Selective recognition of an alkali halide contact ion-pair [1]

Full text of DOI:10.1021/ja0156082

J. Am. Chem. Soc. 2001, 123, 5847-5848
5847
Table 1. Association Constants, K (M-1), in DMSO-d6 at T ) 295
Selective Recognition of an Alkali Halide Contact
Ion-Pair
Ka
b
-
c
+
c
+
KCl
KNa
KK
2 + Na+
2 + K+
2
2 + Cl-
2
2 + Cl-
Joseph M. Mahoney, Alicia M. Beatty, and Bradley D. Smith*
2
35
50
460
5
25
8
340
Department of Chemistry and Biochemistry
a Association constants are the average of all receptor protons which
exhibited significant complexation-induced shifts; initially [2] ) 10
mM; uncertainty (15%. b 2/Cl- association constant in the presence
or absence of 1 molar equiv of metal tetraphenylborate. c 2/M+
association constant in the presence or absence of 1 molar equiv of
tetrabutylammonium chloride.
UniVersity of Notre Dame, Notre Dame, Indiana 46556-5670
ReceiVed January 30, 2001
ReVised Manuscript ReceiVed April 25, 2001
For more than 30 years there has been an active and continued
effort to develop synthetic receptors for anions and cations in
organic solvents.1 We2 and others3 have shown that if both of
the counterions in a target salt have localized charges then the
consequent ion-pairing of the salt can dramatically lower receptor/
ion binding affinities and alter binding selectivities. One way to
counter this problem is to develop ditopic receptors that can
simultaneously bind both of the counterions.4 Recently, we
investigated the salt binding properties of receptor 1 and found
that the presence of 1 molar equiv of Na+ or K+ ion increases
the 1/Cl- association constant by slightly less than ten.5 An X-ray
crystal structure showed that receptor 1 binds NaCl as a solvent
separated ion-pair. We felt that the binding cooperativity would
be improved if the salt were bound to the receptor as a contact
ion-pair. Thus, we designed macrobicyclic receptor 2 as a salt-
binding analogue of 1 but with a smaller distance between the
anion and cation binding sites.6 Using NMR spectroscopy and
X-ray crystallography we find that 2 is the first example of a
ditopic salt-receptor that binds a contact ion-pair in solution more
strongly than either of the free ions.
complex is sufficiently stable to survive column chromatography
using silica gel and weakly polar solvents. A quantitative
1
evaluation of its salt binding ability was obtained by H NMR
titration experiments in highly polar DMSO-d6. Cl- affinities were
derived by adding aliquots of tetrabutylammonium chloride to a
solution of 2 in the absence and presence of 1 molar equiv of
potassium or sodium tetraphenylborate. Receptor 2 has negligible
affinity for the diffuse tetrabutylammonium cation and tetra-
phenylborate anion, thus they are simply “spectator ions”. The
complex-induced changes in chemical shift were consistent with
the Cl- forming hydrogen bonds with the isophthalamide NH
residues in 2. K+ and Na+ affinities were determined by adding
aliquots of the appropriate metal tetraphenylborate to a solution
of 2 in the absence and presence of 1 molar equiv of tetrabutyl-
ammonium chloride. The complex-induced changes in chemical
shift were consistent with the metal cations being encapsulated
by the diazacrown ring. In each case, association constants were
obtained by fitting the titration isotherms to a 1:1 binding model
using an iterative computer method.7 As shown in Table 1,
receptor 2 has a weak affinity for Cl- in DMSO-d6.8 The 2/Cl-
association constant is hardly affected by the presence of Na+,
but it is increased more than 10-fold by the presence of K+.9 In
terms of cation binding, the weak affinities receptor 2 has for
Na+ and K+ are increased 5- and 40-fold, respectively, by the
presence of Cl-. The results in Table 1 suggest that ditopic
receptor 2 binds ion-paired potassium chloride more tightly than
either free K+ or Cl-. Significantly higher binding enhancements
were obtained in the less polar solvent mixture of CDCl3:DMSO-
d6 (85:15). For example, the 2/Cl- association constant was
increased from 80 M-1 to 2.5 × 104 M-1 by the presence of 1
molar equiv of potassium tetraphenylborate.10 This remarkable
300-fold enhancement in association constant is considerably
higher than that observed with most, if not all, other salt binding
systems.4,5
The macrobicycle 2 was prepared in three steps from com-
mercially available materials. Receptor 2 is able to dissolve 1
molar equiv of KCl in chloroform solution and the resulting
(1) (a) Schneider, H. J.; Yatsimirski, A. Principles and Methods in
Supramolecular Chemistry; Wiley: Somerset, NJ, 2000. (b) Steed, J. W.;
Atwood, J. L. Supramolecular Chemistry; Wiley: New York, 2000.
(2) Shukla, R.; Kida, T.; Smith, B. D. Org. Lett. 2000, 2, 3039-3248.
(3) (a) Olsher, U.; Hankins, M. G.; Kim, T. D.; Bartsch, R. A. J. Am. Chem.
Soc. 1993, 115, 3370-3371. Olsher, U.; Feinberg, H.; Frolow, F.; Shoham,
G. Pure Appl. Chem. 1996, 68, 1195-199. (b) Lamb, J. D. In ComprehensiVe
Supramolecular Chemistry; Atwood, J. L., Davies, J. E. D., MacNicol, D.
D., Vo¨gtle, F., Lehn, J.-M., Gokel, G. W., Eds.; Pergamon: Oxford, 1996;
Vol. 10, p 90. (c) Moyer, B. A. In ComprehensiVe Supramolecular Chemistry;
Atwood, J. L., Davies, J. E. D., MacNicol, D. D., Vo¨gtle, F., Lehn, J.-M.,
Gokel, G. W., Eds.; Pergamon: Oxford, 1996; Vol. 1, p 401. (d) Danil de
Namor, A.; Ng, J. C. Y.; Llosa Tanco, M. A.; Salomon, M. J. Phys. Chem.
1996, 100, 11485-11491. (e) Arnecke, R.; Bo¨hmer, V.; Cacciapaglia, R.;
Dalla Cort, A.; Mandolini, L. Tetrahedron 1997, 53, 4901-4908. (f) Bartoli,
S.; Roelens, S. J. Am. Chem. Soc. 1999, 121, 11908-11909. (g) Bo¨hmer, V.;
Cort, A. D.; Mandolini, L. J. Org. Chem. 2001, 66, 1900-1902.
(4) Recent reviews that discuss salt-binding receptors: (a) Beer, P. D.; Gale,
P. A. Angew. Chem., Int. Ed. 2001, 40, 486-516. (b) Antonisse, M. M. G.;
Reinhoudt, D. N. J. Chem. Soc., Chem. Commun. 1998, 443-448. (c) Kimura,
E.; Koike, T. J. Chem. Soc., Chem. Commun. 1998, 1495-1500. (d) Reference
5 and citations therein.
Further insight into the binding process was gained from X-ray
crystallography. Single crystals of 2 were obtained by slowly
evaporating an aqueous methanol solution and X-ray analysis
produced the crystal structure shown in Figure 1a. The structure6
helps explain why 2 can bind ion-pairs better than isolated ions.
For example, the cavity of the macrobicycle contains a network
of hydrogen-bonded solvent molecules that inhibit guest access.
A water bridges the diazacrown and the anion binding site
(7) Hughes, M. P.; Smith, B. D. J. Org. Chem. 1997, 62, 4492-4501.
(8) The 2/Cl- and 2/Na+ association constants in DMSO are similar to
those observed with monotopic control compounds such as an acyclic
isophthalamide5 and 1,10-diaza-18-crown-6 (Shamsipur, M.; Popov, A. Inorg.
Chim. Acta 1980, 43, 243-247), respectively.
(9) While we do not know the exact distribution of free ions, ion-pairs,
aggregated ion-pairs, and receptor-bound ions,2 the data in Table 1 are useful
in a comparative sense in that they show that K+ increases 2/Cl- affinity
more than the same amount of Na+ (and vice versa).
(5) Deetz, M. J.; Shang, M.; Smith, B. D. J. Am. Chem. Soc. 2000, 122,
6201-6207.
(6) For a related but subtly different structure, see: Flack, S. S.; Chaumette,
J.-L.; Kilburn, J. D.; Langley, G. J.; Webster, M. Chem. Commun. 1993, 399-
400.
(10) The 2/Cl- association constant could not be determined in the presence
of 1 molar equiv of sodium tetraphenylborate because of precipitation
problems. Also the Na+ and K+ association constants in CDCl3:DMSO-d6
(85:15) could not be determined due to the limited solubility of sodium and
potassium tetraphenylborate.
10.1021/ja0156082 CCC: $20.00 © 2001 American Chemical Society
Published on Web 05/26/2001

5848 J. Am. Chem. Soc., Vol. 123, No. 24, 2001
Communications to the Editor
complexes, the KCl is bound as a contact ion-pair but the K-Cl
distances of 2.989(2) and 3.081(2) Å are measurably different.11
One of the structures is depicted in Figure 1b. It shows that the
K+ is in its expected position inside the diazacrown (average K-O
distance is 2.77 Å), but because of confomational contraints forced
by the bicyclic structure, the K-N distances are unusually long
(average K-N distance is 3.33 Å).12,13 As expected, the bound
Cl- is hydrogen bonded to the isophthalamide NH residues.14
An explanation of why K+ enhances 2/Cl- binding better than
Na+ is provided by the X-ray structure of the 2‚NaCl complex
(Figure 1c). The diazacrown alters its conformation and reduces
its effective cavity size to accommodate the smaller Na+ ion which
is only coordinated by the four crown oxygens (average Na-O
distance is 2.45 Å) and one of the two nitrogens (one Na-N
distance is 3.15 Å whereas the other is 3.96 Å).12 The average
Cl-N distance is 3.35 Å14 and the Na-Cl distance is 2.702(2)
Å.11 In the case of the 2‚NaCl complex, the average distance from
the four diazacrown oxygens to the Cl- is 4.20 Å, which is
significantly closer than the 4.71 Å observed in the 2‚KCl
complex. This appears to be the major reason K+ enhances 2/Cl-
binding better than Na+. After binding a K+ ion, receptor 2 is
able to nicely accommodate a Cl- and form a favorable contact-
ion pair. However, in the case of Na+, the advantage of forming
a contact-ion pair is offset by increased ion-dipole repulsions
between the Cl- and the diazacrown oxygens that closely
coordinate the Na+. This explanation is consistent with the
observation of Gokel that a related two-armed diaza-18-crown-6
lariat ether with aromatic side-chains forms a K+-arene interac-
tion but not a Na+-arene interaction.13
In summary, we report the first unambiguous example of a
ditopic salt receptor that binds alkali halides as their contact ion-
pairs. This produces some subtle recognition properties apparently
due to differences in alkali cation coordination geometry. For
example, K+ strongly enhances 2/Cl- affinity whereas the more
closely coordinated Na+ has little effect. This result is in contrast
to the case of receptor 1 that binds MCl as a solvent separated
ion-pair. In this latter case, both Na+ and K+ have the same
moderate enhancing effect on receptor/Cl- affinity.5
Acknowledgment. This paper is dedicated to Professor L. M. Jackman
on the occasion of his 75th birthday. This work was supported by the
National Science Foundation.
Supporting Information Available: Receptor synthesis and titration
data (PDF) and X-ray crystal data in CIF format. This material is available
free of charge via the Internet at http://pubs.acs.org.
JA0156082
(11) Our observed K-Cl distances of 2.989(2) and 3.081(2) Å are shorter
than the 3.14 Å seen in crystalline KCl, and our observed Na-Cl distance of
2.702(2) Å is also shorter than the 2.81 Å seen in crystalline NaCl. Wells, A.
F. Structural Inorganic Chemistry; Oxford Press: Oxford, 1984.
(12) The typical distances for 1,10-diaza-18-crown-6 complexes are the
following: Na-O, ∼2.45 Å; K-O, ∼2.75 Å; Na-N, 2.5-3.0 Å; K-N, 3.0-
3.2 Å. De Wall, S. L.; Meadows, E. S.; Barbour, L. J.; Gokel, G. W. Proc.
Natl. Acad. Sci. U.S.A. 2000, 97, 6271-6276. De Wall, S. L.; Meadows, E.
S.; Barbour, L. J.; Gokel, G. W. J. Am. Chem. Soc. 1999, 121, 5613-5614.
De Wall, S. L.; Meadows, E. S.; Barbour, L. J.; Gokel, G. W. Chem. Commun.
1999, 1553-1554. Meadows, E. S.; De Wall, S. L.; Barbour, L. J.; Gokel, G.
W. Chem. Commun. 1999, 1555-1556. Gandour, R. D.; Fronczek, F. R.;
Gatto, V. J.; Minganti, C.; Scultz, R. A.; White, B. D.; Arnold, K. A.;
Mazzocchi, A. D.; Miller, S. R.; Gokel, G. W. J. Am. Chem. Soc. 1986, 108,
4078-4088.
Figure 1. X-ray crystal structures showing 50% probability ellipsoids
and no CH residues: (a) receptor 2 with a water and methanol in the
cavity, (b) one of the two 2‚KCl structures found in the unit cell, and (c)
2‚NaCl.
contains either a methanol molecule (60% occupancy and shown
in Figure 1a) or two bridging waters (40% occupancy, not shown).
It appears that binding of a cation or an anion displaces any
trapped solvent molecules so they do not inhibit binding of the
second counterion.
Single crystals of the 2‚KCl complex were obtained by evap-
orating an ethyl acetate solution of 2 saturated with KCl. X-ray
analysis uncovered two independent but structurally similar
complexes in the unit cell (see Supporting Information). In both
(13) De Wall, S. L.; Barbour, L. J.; Gokel, G. W. J. Am. Chem. Soc. 1999,
121, 8405-8406.
(14) The average of the four Cl-N distances in both 2‚KCl complexes in
the unit cell is 3.30 Å, which is close to the 3.35 Å average seen in the 2‚
NaCl complex and the 3.33 Å average previously reported for 1‚NaCl.5