide complex of receptor L
are strikingly similar to those of the chloride complex. As
shown in Figure 8a, the host binds a single bromide outside the
cavity. The tertiary amine is found to be protonated, which
points inside the cavity, making a hydrogen bond with one
carbonyl oxygen (N1···O20 = 2.755(4) Å). The bromide is
bonded to both NH groups of the single urea unit (N4···Br =
3.405(3) and N7···Br = 3.335(3) Å). Each urea unit with
respect to the NH and carbonyl O is essentially planar. Two
NH groups (N32 and N35) from a single urea unit are directed
toward the cavity, while the remaining four NH groups are
directed outside the cavity, serving as H-bond donors for
externally located bromide ions in a lattice. The details of the
hydrogen bonding interactions are listed in Table 2. As shown
in Figure 8b and c, two antiparallel tripodal units are paired via
two anions from opposite sites to form a dimer. Figure 8d
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SiF62− through F atoms with L and water. The X-ray analysis of
this complex suggests that the salt crystallizes as
[HL]2(SiF6)·6.35(H2O) in the monoclinic space group P21/n.
2−
One water molecule that is directly bonded with SiF6 was
ordered. Other water molecules were disordered and were
modeled only with isotropic oxygen atoms.
The asymmetric unit contains two tripodal ureas where each
urea is protonated at the terminal nitrogen. Therefore, the total
charges are balanced by one dinegatively charged hexafluor-
osilicate ion. The intramolecular hydrogen bonding interactions
are different than those observed in the chloride or bromide
complex. In this case, the proton is internally bonded with two
carbonyl O atoms with N···O distances of 2.834(2) and
3.028(2) Å, in contrast to the one carbonyl O atom in complex
2−
1 or 2. The coordination environment of the SiF6 is quite
different than that observed in the chloride or bromide
complex. In an asymmetric unit, the anion is held between two
parallel tren units and one water molecule contributing six H-
bonds (five NH···F bonds with urea groups and one OH···F
bond with a water molecule). The ORTEP view of the crystal
structure is depicted in Figure 9a. Tasker et al. reported a
2−
complex of PtCl6 with two protonated tripodal tris-ureas
substituted with butyl groups, showing the participation of two
arms from each receptor to form a sandwich type complex.41
However, in our case, the anion is H-bonded with two arms
from one receptor and one arm from other receptor.
As listed in Table 2, the NH···F bond distances are in the
range from 2.823 to 3.349 Å. The complete coordination
environment of SiF62− is shown in Figure 9b, where the anion is
held by a total of 12 H bonds and entrapped within a hole
generated by six ligands and two water molecules (Figure 10).
In the structure, the anion sits on a crystallographic center of
symmetry. Among the six ligands, four are directly bonded to
the central anion, while the remaining two are connected to the
anion through water molecules.
Figure 9. (a) ORTEP drawing of [HL]2(SiF6) with thermal ellipsoids
at the 50% probability level (hydrogen atoms on carbons are omitted
for clarity); (b) coordination environment of SiF62− showing a total of
12 H-bonds.
CONCLUSIONS
■
We have presented a comprehensive study of a urea-based
tripodal receptor for spherical halide ions using both
experimental and theoretical techniques. In particular, the
receptor was shown to bind a fluoride ion strongly in solution
compared to the other halide ions. The experimental
observations from solution studies are clearly correlated with
predictive methods from DFT calculations, indicating the
formation of an encapsulated complex with hydrogen bond
donors from NH groups. The binding constants in the order of
fluoride > chloride > bromide > iodide suggest that the binding
is primarily dominated by the relative basicity of halides, which
are also in line with the Hofmeister effect.55 An important
aspect of this study is the use of 2D NOESY spectroscopic
techniques to characterize the solution structures. Additionally,
19F NMR spectroscopy has been used to probe the chemical
environment of fluoride in solution. Structural characterization
of the chloride and bromide complexes grown in an acidic
medium suggests that the one halide ion is externally bonded
with two receptors with four NH bonds in both cases, where
the tertiary nitrogen is protonated and points toward the cavity.
The obvious discrepancy in solution and solid-state results
could be due to the proton on the tertiary nitrogen, preventing
the encapsulation of an anion in the cavity. Interestingly, the
protonated receptors are assembled with water molecules to
form a perfect cage to encapsulate a silicon hexafluoride anion.
Since the report on selective neutral receptors is still in its
Figure 10. Space filling views of hexafluorosilicate complex of L,
showing (a) a hole generated by six ligands and two water molecules
2−
and (b) an encapsulated SiF6
.
shows the molecules are also packed with hydrogen bonding
interactions and CN···CH short contacts to form a rod-like
structure, in a similar fashion observed in the chloride complex.
In an attempt to prepare the fluoride complex of L,
hexafluorosilicate salt 3 was obtained from reaction of the
host in methanol with HF acid in a glass vial. Obviously, the
source of hexafluorosilicate in the system is due to the reaction
of HF with the glass. The structure of this complex is included
in this paper because of the interesting bonding aspects of
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(20) Custelcean, R.; Delmau, L. H.; Moyer, B. A.; Sessler, J. L.; Cho,
W.-S.; Gross, D.; Bates, G. W.; Brooks, S. J.; Light, M. E.; Gale, P. A.
Angew. Chem., Int. Ed. 2005, 44, 2537−2542.
infancy, the present solution and solid-state findings coupled
with theoretical results further expand the understanding of
binding mechanisms in host−guest complexes.
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Schmidtchen, F. P.; Bates, G. W.; Light, M. E.; Gale., P. A. J. Am.
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ASSOCIATED CONTENT
■
S
* Supporting Information
(22) Bates, G. W.; Triyanti, L. M. E.; Albrecht, M.; Gale, P. A. J. Org.
Chem. 2007, 72, 8921−8927.
Crystallographic data in CIF format, NMR and mass spectra,
Job’s plot, optimized structures, and Cartesian coordinates for
all optimized structures in PDF formats. This material is
available free of charge via the Internet at http://pubs.acs.org.
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Int. Ed. 2005, 44, 7926−7929.
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AUTHOR INFORMATION
■
Corresponding Author
*E-mail: alamgir.hossain@jsums.edu.
Notes
(27) Boiocchi, M.; Del Boca, L.; Esteban-Gomez, D.; Fabbrizzi, L.;
Licchelli, M.; Monzani, E. J. Am. Chem. Soc. 2004, 126, 16507−16514.
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2850−2858.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The National Science Foundation is acknowledged for a
CAREER award (CHE-1056927) to M.A.H. This work was
supported by the National Institutes of Health
(G12RR013459). The 500 NMR instrument used for this
work was funded by the National Science Foundation (CHE-
0821357). The authors thank the National Science Foundation
(CHE-0130835) and the University of Oklahoma for funds to
acquire the diffractometer used in this work.
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