Anion-controlled ion-pair recognition of paraquat by a bis(m-phenylene)-32- crown-10 derivative heteroditopic host

Article abstract of DOI:10.1021/jo802683d

It has been demonstrated that the complexation of the divalent salts of paraquat can be greatly improved (a K_a increase up to 219 times was observed) by the introduction of ion-pair recognition through use of urea moieties on the crown ether. This improvement is controlled by not only the solvent polarity but also the nature of the anion. Furthermore, it was found that the binding motif for paraquat guest incorporation into the heteroditopic host is anion-controlled in the solid state. The host-guest complex is a pseudorotaxane in the solid state when the two counterions of paraquat are trifluoroacetate anions while it is a taco complex when the two counterions are hexafluorophosphate or chloride anions.

Full text of DOI:10.1021/jo802683d

Anion-Controlled Ion-Pair Recognition of Paraquat by a
Bis(m-phenylene)-32-crown-10 Derivative Heteroditopic Host
Kelong Zhu, Shijun Li, Feng Wang, and Feihe Huang*
Department of Chemistry, Zhejiang UniVersity, Hangzhou 310027, People’s Republic of China
fhuang@zju.edu.cn
ReceiVed December 06, 2008
It has been demonstrated that the complexation of the divalent salts of paraquat can be greatly improved
(a Ka increase up to 219 times was observed) by the introduction of ion-pair recognition through use of
urea moieties on the crown ether. This improvement is controlled by not only the solvent polarity but
also the nature of the anion. Furthermore, it was found that the binding motif for paraquat guest
incorporation into the heteroditopic host is anion-controlled in the solid state. The host-guest complex
is a pseudorotaxane in the solid state when the two counterions of paraquat are trifluoroacetate anions
while it is a taco complex when the two counterions are hexafluorophosphate or chloride anions.
Introduction
of crystals.2d The control of how the guest is incorporated into
the host and the relative positional changes that take place within
the complexes is critical for the preparation of molecular
machines and storage materials.3,4
Ion-pair recognition has attracted much attention in recent
years for its great potential for biological, analytical, and
environmental applications.5 By the combination of anion and
cation receptors, the heteroditopic hosts used in ion-pair
recognition often exhibit cooperative and allosteric effects,
whereby the association of one ion alters the binding affinity
of the counterion through electrostatic and conformational
effects. Since Reetz et al. reported one of the first successful
Anions control many important biological processes in
nature.1 For example, anions control the information processing
in retina1a and arginine metabolism in chicken kidney and
liver.1b The cation (such as sodium and calcium cations)
conductance in human red blood cells is chloride anion-
controlled induced by oxidation.1g In artificial systems, people
have elegantly used anions to control the formation of
pseudorotaxanes,2a fabrication of supramolecular capsules,2b
operation of molecular machines,2c and morphological evolution
* Fax/phone: +86-571-8795-3189.
(1) (a) Robert, F. M.; Ramon, F. D. Science 1973, 181, 266–268. (b) Grazi,
E.; Magri, E.; Balboni, G. Eur. J. Biochem. 1975, 60, 431–436. (c) Christianson,
D. W.; Lipscomb, W. N. Acc. Chem. Res. 1989, 22, 62–69. (d) Glidewell, C.
Chem. Brit. 1990, 26, 137–140. (e) Moss, B. Chem. Ind. 1996, 407–411. (f) The
Supramolecular Chemistry of Anions; Bianchi, A., Bowman-James, K., Garcia-
Espana, E., Eds.; VCH: Weinheim, Germany, 1997. (g) Duranton, C.; Huber,
S. M.; Lang, F. J. Physiol. 2002, 539, 847–855.
(2) (a) Wisner, J. A.; Beer, P. D.; Berry, N. G.; Tomapatanaget, B Proc.
Natl. Acad. Sci. U.S.A. 2002, 99, 4983–4986. (b) Oshovsky, G. V.; Reinhoudt,
D. N.; Verboom, W. J. Am. Chem. Soc. 2006, 128, 5270–5278. (c) Lin, C.-F.;
Lai, C.-C.; Liu, Y.-H.; Peng, S.-M.; Chiu, S.-H. Chem.-Eur. J. 2007, 13, 4350–
4355. (d) Fang, H.; Li, L.; Yang, Y.; Yan, G.; Li, G. Chem. Commun. 2008, 9,
1118–1120.
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E. W. Angew. Chem., Int. Ed. 2000, 39, 1285–1288. (b) Mertz, E.; Zimmerman,
S. C. J. Am. Chem. Soc. 2003, 125, 3424–3425. (c) Hernandez, J. V.; Kay, E. R.;
Leigh, D. A. Science 2004, 306, 1532–1537. (d) Petitjean, A.; Khoury, R. G.;
Kyritsakas, N.; Lehn, J.-M. J. Am. Chem. Soc. 2004, 126, 6637–6647. (e) Zhang,
J.; Huang, F.; Li, N.; Wang, H.; Gibson, H. W.; Gantzel, P.; Rheingold, A. L.
J. Org. Chem. 2007, 72, 8935–8938. (f) Chang, T.; Pieterse, K.; Broeren,
M. A. C.; Kooijman, H.; Spek, A. L.; Hilbers, P. A. J.; Meijer, E. W. Chem.-
Eur. J. 2007, 13, 7883–7889.
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1322 J. Org. Chem. 2009, 74, 1322–1328
10.1021/jo802683d CCC: $40.75 2009 American Chemical Society
Published on Web 01/06/2009

Anion-Controlled Ion-Pair Recognition of Paraquat
FIGURE 1. Compounds used in this study.
examples of heteroditopic receptors for associated ion-pairs in
1991,5c much work has been done in this field.5 With the
assistance of the ion-pair recognition process, the binding affinity
of the host can be enhanced and even the binding selectivity of
the host can be reversed.5f,n The heteroditopic host can be
developed to act as an efficient extraction and carrier transport-
ing reagent for environmentally deleterious pollutants.5d,e The
ion-pair recognition can also play an important role in control-
ling the geometry of self-assembly. For instance, by the
complementary of nitrate, a discrete host-guest assembly can
be formed in a Ag+-ligand system.5l Also the assembly of a
22-component complex can be mediated by the cooperation of
ligands, cations, and anions.5g By the introduction of ion-pair
recognition, it has been demonstrated that the strong binding
of biologically important reagents can be achieved even in
water.5h-k Though the application of ion-pair recognition to
improve the complexation of monovalent organic or inorganic
salts has been widely studied up to now, to the best of our
knowledge, much less has been explored on the ion-pair
recognition of divalent organic salts.
ture.6 It and its derivatives have been widely used in the
fabrication of numerous supramolecular systems with crown
ethers including bis(m-phenylene)-32-crown-10 (BMP32C10,
1) due to their easy availability and interesting physicochemical
properties.3e,4,7 The improvement of the binding of paraquat and
its derivatives is not only important for environmental monitor-
ing and human health,3e,6 but it is also critical for the fabrication
of large supramolecular systems.8 Herein, we report the synthesis
of a heteroditopic BMP32C10 derivative receptor 2 (Figure 1),
which was designed to have a BMP32C10 moiety for binding
the dicationic bipyridinium part of paraquat 3 and two urea
groups for binding the two anions of paraquat 3,1f,7,9 and its
complexation with paraquat 3 with different anions with the
objective of improving the binding of paraquat.
Results and Discussion
A. Synthesis of Heteroditopic Bis(m-phenylene)-32-crown-
10 Derivative Host 2. The key starting material 410 and bis(m-
(6) (a) Russell, R. K. J. Agric. Food Chem. 1978, 26, 1460–1463. (b)
Mastichiadis, C.; Kakabakos, S. E.; Christofidis, I.; Koupparis, M. A.; Willetts,
C.; Misiakos, K. Anal. Chem. 2002, 74, 6064–6072. (c) Merino, F.; Rubio, S.;
Perez-Bendito, D. Anal. Chem. 2004, 76, 3878–3886. (d) Bacigalupo, M. A.;
Meroni, G.; Mirasoli, M.; Parisi, D.; Longhi, R. J. Agric. Food Chem. 2005, 53,
216–219. (e) Bacigalupo, M. A.; Meroni, G. J. Agric. Food Chem. 2007, 55,
3823–3828. (f) Zhang, J.; Zhai, C.; Wang, F.; Zhang, C.; Li, S.; Zhang, M.; Li,
N.; Huang, F. Tetrahedron Lett. 2008, 49, 5009–5012.
(7) Selected publications on the bis(m-phenylene)-32-crown-10/paraquat
recognition motif:(a) Allwood, B. L.; Shahriari-Zavareh, H.; Stoddart, J. F.;
Williams, D. J. J. Chem. Soc., Chem. Commun. 1987, 1058–1061. (b) Jones,
J. W.; Zakharov, L. N.; Rheingold, A. L.; Gibson, H. W. J. Am. Chem. Soc.
2002, 124, 13378–13379. (c) Huang, F.; Gibson, H. W J. Am. Chem. Soc. 2004,
126, 14738–14739. (d) Huang, F.; Guzei, I. A.; Jones, J. W.; Gibson, H. W.
Chem. Commun. 2005, 1693–1695. (e) Huang, F.; Nagvekar, D. S.; Slebodnick,
C.; Gibson, H. W. J. Am. Chem. Soc. 2005, 127, 484–485. (f) Huang, F.; Lam,
M.; Mahan, E. J.; Rheingold, A. L.; Gibson, H. W. Chem. Commun. 2005, 3268–
3270. (g) Huang, F.; Gantzel, P.; Nagvekar, D. S.; Rheingold, A. L.; Gibson,
H. W. Tetrahedron Lett. 2006, 47, 7841–7844. (h) Yang, Y.; Hu, H.-Y.; Chen,
C.-F. Tetrahedron Lett. 2007, 48, 3505–3509.
(8) Huang, F.; Fronczek, F. R.; Gibson, H. W J. Am. Chem. Soc. 2003, 125,
9272–9273. Huang, F.; Gibson, H. W.; Bryant, W. S.; Nagvekar, D. S.; Fronczek,
F. R. J. Am. Chem. Soc. 2003, 125, 9367–9371. Huang, F.; Switek, K. A.;
Zakharov, L. N.; Fronczek, F. R.; Slebodnick, C.; Lam, M.; Golen, J. A.; Bryant,
W. S.; Mason, P. E.; Rheingold, A. L.; Ashraf-Khorassani, M.; Gibson, H. W.
J. Org. Chem. 2005, 70, 3231–3241.
(9) Amendola, V.; Bonizzoni, M.; Esteban-Go´mez, D.; Fabbrizzi, L.;
Licchelli, M.; Sanceno´n, F.; Taglietti, A. Coord. Chem. ReV. 2006, 250, 1451–
1470.
Paraquat (N,N′-dimethyl-4,4′-bipyridinium) is an effective but
highly toxic herbicide widely used in agriculture and horticul-
(5) Reviews on ion-pair recognition:(a) Beer, P. D.; Gale, P. A. Angew.
Chem., Int. Ed. 2001, 40, 486–516. (b) Gale, P. A Coord. Chem. ReV. 2003,
240, 191–221. Selected publications on ion-pair recognition: (c) Reetz, M. T.;
Niemeyer, C. M.; Harms, K. Angew. Chem., Int. Ed. Engl. 1991, 30, 1474–
1476. (d) Beer, P. D.; Hopkins, P. K.; McKinney, J. D. Chem. Commun. 1999,
1253–1254. (e) White, D. J.; Laing, N.; Miller, H.; Parsons, S.; Coles, S.; Tasker,
P. A. Chem. Commun. 1999, 2077–2078. (f) Shukla, R.; Kida, T.; Smith, B. D.
Org. Lett. 2000, 2, 3099–3102. (g) Shi, X.; Fettinger, J. C.; Davis, J. T. Angew.
Chem., Int. Ed. 2001, 40, 2827–2831. (h) Niikura, K.; Anslyn, E. V. J. Org.
Chem. 2003, 68, 10156–10157. (i) Tobey, S. L.; Anslyn, E. V. J. Am. Chem.
Soc. 2003, 125, 10963–10970. (j) Tobey, S. L.; Anslyn, E. V. J. Am. Chem.
Soc. 2003, 125, 14807–14815. (k) Wright, A. T.; Anslyn, E. V. Org. Lett. 2004,
6, 1341–1344. (l) Turner, D. R.; Spencer, E. C.; Howard, J. A. K.; Tocherb,
D. A.; Steed, J. W. Chem. Commun. 2004, 1352–1353. (m) Domenico, G.;
Giuseppe, G.; Anna, N.; Andrea, P.; Sebastiano, P.; Melchiorre, F. P.; Marta,
P.; Ilenia, P. Angew. Chem., Int. Ed. 2005, 44, 4892–4896. (n) Lankshear, M. D.;
Dudley, I. M.; Chan, K-M.; Beer, P. D. New J. Chem. 2007, 31, 684–690. (o)
Lankshear, M. D.; Dudley, I. M.; Chan, K.-M.; Cowley, A. R.; Santos, S. M.;
Felix, V.; Beer, P. D. Chem.-Eur. J. 2008, 14, 2248–2263. (p) Cametti, M.;
Nissinen, M.; Dalla Cort, A.; Mandolini, L.; Rissanen, K. J. Am. Chem. Soc.
2007, 129, 3641–3648. (q) Wintergerst, M. P.; Levitskaia, T. G.; Moyer, B. A.;
Sessler, J. L.; Delmau, L. H. J. Am. Chem. Soc. 2008, 130, 4129–4139. (r) Sessler,
J. L.; Kim, S. K.; Gross, D. E.; Lee, C.-H.; Kim, J. S.; Lynch, V. M. J. Am.
Chem. Soc. 2008, 130, 13162–13166. (s) Zhu, K.; Zhang, M.; Wang, F.; Li, N.;
Li, S.; Huang, F. New J. Chem. 2008, 32, 1827–1830.
(10) Gibson, H. W.; Nagvekar, D. S. Can. J. Chem. 1997, 75, 1375–1384.
J. Org. Chem. Vol. 74, No. 3, 2009 1323

Zhu et al.
a
SCHEME 1. Synthesis of Heteroditopic Bis(m-phenylene)-32-crown-10 Derivative Host 2
a Reagents and conditions: (a) potassium phthalimide, DMF, 90 °C, 91%; (b) (i) hydrazine monohydrate, CH3OH, reflux, (ii) NaOH, H2O, 89% (two
steps); (c) phenylisocyanate, CHCl3, N2, 95%.
solution (see the Supporting Information), the same as those of
1 with 3.7 Positive electrospray ionization mass spectra in
CH3CN (see the Supporting Information) of equimolar mixtures
of 2 and 3a, 2 and 3b, and 2 and 3c gave strong mass fragments
of [2·3-2X]2+: m/z 509.3 (100%) for [2·3a-2PF6]2+, 509.3
(100%) for [2 · 3b-2Cl]2+
,
and 509.2 (100%) for
[2·3c-2CF3COO]2+, respectively. Also a common mass frag-
ment corresponding to [2·3-X]+ was found: m/z 1163.4 (35%)
for [2·3a-PF6]+, 1053.5 (25%) for [2·3b-Cl]+, and 1131.5
(27%) for [2·3c-CF3COO]+. These results confirmed the 1:1
complexation stoichiometry between 2 and 3.
The proton NMR spectra of equimolar (2.00 mM) acetonitrile
solutions of 2 and 3 (Figures 3-5) showed the complexation is
a fast exchange system as the reported complexation between
1 and 3.7 The complexation was stronger than that of 1 with 3
on the basis of the significant upfield shifts of the bipyridinium
protons (H1 and H2) and methyl protons (H3) of 3 and the
aromatic protons (H2a and H2b) and R-ethyleneoxy protons (H2R)
of 2. The phenyl protons (H2f, H2g, and H2h) and the urea protons
(H2d and H2e) of 2 moved downfield after complexation. The
changes of the chemical shifts of H2d and H2e after the
complexation between 2 and 3a (0.01 and 0.02 ppm) are
significantly smaller than those after the complexation between
2 and 3b (1.29 and 1.64 ppm) and those after the complexation
between 2 and 3c (1.57 and 1.63 ppm), which is attributed to
the very weak binding affinity of the urea portion to the large,
diffusely charged hexafluorophosphate anion compared with the
case of the chloride or trifluoroacetate anion.9 More interestingly,
the three peaks corresponding to ethyleneoxy protons (H2R, H2ꢀ,
H2γ, and H2δ) of 2 merged together to become one broad peak
upon complexation of 2 with 3a or 3b (spectra a and b in Figure
3 and spectra a and b in Figure 4), while clearly three separate
peaks were observed for these ethyleneoxy protons after the
complexation of 2 with 3c (spectra a and b in Figure 5). These
differences indicated that the complexation of 2 with 3c in
solution might have a different host-guest complexation
geometry from the complexation of 2 with 3a or 3b, resulting
from the differences in the counteranions of the paraquat salt
guests 3.
FIGURE 2. Job plot showing the 1:1 stoichiometry of the complex
between 2 and 3c in CH3CN:CH3OH (9:1, v:v) by plotting the
absorbance intensity at λ ) 376 nm (the host-guest charge transfer
band) against the mole fraction of the host. [2]0 and [3c]0 are initial
concentrations of 2 and 3c. [2]0 + [3c]0 ) 1.00 mM.
phenylene)-32-crown-10 (BMP32C10, 1)11 were synthesized
according to literature procedures. The diamino intermediate 6
was synthesized according to a similar method for monofunc-
tionalization of a phenyl crown ether reported by Gibson et al.12
As illustrated in Scheme 1, the reaction of 4 with excess
potassium phthalimide afforded 5. The diamino intermediate 6
was obtained from the hydrazinolysis of 5 in methanol in good
yield. The bis(m-phenylene)-32-crown-10 derivative heterodi-
topic host 2 was obtained in 95% yield by the reaction of 6
with phenylisocyanate in CHCl3.
B. Complexation of Heteroditopic Bis(m-phenylene)-32-
crown-10 Derivative Host 2 with Paraquat 3. A Job plot13
(Figure 2) based on UV-vis spectroscopy absorbance data in
CH3CN:CH3OH (9:1, v:v) demonstrated that the complex of 2
with 3c was of 1:1 stoichiometry in solution. The complexes
of 2 with 3a and 2 with 3b also have a 1:1 stoichiometry in
(11) Bryant, W. S.; Jones, J. W.; Mason, P. E.; Guzei, I. A.; Rheingold,
A. L.; Nagvekar, D. S.; Gibson, H. W. Org. Lett. 1999, 1, 1001–1004.
(12) Gibson, H. W.; Nagvekar, D. S.; Yamaguchi, N.; Wang, F.; Bryant,
W. S. J. Org. Chem. 1997, 62, 4798–4803.
C. Association Constant Comparison between the
Complexation of 2 with 3 and That of 1 with 3. The yellow
color, which resulted from charge transfer between electron-
(13) Job, P. Ann. Chim. 1928, 9, 113–203.
1324 J. Org. Chem. Vol. 74, No. 3, 2009

Anion-Controlled Ion-Pair Recognition of Paraquat
1
FIGURE 3. Partial H NMR spectra (400 MHz, CD3CN, 22 °C) of 2.00 mM 2 (a), 2.00 mM 2 and 3a (b), 2.00 mM 3a (c), 2.00 mM 1 and 3a
(d), and 2.00 mM 1 (e).
1
FIGURE 4. Partial H NMR spectra (400 MHz, CD3CN, 22 °C) of 2.00 mM 2 (a), 2.00 mM 2 and 3b (b), 2.00 mM 3b (c), 2.00 mM 1 and 3b
(d), and 2.00 mM 1 (e).
FIGURE 5. Partial 1H NMR spectra (400 MHz, CD3CN, 22 °C) of 2.00 mM 2 (a), 2.00 mM 2 and 3c (b), 2.00 mM 3c (c), 2.00 mM 1 and 3c (d),
and 2.00 mM 1 (e).
rich aromatic rings of the host and electron-poor pyridinium
rings of the guest, of equimolar (2.00 mM) CH3CN:CH3OH (9:
1, v:v) solutions of 2 and 3 was deeper than that of the
corresponding solutions of 1 and 3. This gave direct evidence
that the binding of the anions with the urea groups can enhance
the binding of the crown ether cavity to the dicationic bipyri-
dinium part through ion-pair recognition. The association
constant (Ka) values of complexes 1·3 and 2·3, as shown in
Table 1, were determined by probing the charge-transfer band
of the complexes by UV-vis spectroscopy and employing a
titration method (Figure 6 as well as Figures S15-S36 in the
Supporting Information). All complexes 2·3 exhibited Ka
increases compared with the corresponding complexes 1·3
induced by the ion-pair recognition. However, there are two
things worth noting. First, when the solvent polarity was
reduced, the Ka increase rose. For example, the Ka increase from
J. Org. Chem. Vol. 74, No. 3, 2009 1325

Zhu et al.
TABLE 1. Association Constants (Ka/M-1) for the 1:1 Complexes between Hosts 1 and 2 and Guests 3 in Different Solvents at 25 °C
host
solvent (v:v)
3a (X ) PF6)
3b (X ) Cl)
3c (X ) CF3COO)
1
CH3CN:CH3OH (9:1)
CH3CN
1.9((0.2) × 102
3.2((0.3) × 102
8.6((0.9) × 102
1.3((0.2) × 103
1.9((0.7) × 103
5.5((0.5) × 102
1.4((0.1) × 103
3.7((0.3) × 103
7.1((2.6) × 103
1.3((0.3) × 104
1.2((0.1) × 102
0.9((0.2) × 102
1.3((0.1) × 102
4.2((0.3) × 102
7.8((1.3) × 102
1.0((0.2) × 103
4.7((0.3) × 102
1.2((0.1) × 103
2.5((0.3) × 104
1.0((0.1) × 105
2.2((0.1) × 105
a
CH3CN:CHCl3 (1:1)
CH3CN:CHCl3 (1:2)
CH3CN:CHCl3 (1:3)
CH3CN:CH3OH (9:1)
CH3CN
CH3CN:CHCl3 (1:1)
CH3CN:CHCl3 (1:2)
CH3CN:CHCl3 (1:3)
a
a
a
2
5.6((0.5) × 102
a
a
a
a
a Could not be determined due to the poor solubility of the salt in these solvents.
3-5). The high Ka value 2.2((0.1) × 105 M-1, for 2·3c in 1:3
acetonitrile:chloroform can be attributed to both the enhanced
binding affinity of the crown ether portion for the bipyridinium
cation via ion-pair recognition and the enhanced hydrogen
bonding strength in this lower polarity solvent system. Therefore,
the binding improvement induced by ion-pair recognition is not
only solvent polarity controlled but also anion controlled.
D. Solid State Structures of Complexes 2 ·3a, 2·3b,
and 2 ·3c. Suitable crystals of 2·3a, 2·3b, and 2·3c for single-
crystal X-ray analysis were all obtained by a vapor diffusion
method. The X-ray crystal structures (Figure 7) of complexes
2·3a, 2·3b, and 2·3c confirmed the ion-pair recognition
between 2 and 3 since the BMP32C10 moiety of 2 binds the
dicationic bipyridinium part of 3 and the two urea groups of 2
bind the two anions of 3 as we designed. All three 1:1 complexes
2·3a, 2·3b, and 2·3c are stabilized by hydrogen bonding
(Tables 2-4) between R-pyridinium hydrogens of 2 and
oxygens of 3 and face-to-face π-stacking interactions (Table 5)
between the two electron-rich phenylene rings of 2 and the two
electron-poor pyridinium rings of 3 in the solid state. None of
the methyl and ꢀ-pyridinium hydrogens are involved in hydro-
gen bonding between the host and guest. This is the same for
a previously reported complex based on a bis(m-phenylene)-
32-crown-10 derivative and 3a.11 What is interesting is that the
oxygen atoms of the two carbonyl groups of 2 form C-H· · ·O
hydrogen bonds (d, i, q, v, and a1 in Figure 7) with R-pyri-
dinium hydrogens of 3 in these three crystal structures, which
also stabilizes these three complexes in the solid state.
Both 2·3a and 2·3b are taco complexes, in which the
bipyridinium part of 3 is sandwiched between two phenylene
rings of 2, in the solid state (parts a and b of Figure 7). However,
a significant difference between the crystal structure of 2·3a
and that of 2·3b is that 2·3b forms a poly(taco complex)14
packing structure (part b of Figure 7) because one chloride anion
coordinates to two urea groups with a distorted tetrahedral
geometry.9 The poly(taco complex) packing structure formed
by strong N-H· · ·Cl hydrogen bonding contributed to the
stability of the crystals of 2·3b, which were stable in open air
for several months. What is surprising and more interesting is
that 2·3c is a pseudorotaxane, in which the dicationic bipyri-
dinium part of 3 threads through the cavity of 2, instead of a
taco complex in the solid state (part c of Figure 7). This is unique
since 2·3a, 2·3b, and all previously reported host-guest
complexes based on BMP32C10 and paraquat derivatives are
FIGURE 6. Determination of Ka of 2·3c in CH3CN:CHCl3 (1:3, v:v).
(a) The absorbance spectral changes of 2 (0.600 mM, 2.00 mL) upon
addition of 3c (2.00 mM) and (b) the absorbance intensity changes at
λ ) 376 nm upon addition of 3c (from 0 to 0.82 mM). The red solid
line was obtained from the nonlinear curve-fitting.
1·3c to 2·3c was 4.2 times in 9:1 acetonitrile:methanol, 8.2
times in acetonitrile, 59 times in 1:1 acetonitrile:chloroform,
127 times in 1:2 acetonitrile:chloroform, and 219 times in 1:3
acetonitrile:chloroform, respectively. Second, when the coun-
terions are different, the Ka increases are different. In 9:1
acetonitrile:methanol, the Ka increase is 1.9, 3.7, and 4.2 times
respectively from 1·3a to 2·3a, from 1·3b to 2·3b, and from
1·3c to 2·3c. In 1:1 acetonitrile:chloroform, the Ka increase is
3.3 and 59 times, respectively, from 1·3a to 2·3a and from
1·3c to 2·3c. In an even lower polarity solvent system, 1:3
acetonitrile:chloroform, the difference of the Ka increase is even
more apparent. The Ka value increased 5.8 and 219 times,
respectively, from 1·3a to 2·3a and from 1·3c to 2·3c. The
Ka increase difference for the paraquat guest salts reflects the
(14) Huang, F.; Fronczek, F. R.; Gibson, H. W. Chem. Commun. 2003, 1480–
1481.
(15) Here a hydrogen bond is thought to exist when the H · · ·O (F, Cl) distance
is less than the sum, 2.72 (2.67, 2.95) Å, of van der Waals radii (Bondi, A. J.
Phys. Chem. 1964, 68, 441-451) of the hydrogen atom and the acceptor O (F,
Cl) atom, and the C-H · · · O (F, Cl) angle is greater than 90°.3e
different binding strengths of the urea groups with the different
counteranions.9 This result is in accordance with the above-
1
mentioned changes of H NMR chemical shifts of the urea
protons after complexation with different paraquat salts (Figures
1326 J. Org. Chem. Vol. 74, No. 3, 2009

Anion-Controlled Ion-Pair Recognition of Paraquat
FIGURE 7. Ball-stick views and cartoon representations of the X-ray structures of 2·3a (a), 2·3b (b), and 2·3c (c). Color key: 2 is red, 3 is blue,
hydrogens are purple, oxygens are green, nitrogens are dark blue, phosphorus are yellow, fluorins are light blue, and chlorides are black. Solvent
molecules and hydrogens except the ones involved in hydrogen bonding between 2 and 3 were omitted for clarity.
TABLE 2. Hydrogen-Bond Parameters for 2 ·3a15
parameters
a
b
c
d
e
f
g
h
i
j
k
C(N)· · ·O(F) distances (Å)
H· · ·O(F) distances (Å)
C(N)-H· · ·O(F) angles (deg)
3.19
2.37
159
3.22
2.43
154
3.00
2.25
143
3.16
2.42
136
3.30
2.45
152
3.19
2.46
135
3.39
2.57
148
3.31
2.69
125
3.20
2.40
144
3.21
2.35
171
3.09
2.25
166
TABLE 3. Hydrogen-Bond Parameters for 2 ·3b15
parameters
l
m
n
o
p
q
r
s
C(N)· · ·O(Cl) distances (Å)
H· · ·O(Cl) distances (Å)
C(N)-H· · ·O(Cl) angles (deg)
3.29
2.50
163
3.37
2.51
145
3.63
2.71
170
3.17
2.44
136
3.33
2.53
145
3.11
2.49
124
3.31
2.48
165
3.50
2.71
153
TABLE 4. Hydrogen-Bond Parameters for 2 ·3c15
parameters
t
u
v
w
x
y
z
a1
b1
c1
C(N)· · ·O distances (Å)
H· · ·O distances (Å)
C(N)-H· · ·O angles (deg)
2.91
2.08
162
2.84
2.00
157
3.16
2.39
140
3.00
2.39
122
3.19
2.31
159
3.19
2.31
159
3.00
2.39
122
3.16
2.39
140
2.91
2.08
162
2.84
2.00
157
TABLE 5. Selected Distances and Angles for 2 ·3a, 2 ·3b and 2 ·3c
parameters
2·3a
2 ·3b
2 ·3c
face-to-face π-stacking centroid-centroid distances (Å)
3.53, 3.59
7.5, 3.7
7.59
20
4.28
3.56, 3.69
5.6, 3.1
7.45
18
4.29
3.66, 3.66
face-to-face π-stacking ring plane/ring plane inclinations (deg)
centroid-centroid distance (Å) between two phenylene rings of 2
dihedral angle (deg) between two phenylene rings of 2
centroid-centroid distance (Å) between two pyridinium rings of 3
dihedral angle (deg) between two pyridinium rings of 3
7.0, 7.0
7.61
0
4.27
0
28
22
taco complexes in the solid state.7f-h,11,14 Possibly due to the
difference in the host-guest complexation geometry of 2·3c
compared with 2·3a and 2·3b, both the dihedral angle between
the two phenylene rings of 2 and the dihedral angle between
the two pyridinium rings of 3 are 0°, very different from the
corresponding values (20° and 28° or 18° and 22°) for these
two angles in the case of 2·3a or 2·3b (Table 5). Therefore,
the complexation motif for incorporation of paraquat guest 3
into heteroditopic host 2 is anion controlled in the solid state.
is controlled by not only the solvent polarity but also the nature
of the anion. This enables us to control the host-guest binding
strength by simply changing anions. Furthermore, it was found
that the complexation motif relating to the geometry of inclusion
of paraquat guest 3 in the cavity of heteroditopic host 2 is anion
controlled in the solid state. This is a new way to control the
host-guest complexation geometry and should be useful in the
future fabrication of molecular machines and storage materials.
Experimental Section
Conclusions
N,N′-Dimethyl-4,4′-bipyridinium trifluoroacetate (3c). A mix-
ture of 4,4′-bipyridine (1.60 g, 10.0 mmol) and methyl iodide (1.70
g, 12.0 mmol) was refluxed in CH3CN for 12 h and a red solid
was precipitated. The red solid was filtered and washed with CH3CN
and dried. The dried N,N′-dimethyl-4,4′-bipyridinium iodide (220
The complexation of divalent salts such as paraquat by crown
ethers can be greatly improved (a Ka increase up to 219 times
was observed here) by the introduction of ion-pair recognition
as a means of also binding the counterions. The improvement
J. Org. Chem. Vol. 74, No. 3, 2009 1327

Zhu et al.
mg, 0.500 mmol) was dissolved in deionized water (2.00 mL) and
an aqueous solution (2.00 mL) containing silver trifluoroacetate (440
mg, 1.00 mmol) was slowly added with vigorously stirring. The
resulting mixture was centrifugated and the supernatant liquid was
isolated. After the solvent was evaporated under reduced pressure,
a white solid was obtained. This crude product was redissolved
into CH3CN and precipitated by adding isopropyl ether, affording
the pure trifluoroacetate salt 3c (165 mg, 80%). Mp 185-190 °C
4H), 6.31 (t, J ) 2.4 Hz, 2H), 4.02 (t, J ) 4.8 Hz, 8H), 3.79 (t, J
) 4.8 Hz, 8H), 3.71 (s, 4H), 3.62-3.69 (m, 16H). 13C NMR (100
MHz, CDCl3, 22 °C) δ 159.7, 145.1, 105.6, 99.6, 70.5, 69.4, 67.2,
46.1. Low-resolution ESI-MS: m/z 595.3 (100%) [6 + H]+. HR
ESI-MS m/z calcd for [M + H]+ C30H47N2O10 595.3225, found
595.3222, error 0.5 ppm.
Bis[5-(phenylureidomethylene)-m-phenylene]-32-crown-10
(2). A solution of 590 mg (1.00 mmol) of 6 and 240 mg (2.00
mmol) of phenylisocyanate in 30.0 mL of CHCl3 was stirred at
room temperature for 12 h under N2 atmosphere. The reaction
mixture was added with 10 mL of 1.00 M HCl aqueous solution
and the organic layer was then washed with 10 mL of brine twice.
After drying over Na2SO4, the solvent was removed by a rotary
evaporator to afford the crude product, which was recrystallized
from acetone to give 2 as a white solid (790 mg, 95%). Mp
1
dec. H NMR (400 MHz, CD3CN, 22 °C) δ 9.01 (d, J ) 6.4 Hz,
4H), 8.54 (d, J ) 6.4 Hz, 4H), 4.43 (s, 6H). Anal. Calcd for
C16H14N2O4F6: C, 46.61; H, 3.42; N, 6.79. Found: C, 46.50; H,
3.40; N, 6.82.
Bis(5-phthalimidomethyl-m-phenylene)-32-crown-10 (5). Com-
pound 5 was synthesized according to a similar method for
monofunctionalization of phenyl crown ethers.12 A solution of 410
(3.61 g, 5.00 mmol), potassium phthalimide (2.00 g, 10.8 mmol),
and DMF (50.0 mL) was held at 90 °C for 24 h and then cooled to
room temperature. The solvent was evaporated under reduced
pressure. The residue was dissolved in 200 mL of CH2Cl2 and
washed with 100 mL of water twice. The organic layer was dried
over anhydrous Na2SO4 and evaporated in vacum to afford the crude
product, which was isolated by flash column chromatography with
the CH2Cl2/CH3OH (v:v ) 20:1) as the eluent to afford 5 as a white
solid (3.90 g, 91%). Mp 144-145 °C. 1H NMR (400 MHz, CDCl3,
22 °C) δ 7.81 (m, 4H), 7.68 (m, 4H), 6.52 (d, J ) 2.4 Hz, 4H),
6.33 (t, J ) 2.4 Hz, 2H), 4.71 (s, 4H), 4.00 (t, J ) 4.4 Hz, 8H),
3.78 (t, J ) 4.4 Hz, 8H), 3.64-3.68 (m, 16H). 13C NMR (100 MHz,
CDCl3, 22 °C) δ 168.0, 160.0, 138.3, 133.9, 132.0, 123.3, 107.2,
100.7, 70.8, 70.8, 69.5, 67.5, 41.5. Low-resolution ESI-MS m/z
872.7 (100%) [5 + NH4]+ and 877.7 (45%) [5 + Na]+. Anal. Calcd
for C46H50N2O14: C, 64.63; H, 5.90; N, 3.28. Found: C, 64.45; H,
5.93; N, 3.27.
1
202-203 °C. H NMR (400 MHz, CD3CN, 22 °C) δ (ppm) 7.58
(s, 2H), 7.38 (d, J ) 8.0 Hz, 4H), 7.23 (t, J ) 8.0 Hz, 4H), 6.95
(t, J ) 7.2 Hz, 2H), 6.41 (d, J ) 1.6 Hz, 4H), 6.28 (s, 2H), 5.87
(t, J ) 5.2 Hz, 2H), 4.21 (d, J ) 5.6 Hz, 4H), 3.98 (t, J ) 4.8 Hz,
8H), 3.72 (t, J ) 4.8 Hz, 8H), 3.56-3.60 (m, 16H). 13C NMR (100
MHz, CDCl3, 22 °C) δ 207.1, 159.8, 156.3, 153.7, 141.2, 139.4,
138.9, 128.8, 122.8, 122.4, 119.5, 119.2, 106.1, 100.4, 70.5, 70.4,
69.8, 67.3, 43.9. Low-resolution ESI-MS m/z 833.5 (71%) [2 +
H]+ and 855.4 (100%) [2 + Na]+. Anal. Calcd for C46H50N2O14:
C, 63.45; H, 6.78; N, 6.73. Found: C, 63.46; H, 6.74; N, 6.73.
Acknowledgment. This work was supported by the National
Natural Science Foundation of China (20604020 and 20774086).
We thank Professor Wanzhi Chen from Zhejiang University for
his kind assistance with X-ray crystallography.
Note Added after ASAP Publication. The expression
[2·3-X]+ was incorrectly printed as [2·3-X]2+ in section B
in the version published ASAP January 6, 2009; the corrected
version was published ASAP January 8, 2009.
Bis(5-aminomethyl-m-phenylene)-32-crown-10 (6). Compound
6 was synthesized according to a similar method for monofunc-
tionalization of phenyl crown ethers.12 A solution of 5 (2.60 g,
3.00 mmol), hydrazine monohydrate (0.500 mL, 8.50 mmol), and
methanol (10.0 mL) was refluxed for 12 h, cooled, and concentrated
by rotary evaporation. The mixture was filtered and the solid was
washed with 5 mL of methanol twice. The combined filtrate was
neutralized to pH >12 with 2.00 M NaOH and extracted with
CHCl3. The combined extracts were dried over anhydrous Na2SO4
and evaporated in vacuo to afford 6 (1.60 g, 89%) as a light yellow
Supporting Information Available: Determination of as-
sociation constants, 1H and 13C NMR spectra, electrospray
ionization mass spectra, X-ray crystallographic files (CIF) for
2·3a, 2·3b, and 2·3c, and other materials. This material is
available free of charge via the Internet at http://pubs.acs.org.
1
oil. H NMR (400 MHz, CDCl3, 22 °C) δ 6.42 (d, J ) 2.4 Hz,
JO802683D
1328 J. Org. Chem. Vol. 74, No. 3, 2009