Aryl C-H...Cl- hydrogen bonding in a fluorescent anion sensor

Article abstract of DOI:10.1039/c3cc44574g

A new phenyl-acetylene receptor containing a carbonaceous hydrogen bond donor activates anion binding in conjunction with two stabilizing ureas. The unusual CH...Cl^- hydrogen bond is apparent in solution by large ¹H NMR chemical shifts and by a short, linear contact in the solid state.

Full text of DOI:10.1039/c3cc44574g

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Aryl C–HÁ Á ÁClÀ hydrogen bonding in a fluorescent
anion sensor†
Cite this: Chem. Commun., 2013,
49, 7240
Blakely W. Tresca,a Lev N. Zakharov,b Calden N. Carroll,a Darren W. Johnson*a and
Michael M. Haley*a
Received 18th June 2013,
Accepted 4th July 2013
DOI: 10.1039/c3cc44574g
www.rsc.org/chemcomm
A new phenyl-acetylene receptor containing a carbonaceous hydrogen
Aryl groups are used as the rigid linkers in supramolecular
bond donor activates anion binding in conjunction with two stabilizing hosts to provide the desired anion receptor geometry. As a
ureas. The unusual CHÁÁÁClÀ hydrogen bond is apparent in solution by result, phenyl protons are a frequent feature in anion binding
large 1H NMR chemical shifts and by a short, linear contact in the pockets.1 Despite their ubiquity, aryl protons play only a small role
solid state.
in the anion binding of most hosts. Contrary to this, calculations
suggest phenyl protons can bind anions with association energies
Numerous supramolecular hosts for anionic guests have been devel- (DG) approaching À9.0 kcal molÀ1 and volumes of crystallographic
oped, including polymers, macrocycles and cryptands.1 Neutral hosts data exist for the general C–HÁÁÁanion interaction.9,13 Recent
frequently combine a complementary geometry and strong hydrogen solution studies have demonstrated the action of C–H hydrogen
bond donors to selectively bind anionic guests.2 A range of hydrogen bonds in supramolecular hosts, yet crystal structures of these
bond donors that exhibit drastically different pKas are found in complexes are still rare.14
supramolecular hosts. Some examples are amides (pKDa MSO E 23–25),
2,6-Bis(2-anilinoethynyl)pyridine (1, Fig. 1) is an easily functiona-
sulfonamides (pKaDMSO E 13–18), phenols (pKDa MSO E 12–20), pyr- lized fluorescent core. Addition of sulfonamides or ureas (e.g., 2) has
roles (pKDa MSO E 23.0) and ureas (pKDa MSO E 20–27).3 These examples illustrated the versatility of this scaffold for the construction of
of hydrogen bond donors all rely on protic N- or O-groups. Highly fluorescent sensors.15 Judicious modification of the substituents
electronegative elements are favored, but are not the only hydrogen allows control of the fluorescent and coordinating properties.16
bond donors extant. Of the donors employed in molecular sensors, Previous work in our labs has demonstrated the increased anion
À
Á
the phenyl C–H pKaH O ꢀ 37 3b donor is relatively underappreciated
by supramolecular chemists.
2
binding ability by the pyridine-protonated receptors (3), showing an
almost two order of magnitude increase in anion binding.17 The
greater anion binding ability of the pyridinium host is limited by its
pKa. While the exact pKa of 3 is not known, the pKas for a series of
similar ethynylpyridines have been measured in acetonitrile; the
electron-withdrawing alkynes shift the pKa of 2,6-bis(ethynyl)-
pyridinium to 8.918 from 12.5 for pyridinium (MeCN).19 This
complicates any attempts to apply a pyridinium-based anion sensor
in an environment such as cells where a low pH cannot be
maintained.18b Replacement of the pyridine with a phenyl moiety
The C–H donor was recognized early on by molecular biologists
as an important component in the secondary structures of bio-
molecules.4,5 Carbonaceous hydrogen bond donors have experienced
a renaissance in recent years with the introduction of new functional
groups, including imidazolium,6 triazole,7 diketopropylene–BF2,8
and benzene.9 The 1,2,3-triazole functionality is a promising anion
binding moiety in neutral receptors,10 since the C–H hydrogen bond
donor is activated by a strong dipole oriented through the nitrogen
atoms.11 As previously observed in other selective hosts, the anion
binding ability of 1,2,3-triazoles is optimized when the receptor is
preorganized in an appropriately sized macrocycle.12
a Department of Chemistry & Biochemistry and the Materials Science Institute,
University of Oregon, Eugene, OR 97403-1253, USA. E-mail: dwj@uoregon.edu,
haley@uoregon.edu; Fax: +1-541-346-0487; Tel: +1-541-346-0456
b Center for Advanced Materials Characterization in Oregon (CAMCOR),
University of Oregon, Eugene, OR 97403-1443, USA
† Electronic supplementary information (ESI) available: Experimental details,
spectroscopic data and X-ray analysis of receptors and titration experiments.
CCDC 929532. For ESI and crystallographic data in CIF or other electronic format
see DOI: 10.1039/c3cc44574g
Fig. 1 Structures of 2,6-bis(2-anilinoethynyl)arene cores 1 and 4 and anion
receptors 2, 3 and 5.
c
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Table 1 Anion association constants (Ka) obtained by fitting titration data using
in the ethynyl core (e.g., 4, 5) will maintain the same geometry, while
altering the electronic and anion binding properties. The phenyl
C–H hydrogen bond offers an opportunity to expand the working
conditions of this sensor and explore the nature of C–H hydrogen
bonds. Herein, we introduce an aryl hydrogen bond donor in place
of the pyridine–pyridinium moiety and report the anion binding
characteristics of this new receptor.
MatLab for 1H NMR data or Hyperquad for UV-Vis dataa
Host
ClÀ/MÀ1
ClÀ DG/kcal molÀ1
BrÀ/MÀ1
IÀ/MÀ1
2
5
3
700b
6700c
À3.88
À5.21
À6.28
—
—
1600b
—
150b
—
40 700c
a
Anions added as tetrabutylammonium salts in water-saturated CHCl3
Phenyl core 4 was obtained by deprotection and subsequent
Sonogashira cross-coupling of ethynylaniline 6 with 1,3-diiodo-
benzene in 47% yield (Scheme 1). Reaction of 4with 4-methoxyphenyl
isocyanate gave bisurea receptor 5 in 94% yield. The anion binding
properties of 5were analyzed using 1H NMR and UV-Vis spectroscopy.
Titrations were performed in water-saturated chloroform with anions
added as tetra-n-butylammonium (TBA) salts. A representative
1H NMR titration experiment with 5 and ClÀ is shown in Fig. 2.
The Dd of urea proton Hg was fit using non-linear regression in
MatLab to determine association constants (Ka).20 A 1:1 host:guest
binding model was used to fit the data as this agrees with previous
binding studies on similar systems.17 In addition, the model is
supported by UV-Vis spectroscopic evidence and solid-state struc-
tures. Association constants for 5 and comparison with data for
structurally similar hosts 2 and 3 are reported in Table 1.
or CDCl3 at 298 K. Error is ca. Æ10% and the values represent an
b
average of three titrations. Titrations performed using 1H NMR.
c
Titrations performed using UV-Vis.
from 700 MÀ1 to 40 700 MÀ1 for 3ÁClÀ.17 The difference in Ka
between 2 and 3 can be separated into three influencing factors:
(1) the repulsive effect of the nitrogen lone pair on 2, (2) the
additional hydrogen bond in 3, and (3) the electrostatic interaction
of ClÀ with 3. For the three hosts, receptor 2 has the lowest energy
interaction due to the repulsion between the pyridine lone pair. The
inclusion of an aryl C–H hydrogen bond donor in 5 increases the Ka
by an order of magnitude for ClÀ (Table 1). The difference in energy
(DDG = DG 2ÁClÀ À DG 5ÁClÀ) is 1.33 kcal molÀ1. This DDG is
very close to the value (1.44 kcal molÀ1) reported by Sessler
et al. for strapped pyrroles containing benzene or furan.21 The
additional electrostatic attraction in protonated receptor 3 leads to
1.07 kcal molÀ1 added stabilization (DDG). This value is perhaps
smaller due to competition from the trifluoroacetate counter ion.
2-D HSQC and ROSY NMR spectroscopy were used to assign the
urea and aryl peaks in the proton NMR spectrum of 5 (see Fig. S20–
S22 in the ESI†). The urea protons (Hh and Hg) shift downfield upon
addition of ClÀ. A close examination of the aryl peak Hc reveals a
large downfield shift, Dd > 2 ppm. The magnitude of Dd suggests a
strong aryl hydrogen bond, but may also be influenced by structural
changes induced by anion binding. The other aromatic peaks shift
very little or slightly upfield likely as a result of weak CH–p interac-
tions. The lack of a significant Dd for Ha or Hb contraindicates the
influence of alternative binding conformations, although multiple
conformations have been previously observed in 2 and 3 by rotation
about the ethynyl linkers.16a,17,22 The stronger urea hydrogen bond to
ClÀ is formed with the more distant proton from the core, Hh, which
is apparent in the large shift (Dd 3.8 ppm) as compared to the
interior urea Hg. Similar shifts are observed upon titration with BrÀ
and IÀ (Fig. S4 and S7, ESI†).
Pyridine host 2, with only four hydrogen bond donors, has the
lowest Ka for the tested anions. As previously reported, protonation
of this class of receptor activates anion binding, increasing the Ka
Scheme 1 Synthesis of receptor 5. Proton assignments determined via 1H–13
HSQC and 1H–1H ROSY NMR spectroscopy.
C
Evidence of hydrogen bonding was also observed in the
X-ray crystal structure of 5ÁClÀ, which is shown in Fig. 3.23 The
chloride resides within a binding pocket created by the aryl
proton and the urea arms with a TBA+ cation in close proximity.
The central phenylacetylene carbons (C1–C9, C27–C29) form a
plane (Æ0.033 Å), which the chloride sits slightly above
(0.257(4) Å). The urea arms are twisted with one slightly above
the plane and the other slightly below the plane. The C(Hc)Á Á ÁCl
distance is 3.579(3) Å and the C(Hc)Á Á ÁCl angle is 1691. The
N(H)Á Á ÁCl distances vary greatly with the shortest distance at
3.212(3) Å and the longest distance measuring 3.732(3) Å. The
N(H)Á Á ÁCl angles vary from 1461 to 1701. The C(Hc)Á Á ÁCl total
distance is less than the sum of the van der Waals radii for the
component elements and is shorter than previously reported
examples of arene C(H)Á Á ÁCl contacts in anion hosts (3.538–
3.793 Å).14 The large angle and short distance fall well within
Fig. 2 1H NMR titration of 5 with TBA+ClÀ at 298 K; [5] = 0.69 mM in water
saturated CDCl3. Peak assignments refer to Scheme 1.
c
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selectivity or electronic properties of the host. Related computational
modeling has shown that substitution with electron withdrawing
groups can increase the hydrogen bond energy of benzene closer to
that of pyrrole.9 Further experiments with the phenyl core may help to
elucidate the mechanism of fluorescence in this class of sensor,
especially the influence of the pyridine ring in the parent receptor.
Work is underway to explore substituted phenyl cores with the goal of
achieving Kas on the same order or greater than found for 3.
This work was supported by NIH grant R01-GM087398; see
the ESI† for complete acknowledgments.
Notes and references
Fig. 3 X-ray crystal structure of 5ÁClÀ shown as ORTEP representation. Hydrogen
bond interactions are shown as dashed lines. Non-coordinating hydrogens, TBA+
counter cation and solvent have been omitted for clarity. Ellipsoids drawn at 50%
probability level.
1 J. L. Sessler, P. A. Gale and W.-S. Cho, Anion Receptor Chemistry,
Royal Society of Chemistry, Cambridge, 2006.
2 P. D. Beer and P. A. Gale, Angew. Chem., Int. Ed., 2001, 40, 486–516.
3 (a) F. G. Bordwell, Acc. Chem. Res., 1988, 21, 456–463; (b) There appears
to be discrepancy for the pKa of benzene in water, with values of 37 and
43 appearing most commonly. We chose to use the value reported in:
E. V. Anslyn and D. A. Dougherty, Modern Physical Organic Chemistry,
University Science Books, Sausalito, CA, 2006, p. 280.
4 G. R. Desiraju and T. Steiner, The Weak Hydrogen Bond: in Structural
Chemistry and Biology, Oxford University Press, Oxford, New York, 1999.
5 H.-J. Schneider, Angew. Chem., Int. Ed., 2009, 48, 3924–3977.
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2012, 10, 6951–6959.
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8 (a) H. Maeda, Y. Haketa and T. Nakanishi, J. Am. Chem. Soc., 2007, 129,
13661–13674; (b) B. Dong, T. Sakurai, Y. Honsho, S. Seki and H. Maeda,
J. Am. Chem. Soc., 2013, 135, 1284–1287; (c) Y. Terashima, M. Takayama,
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previously defined criteria for an aryl hydrogen bond (y > 1401,
d o 3.86 Å)4,24 and add credence for the importance of this C–H
hydrogen bond in anion binding.
The urea hydrogen bond distances provide further evidence for
the binding conformation observed in solid-state studies to exist in
solution. The urea hydrogen bonds are divided into two asymmetric
groups, where N2/N4 are on average 0.41 Å closer to Cl than N1/N3
(Hh and Hg, respectively). The average distance for N(Hg)ÁÁÁCl is
3.637 Å and the average distance for N(Hh)ÁÁÁCl is 3.213 Å. A longer
N(Hg)ÁÁÁCl distance would account for the smaller downfield shift
observed by 1H NMR spectroscopy. The solution and solid state
experiments provide a relative rank of the hydrogen bond lengths to
ClÀ, and perhaps strengths as follows: N(Hh) > C(Hc) > N(Hg).
UV-Vis and fluorescence spectroscopy experiments were per-
formed to evaluate the sensing ability of compound 5 (see Fig. S11
and S15 in the ESI†). The color change of 5was modest but allowed for
the determination of binding constants. ClÀ titrations of 5 have an
isosbestic point at 312 nm indicating a clean transition from free host
and guest to the final host:guest complex, which lends credence to the
1 : 1 host : guest model used for Ka determination. Crystallographic
evidence points to a higher order complex (1 : 2 or 2 : 1 host : guest)
being unlikely and these larger complexes would require an inter-
mediate complex, which is not evident in solution. Receptors 2 and 3
were previously shown to be good fluorescent sensors,16 and the
conjugated core of 5 should also lend itself to this application.
Excitation at 320 nm produced a fluorescence emission at 381 nm
with a Stoke’s shift of 5000 cmÀ1. Addition of one equivalent TBACl
12 Y. Hua, R. O. Ramabhadran, J. A. Karty, K. Raghavachari and
A. H. Flood, Chem. Commun., 2011, 47, 5979–5981.
13 V. S. Bryantsev and B. P. Hay, Org. Lett., 2005, 7, 5031–5034.
14 (a) H. Juwarker, J. M. Lenhardt, D. M. Pham and S. L. Craig, Angew.
Chem., Int. Ed., 2008, 47, 3740–3743; (b) C.-H. Lee, H.-K. Na,
D.-W. Yoon, D.-H. Won, W.-S. Cho, V. M. Lynch, S. V. Shevchuk
and J. L. Sessler, J. Am. Chem. Soc., 2003, 125, 7301–7306;
(c) F. Szemes, D. Hesek, Z. Chen, S. W. Dent, M. G. B. Drew,
A. J. Goulden, A. R. Graydon, A. Grieve, R. J. Mortimer, T. Wear,
J. S. Weightman and P. D. Beer, Inorg. Chem., 1996, 35, 5868–5879.
15 (a) C. N. Carroll, J. J. Naleway, M. M. Haley and D. W. Johnson,
Chem. Soc. Rev., 2010, 39, 3875–3888; (b) O. B. Berryman,
C. A. Johnson II, L. N. Zakharov, M. M. Haley and D. W. Johnson,
Angew. Chem., Int. Ed., 2008, 47, 117–120.
16 (a) J. M. Engle, C. N. Carroll, D. W. Johnson and M. M. Haley, Chem.
Sci., 2012, 3, 1105–1110; (b) C. N. Carroll, B. A. Coombs,
S. P. McClintock, C. A. Johnson, O. B. Berryman, D. W. Johnson
and M. M. Haley, Chem. Commun., 2011, 47, 5539–5541.
17 C. N. Carroll, O. B. Berryman, C. A. Johnson, L. N. Zakharov,
M. M. Haley and D. W. Johnson, Chem. Commun., 2009, 2520–2522.
caused a marked decrease in the fluorescence. The turn-off fluores- 18 (a) J. M. Heemstra and J. S. Moore, Org. Lett., 2004, 6, 659–662; (b) It
should be noted that this value is determined in CH3CN; in water
the bis(ethynyl)pyridiniums should still be more acidic than pyr-
cent response for chloride is the same as previously observed with
receptor 3. The fluorescence response of this class of sensors can be
idinium and thus have pKas o 5.
¨
¨
controlled by substitution at the para position of the phenylureas. In 19 I. Kaljurand, A. Ku¨tt, L. Soovali, T. Rodima, V. Maemets, I. Leito and
I. A. Koppel, J. Org. Chem., 2005, 70, 1019–1028.
the pyridine sensors 2 and 3, an electron donating group (OMe)
20 P. Thordarson, Chem. Soc. Rev., 2011, 40, 1305–1323.
21 D.-W. Yoon, D. E. Gross, V. M. Lynch, J. L. Sessler, B. P. Hay and
produced an ‘‘on–off’’ response; however, electron withdrawing
groups (NO2) led to an ‘‘off–on’’ response.16
C.-H. Lee, Angew. Chem., Int. Ed., 2008, 47, 5038–5042.
22 J. M. Engle, P. S. Lakshminarayanan, C. N. Carroll, L. N. Zakharov,
M. M. Haley and D. W. Johnson, Cryst. Growth Des., 2011, 11, 5144–5152.
23 Crystallographic data for 5 can be found in the ESI† and as CCDC
929532.
24 (a) R. Taylor and O. Kennard, J. Am. Chem. Soc., 1982, 104,
5063–5070; (b) B. P. Hay and V. S. Bryantsev, Chem. Commun.,
2008, 2417–2428; (c) P. A. Wood, F. H. Allen and E. Pidcock,
CrystEngComm, 2009, 11, 1563–1571.
In summary, replacement of a pyridyl unit with a phenyl moiety in
the bis(anilinoethynyl)arene class of anion receptors has provided a
new avenue of inquiry into aryl C–H hydrogen bonding. The impor-
tance of the phenyl hydrogen bond donor has been demonstrated
with solution and solid-state evidence for a strong C–H to ClÀ contact.
In addition, the structural modification has not negatively affected the
c
7242 Chem. Commun., 2013, 49, 7240--7242
This journal is The Royal Society of Chemistry 2013