A water soluble, anion-binding zwitterionic capsule based on electrostatic interactions between self-complementary hemispheres

Article abstract of DOI:10.1039/b926149d

A water soluble anion receptor is reported that binds bromide in aqueous solution via CH...Br^- interactions in a dimeric capsule.

Full text of DOI:10.1039/b926149d

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A water soluble, anion-binding zwitterionic capsule based on electrostatic
interactions between self-complementary hemispheresw
Ammie L. Cresswell, Marc-Oliver M. Piepenbrock and Jonathan W. Steed*
Received (in Cambridge, UK) 11th December 2009, Accepted 12th February 2010
First published as an Advance Article on the web 25th February 2010
DOI: 10.1039/b926149d
A water soluble anion receptor is reported that binds bromide in
aqueous solution via CHꢀ ꢀ ꢀBrꢁ interactions in a dimeric capsule.
In the design of receptors for anionic guests1–4 there is a
tension between the selection of a cationic receptor or a
neutral one. Cationic receptors exhibit strong ion-pairing
interactions to anions, but target anion binding is in competition
with the receptor’s charge-balancing anion(s).5 Conversely,
neutral anion receptors must also accommodate a cationic
counterion and may exhibit intrinsically weaker binding.6
Competitive solvation effects are potentially highly significant
Scheme 1 Zwitterionic receptors 1 and 2.
in both cases depending on the medium. One interesting, but
rarely deployed, compromise is the use of zwitterionic receptors.
There have been a few effective examples of zwitterionic
receptors based on macrobicyclic cage receptors reported by
Schmidtchen’s group.7–9 These results demonstrate that in
general the anionic and cationic ends of the receptor must be
well separated by a rigid linker to avoid self-inhibition by the
host and consequently zwitterionic receptors are rare. We now
report a simple tripodal zwitterion that forms a robust anion-
Fig. 1 X-Ray molecular structure of 2ꢀ9H2O (ellipsoids 50%).
binding capsule even in the absence of significant hydrogen
bonding interactions. In contrast, a non-self-complementary
The structure confirms the zwitterionic nature of the molecule.
The carboxylate groups adopt an ‘out’ conformation
maximising the distance between them and presumably
contributing to the water solubility of the molecule. The
included water molecules form an infinite hydrogen bonded
layer that links the carboxylate functionalities together.
A notable feature is the bridging of two carboxylate groups
on adjacent molecules by two water molecules to give an
R44(12) motif,17 within a much more extensive network.
control compound exhibits very little anion affinity.
Zwitterions 1 and 2 (Scheme 1) are readily prepared by
reaction of either ethyl isonicotinate or ethyl nicotinate with
1,3,5-tribromomethyl-2,4,6-triethylbenzene10 followed by
hydrolysis with sodium hydroxide in water to give the
carboxylate of the corresponding ethyl ester derivatives.11
Compound 2 has the meta substitution pattern that has proved
highly successful in anion binding aminopyridinium
derivatives12–16 and the anion binding properties of this host
in water were assessed by 1H NMR spectroscopic titration.
However, the highly competitive nature of the aqueous
medium resulted in no chemical shift changes on titration
with a range of both common and unusual anion salts, namely
NaCl, NaI, MgATP, C6H3(COONa)3 and K3[Al(oxalate)3]ꢀH2O.
Similarly negative results were obtained in methanol and
hence, in addition to the nature of the solvent, the proximity
of the anionic carboxylates to the intended binding cavity and
the lack of hydrogen bond donor functionality also mitigate
against effective anion binding behaviour. Compound 2 was
characterised by X-ray crystallography (Fig. 1)z as a nonahydrate.
In the presence of excess HPF6 it proved possible to isolate a
monoprotonated form of 2, which precipitated upon acidification
of an aqueous solution of the receptor. The X-ray structure of
2ꢀHPF6ꢀ2H2O is shown in Fig. 2 and despite being isolated in
ꢁ
the presence of excess acid contains only a single PF6 anion.
The compound exists as an infinite 1D ribbon via CO2ꢁꢀꢀꢀHO2C
hydrogen bonds with the X-ray data suggesting that the acidic
Department of Chemistry, Durham University, South Road, Durham,
UK DH1 3LE. E-mail: jon.steed@durham.ac.uk;
Fax: +44 (0)191 384 4737; Tel: +44 (0)191 334 2085
w Electronic supplementary information (ESI) available: NMR
spectroscopic titration and synthetic experimental details. CCDC
758080, 758081 and 758114. For ESI and crystallographic data in
CIF or other electronic format see DOI: 10.1039/b926149d
Fig. 2 X-Ray crystal structure of 2ꢀHPF6ꢀ2H2O (ellipsoids 50%).
Chem. Commun., 2010, 46, 2787–2789 | 2787
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proton is shared almost equally between the two carboxylate
groups in a fashion characteristic of a strong hydrogen
bond.18–21 The Oꢀ ꢀ ꢀO distance in this interaction is also very
short at just 2.452(2) A, comparable to the Oꢀ ꢀ ꢀO separations
found in oxonium ion species, for example.22,23 The
carboxylate functionalities again adopt an ‘out’ conformatioꢁn
and are not directed towards the tripodal cavity. The PF6
anion is situated in between a pair of pyridinium groups
engaging in anion–p interactions24–26 and does not take part
in hydrogen bonding to the carboxylic acid group, nor to the
pyridiniumꢁCH groups.12
such that each carboxylate functionality is sandwiched in
between two pyridinium groups of the opposite zwitterion.
The entire assembly exhibits crystallographic threefold
symmetry in space group R3 with one third of the capsule
unique. A Na+ cation and solvent water are disordered on the
outside of the capsule. The bromide anion is held entirely by
CHꢀ ꢀ ꢀBrꢁ hydrogen bonding interactions to the pyridinium
CH group in a fashion that we have shown previously is an
effective anion binding mode.12
A loosely related, neutral tripodal receptor has been shown
to form a dimeric capsule containing two Fꢁ ions and six
water molecules recently, but this system is based on strong
hydrogen bonding interactions.27 While there have been a few
reports of electrostatically self-assembled capsules that exist in
solution, they remain extremely rare.28–32 The advantage,
however, is that electrostatics offer the possibility of self-
assembly in highly competitive media such as water, whereas
hydrogen bonding interactions are generally overwhelmed by
solvation.
The stability and existence of the anionic capsule [(1)2Br]ꢁ
in solution were probed by negative ion ESI mass
spectrometry which showed a peak at m/z 1213 corresponding
to the anion [(1)2Br]ꢁ with a calculated isotopic distribution
consistent with the proposed formulation. The capsule proved
to be sufficiently soluble in D2O to obtain an 1H NMR
spectrum which showed sharp resonances consistent with a
single, threefold symmetric species. Attempts were made to
remove the NaBr by treating the capsule with AgPF6 in water.
Following removal of the precipitated AgBr the 1H NMR
spectrum was re-recorded and showed a small but significant
change in the chemical shift of the host resonances, particularly
those assigned to the CH protons ortho to the pyridinium
groups. However, it proved impossible to prepare a sample
that was completely free of bromide and hence quantitative
NMR measurements were not attempted.
The PF6 complex 2ꢀHPF6ꢀ2H2O is insoluble in water but
its anion affinity was assessed in DMSO-d6 solution. Under
+
these conditions the receptor does bind halides (NBu4 salts)
with modest affinity. Chemical shift changes of ca. 0.8 ppm
were observed in the case of chloride and binding constants for
Clꢁ and Brꢁ are log K11 = 2.17(2) and 1.98(2), respectively.
In contrast to 2 which is readily isolated as a free zwitterion,
difficult to protonate and exhibits very little anion affinity, the
para isomer 1 proved to be extremely difficult to obtain in a
guest-free form. The hydrolysis of the bromide salt of the
precursor ester by NaOH results in the formation of NaBr as a
byproduct, and it proved extremely difficult to obtain 1 free of
NaBr despite repeated recrystallisation from water. The
reason for this behaviour is immediately apparent in the
X-ray crystal structure of the product (Fig. 3) which reveals
a remarkable 2
: 1 host :
Brꢁ self-assembled capsular
structure of formula Na[(1)2Br]ꢀ13H2O in which a bromide
ion is completely enclosed by two zwitterions of 1 with the
carboxylate groups of each zwitterion mutually interdigitated
In conclusion we have prepared a water soluble zwitterionic
receptor (1) that exhibits strong affinity for bromide anion due
to its unique ability to form a capsular complex. The
non-capsule-forming analogue (2) does not bind anions in
water or other polar solvents. Both the electrostatically driven
self-assembly mode and the use of ‘soft’ CHꢀ ꢀ ꢀanion inter-
actions to give effective binding in water are surprising features
of the system and suggest a new strategy towards anion
templated capsules in highly competitive media.
We thank EPSRC for support of this work.
Notes and references
z Crystal data for 2ꢀ9H2O: C33H51N3O15, M = 729.77, 0.30 ꢃ 0.25 ꢃ
ꢀ
0.15 mm, triclinic, space group P1 (No. 2), a = 10.5704(15),
b = 17.283(2), c = 19.733(3) A, a = 82.800(3)1, b = 89.161(3)1,
=
g = 80.989(3)1, V = 3532.4(9) A3, Z = 4, Dc = 1.372 g cmꢁ3, F000
1560, MoKa radiation, l = 0.71073 A, T = 120(2) K, 2ymax = 46.71,
31 569 reflections collected, 10 199 unique (Rint = 0.0398). Final
GooF = 1.019, R1 = 0.0616, wR2 = 0.1500, R indices based on
7995 reflections with I > 2s(I) (refinement on F2), 947 parameters,
0 restraints. Lp and absorption corrections applied, m = 0.108 mmꢁ1
.
Crystal data for 2ꢀHPF6ꢀ2H2O: C33H38F6N3O8P,
M = 749.63,
ꢀ
colourless block, 0.40 ꢃ 0.20 ꢃ 0.08 mm, triclinic, space group P1
(No. 2), a = 11.9455(4), b = 12.1050(5), c = 12.7773(5) A, a =
77.5830(10)1, b = 67.744(2)1, g = 88.694(2)1, V = 1666.44(11) A3,
Z = 2, Dc = 1.494 g cmꢁ3, F000 = 780, MoKa radiation, l = 0.71073 A,
T = 120(2) K, 2ymax = 55.01, 21 557 reflections collected, 7660 unique
Fig. 3 Two views of the [(1)2Br]ꢁ anionic capsule in the X-ray
structure of Na[(1)2Br]ꢀ13H2O. Bromide anion shown in space filling
representation.
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(Rint = 0.0358). Final GooF = 1.049, R1 = 0.0497, wR2 = 0.1289,
R indices based on 5886 reflections with I > 2s(I) (refinement on F2),
480 parameters, 6 restraints. Lp and absorption corrections applied,
m = 0.173 mmꢁ1. Crystal data for Na[(1)2Br]ꢀ13H2O: C66H92BrN6NaO25,
M = 1472.36, colourless cube, 0.13 ꢃ 0.12 ꢃ 0.12 mm, trigonal,
space group R3 (No. 146), a = b = 17.636(3), c = 20.817(4) A,
V = 5607.2(16) A3, Z = 3, Dc = 1.308 g cmꢁ3, F000 = 2328, SMART
6000, MoKa radiation, l = 0.71073 A, T = 120(2) K, 2ymax = 55.01,
18976 reflections collected, 5532 unique (Rint = 0.0484). Final GooF =
1.004, R1 = 0.0506, wR2 = 0.1246, R indices based on 4283 reflections
with I > 2s(I) (refinement on F2), 343 parameters, 91 restraints.
Lp and absorption corrections applied, m = 0.635 mmꢁ1. Absolute
structure parameter = 0.517(16); racemic twin.
14 V. Amendola, M. Boiocchi, L. Fabbrizzi and A. Palchetti,
Chem.–Eur. J., 2005, 11, 5648–5660.
15 M. H. Filby, S. J. Dickson, N. Zaccheroni, L. Prodi, S. Bonacchi,
M. Montalti, C. Chiorboli, M. J. Paterson, T. D. Humphries and
J. W. Steed, J. Am. Chem. Soc., 2008, 130, 4105–4113.
16 Y. Bai, B.-G. Zhang, C. Y. Duan, D.-B. Dang and Q.-J. Meng,
New J. Chem., 2006, 30, 266–271.
17 J. Bernstein, R. E. Davis, L. Shimoni and N.-L. Chang,
Angew. Chem., Int. Ed. Engl., 1995, 34, 1555–1573.
18 G. A. Jeffrey, An Introduction to Hydrogen Bonding, OUP, Oxford,
1st edn, 1997.
19 C. C. Wilson, K. Shankland and N. Shankland, Z. Kristallogr.,
2001, 216, 303–306.
20 T. Steiner, C. C. Wilson and I. Majerz, Chem. Commun., 2000,
1231–1232.
21 T. Steiner, Angew. Chem., Int. Ed., 2002, 41, 48–76.
22 A. Bino and F. A. Cotton, J. Am. Chem. Soc., 1979, 101,
4150–4154.
23 M. Calleja, S. A. Mason, P. D. Prince, J. W. Steed and
C. Wilkinson, New J. Chem., 2001, 25, 1475–1478.
24 B. L. Schottel, H. T. Chifotides and K. R. Dunbar, Chem. Soc.
Rev., 2008, 37, 68–83.
25 T. J. Mooibroek, C. A. Black, P. Gamez and J. Reedijk,
Cryst. Growth Des., 2008, 8, 1082–1093.
26 B. P. Hay and V. S. Bryantsev, Chem. Commun., 2008, 2417–2428.
27 M. Arunachalam and P. Ghosh, Chem. Commun., 2009,
5389–5391.
28 R. Fiammengo, P. Timmerman, J. Huskens, K. Versluis, A. J. R.
Heck and D. N. Reinhoudt, Tetrahedron, 2002, 58, 757–764.
29 F. Corbellini, R. M. A. Knegtel, P. D. J. Grootenhuis, M.
Crego-Calama and D. N. Reinhoudt, Chem.–Eur. J., 2005, 11,
298–307.
30 F. Corbellini, F. W. B. van Leeuwen, H. Beijleveld, H. Kooijman,
A. L. Spek, W. Verboom, M. Crego-Calama and D. N. Reinhoudt,
New J. Chem., 2005, 29, 243–248.
31 G. V. Oshovsky, D. N. Reinhoudt and W. Verboom, Eur. J. Org.
Chem., 2006, 2810–2816.
1 C. Caltagirone and P. A. Gale, Chem. Soc. Rev., 2009, 38, 520–563.
2 J. L. Sessler, P. A. Gale and W.-S. Cho, Anion Receptor Chemistry,
Royal Society of Chemistry, Cambridge, 2006.
3 T. Gunnlaugsson, M. Glynn, G. M. Tocci, P. E. Kruger and
F. M. Pfeffer, Coord. Chem. Rev., 2006, 250, 3094–3117.
4 J. W. Steed, Chem. Soc. Rev., 2009, 38, 506–519.
5 M. M. G. Antonisse and D. N. Reinhoudt, Chem. Commun., 1998,
443–448.
6 J. W. Steed and J. L. Atwood, Supramolecular Chemistry,
Wiley-Blackwell, Chichester, 2nd edn, 2009.
7 K. Worm, F. P. Schmidtchen, A. Schier, A. Schafer and M. Hesse,
Angew. Chem., Int. Ed. Engl., 1994, 33, 327–329.
8 M. Berger and F. P. Schmidtchen, J. Am. Chem. Soc., 1999, 121,
9986–9993.
9 K. Worm and F. P. Schmidtchen, Angew. Chem., Int. Ed. Engl.,
1995, 34, 65–66.
10 K. J. Wallace, R. Hanes, E. Anslyn, J. Morey, K. V. Kilway and
J. Siegel, Synthesis, 2005, 2080–2083.
11 W. J. Belcher, M. Fabre, T. Farhan and J. W. Steed, Org. Biomol.
Chem., 2006, 4, 781–786.
12 K. J. Wallace, W. J. Belcher, D. R. Turner, K. F. Syed and
J. W. Steed, J. Am. Chem. Soc., 2003, 125, 9699–9715.
13 L. O. Abouderbala, W. J. Belcher, M. G. Boutelle, P. J. Cragg,
M. Fabre, J. Dhaliwal, J. W. Steed, D. R. Turner and
K. J. Wallace, Chem. Commun., 2002, 358–359.
32 J. Kim, D. Ryu, Y. Sei, K. Yamaguchi and K. H. Ahn, Chem.
Commun., 2006, 1136–1138.
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