Tricyclic host for linear anions

Article abstract of DOI:10.1021/ic1013297

A tricyclic host for anions consisting of two tetraamide monocycles attached by two ethylene chains was designed and synthesized. Structural and binding results indicate that the receptor is selective for linear triatomic anions. Crystallographic data for two hydrated free bases, along with FHF ^-, N₃^-, and SO₄^2- complexes indicate that there are at least two preferred gross conformations for the host, one of which possesses pseudo-D₂ symmetry and the other pseudo-C_2h symmetry. Both FHF^- and N₃ ^- are encapsulated in the pseudo-D₂ symmetric complex, bridging the two tetraamido macrocyclic halves. The pseudo-C_2h octahydrate structure shows an ice-like H-bonded (H₂O)₆ array of water molecules embedded in the host cavity. The SO₄ ^2- structure has a nearly superimposable host conformation to the octahydrate but with the SO₄^2- anions lying outside the host. Binding studies in DMSO-d₆ indicate selectivity for FHF ^-, with lesser affinity for other inorganic anions.

Full text of DOI:10.1021/ic1013297

Inorg. Chem. 2010, 49, 8629–8636 8629
DOI: 10.1021/ic1013297
Tricyclic Host for Linear Anions
Sung Ok Kang, Victor W. Day, and Kristin Bowman-James*
Department of Chemistry, University of Kansas, Lawrence, Kansas 66045
Received July 2, 2010
A tricyclic host for anions consisting of two tetraamide monocycles attached by two ethylene chains was designed and
synthesized. Structural and binding results indicate that the receptor is selective for linear triatomic anions. Crystallo-
graphic data for two hydrated free bases, along with FHF-, N3-, and SO42- complexes indicate that there are at least
two preferred gross conformations for the host, one of which possesses pseudo-D2 symmetry and the other pseudo-
C2h symmetry. Both FHF- and N3- are encapsulated in the pseudo-D2 symmetric complex, bridging the two tetra-
amido macrocyclic halves. The pseudo-C2h octahydrate structure shows an ice-like H-bonded (H2O)6 array of water
molecules embedded in the host cavity. The SO42- structure has a nearly superimposable host conformation to the
octahydrate but with the SO42- anions lying outside the host. Binding studies in DMSO-d6 indicate selectivity for FHF-,
with lesser affinity for other inorganic anions.
Introduction
differ in shape and size. Spherical anions were early targets of
anion researchers,4 and even more recently F- is still of great
interest.5 However, the first example of a structural report of
an encapsulated multiatomic anion with more complex
In the past decade, anion coordination chemistry has been
established as an independent field,1-3 and the wide selection
of ligand sizes, shapes, and H-bond donor groups is impres-
sive. In part, this is because host design is a key factor to
targeting H-bond directionality preferences for anions that
H-bonding needs was for the triatomic N3 ion.6 The host
-
in this case was a relatively simple bicyclic azacryptand, bis-
tren, reported by Lehn and co-workers. Because of its cylind-
rical shape, bis-tren was considered to be a perfect fit for
linear anions, suggesting that FHF- might also be a candi-
date for encapsulation. Since then other hosts for N3- have
been reported.7 However, despite the reported physical
evidence for FHF- encapsulation in solution,8 no crystal-
lographic confirmation of sequestration had been obtained
for FHF- until our earlier communication.9
*To whom correspondence should be addressed. E-mail: kbjames@
ku.edu.
(1) (a) Supramolecular Chemistry of Anions; Bianchi, A.; Bowman-James,
~
K.; García-Espana, E.; Eds.; Wiley-VCH: New York, 1997. (b) Sessler, J. L.; Gale,
P. A.; Cho, W. S. Anion Receptor Chemistry; Royal Society of Chemistry:
Cambridge, UK, 2006.
(2) (a) Beer, P. D.; Smith, D. K. Prog. Inorg. Chem. 1997, 46, 1–96.
(b) Schmidtchen, F. P.; Berger, M. Chem. Rev. 1997, 97, 1609–1646. (c) Gale,
P. A. Coord. Chem. Rev. 2000, 199, 181–233. (d) Beer, P. D.; Gale, P. A. Angew.
Chem., Int. Ed. 2001, 40, 486–516. (e) McKee, V.; Nelson, J.; Town, R. M.
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2003, 240, 57–75. (b) Bowman-James, K. Acc. Chem. Res. 2005, 38, 671–678.
(c) Kang, S. O.; Begum, R. A.; Bowman-James, K. Angew. Chem., Int. Ed. 2006,
45, 7882–7894. (d) Kang, S. O.; Hossain, M. A.; Bowman-James, K. Coord.
Chem. Rev. 2006, 250, 3038–3052.
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2432. (b) Graf, E.; Lehn, J.-M. J. Am. Chem. Soc. 1975, 97, 5022–5024. (c) Graf,
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In a systematic study over the past decade of the influence
of dimensionality on anion binding, we have designed a series
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Powell, D.; Bowman-James, K. J. Am. Chem. Soc. 2004, 126, 12272–12273.
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Kang, S. O.; Day, V. W.; Bowman-James, K. J. Org. Chem. 2010, 75, 277–283.
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M.-J. R.; Ugozzoli, F. Angew. Chem., Int. Ed. 2006, 45, 6920–6924. (b) Kim,
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r
2010 American Chemical Society
Published on Web 08/25/2010
pubs.acs.org/IC

8630 Inorganic Chemistry, Vol. 49, No. 18, 2010
Scheme 1. Synthesis of Tricycle 1
Kang et al.
of mixed amide/amine-containing hosts of expanding com-
plexity. Monocycles appear to be selective for oxo acids,10
while bicyclic cryptands show higher affinities for halides,
especially F-.11 By connecting two monocycles with an
ethylene bridge, the tricycle 1 materialized. Only a limited
number of higher-order multicyclic amide anion hosts have
been reported12-16 even though these more complex hosts
show great potential for anion coordination. Binding proper-
ties of the new tricycle 1 indicated a preference for the small
triatomic FHF- ion, and crystallographic studies indicated
encapsulation between the two macrocyclic units.9 Subse-
quent experimentation led to the isolation of an almost
using selective protection and deprotection techniques
(Scheme 1) since the condensation reaction of diethylene-
triamine without the central amine protection did not give
the desired macrocycle. The terminal amines of diethyle-
netriamine 2 were protected with phthaloyl (Pht) groups,
followed by protection of the central secondary amine
with a tert-butoxycarbonyl (Boc) group. Deprotection of
the terminal amines with hydrazine gave the Boc-pro-
tected triamine 5 which yielded 6 upon condensation with
an equimolar amount of pyridine-2,6-dicarbonyl chloride
in the presence of Et3N as a base. This key macrocycliza-
tion reaction also yielded 1x1 and 3x3 adducts as minor
products. Better yields of the desired product were ob-
tained with high dilution conditions. The deprotected
macrocycle 7 resulted after 6 was reacted with trifluoro-
acetic acid. The tricycle 1 was obtained in 30% yield by
coupling two of the macromonocycles, 7, at the unpro-
tected amine sites using dibromoethane. The overall yield
for the entire sequence was 2.8%.
-
identical structure of an encapsulated N3 ion. Crystal
structure determination and solution chemistry are reported
herein for the new anion host, the tricyclic receptor 1, and its
anion complexes.
Results and Discussion
Synthesis. The tricycle was synthesized by bridging two
tetraamido macrocycles with two ethylene spacers. The
monocycle 7, the key precursor to 1, was synthesized
Structural Considerations. Two different preferred con-
formations were found for 1 (one with pseudo-D2 symmetry
and one with pseudo-C2h symmetry). In the hexahydrated
-
(9) Kang, S. O.; Powell, D.; Day, V. W.; Bowman-James, K. Angew.
Chem., Int. Ed. 2006, 45, 1921–1925.
(10) (a) Hossain, M. A.; Llinares, J. M.; Powell, D.; Bowman-James, K.
Inorg. Chem. 2001, 40, 2936–2937. (b) Hossain, M. A.; Kang, S. O.; Powell, D.;
Bowman-James, K. Inorg. Chem. 2003, 42, 1397–1399.
free base and the FHF- and N3 complexes, the two
folded macrocycles were rotated from each other by 90ꢀ
about a pseudo-S4 axis running through the center of the
two monocycles. However, the integrity of this axis is
(11) (a) Kang, S. O.; Llinares, J. M.; Powell, D.; VanderVelde, D.;
Bowman-James, K. J. Am. Chem. Soc. 2003, 125, 10152–10153. (b) Kang,
S. O.; VanderVelde, D.; Powell, D.; Bowman-James, K. J. Am. Chem. Soc. 2004,
126, 12272–12273. (c) Kang, S. O.; Powell, D.; Bowman-James, K. J. Am.
Chem. Soc. 2005, 127, 13478–13479.
(12) Pascal, R. A.; Spergel, J.; Engen, D. V. Tetrahedron Lett. 1986, 27,
4099–4102.
(13) (a) Pieters, R. J.; Diederich, F. J. Chem. Soc. Chem. Commun. 1996,
2255–2256. (b) Bucher, C.; Zimmerman, R. S.; Lynch, V.; Sessler, J. L. J. Am.
Chem. Soc. 2001, 123, 9716–9717.
(14) Bisson, A. P.; Lynch, V. M.; Monahan, M. C.; Anslyn, E. V. Angew.
Chem., Int. Ed. 1997, 36, 2340–2342.
(15) Kang, S. O.; Day, V. W.; Bowman-James, K. Org. Lett. 2008, 10,
2677–2680.
(16) (a) Davis, A. P.; Wareham, R. S. Angew. Chem., Int. Ed. 1998, 37,
2270–2273. (b) Lecollinet, G.; Dominey, A. P.; Velasco, T.; Davis, A. P. Angew.
Chem., Int. Ed. 2002, 41, 4093–4096. (c) Klein, E.; Crump, M. P.; Davis, A. P.
Angew. Chem., Int. Ed. 2005, 44, 298–302. (d) Klein, E.; Ferrand, Y.; Auty,
E. K.; Davis, A. P. Chem. Commun. 2007, 2390–2392.
broken in the free base 1 6H2O because of intramolecular
3
CdO HN H-bonds. For the octahydrated free base
3 3 3
2-
and the bis-SO4 complex, pseudo-C2h symmetry was
observed for the once again folded macrocycles. These
two conformational classes are discussed separately be-
low. Selected H-bond distances are provided in Tables 1
and 2, and perspective views of the hosts are shown in
Figures 1 and 2, for the pseudo D2 and C2h symmetry classes,
respectively.
Pseudo-D2 Structures (S4-like Symmetry): [1] 6H2O,
3
[1(FHF-)], and [1(N3-)]. The prototype host structure for
the pseudo-D2 conformation is the hexahydrated free base
structure, [1] 6H2O, which crystallized in the monoclinic
3
space group C2/c. The N3- complex, [nBu4Nþ][1(N3-)]
3
3H2O, crystallized in the monoclinic space group C21,

Article
Inorganic Chemistry, Vol. 49, No. 18, 2010 8631
Table 1. Selected H-Bonding Distances for [1], [1(N3-)], and [1(FHF-)]a
D-H
A
d(D A)
3 3 3
—(DHA)
D-H
A
d(D A)
3 3 3
—(DHA)
3 3 3
3 3 3
[1] 6H2O
3
N(4)-H(4) N(1)
3 3 3
2.814(2)
2.710(2)
2.689(1)
104(1)
108(1)
111(2)
N(19)-H(19) N(22)
3 3 3
2.576(1)
2.905(1)
115(2)
159(2)
N(4)-H(4) N(7)
N(13)-H(13) O(4)
3 3 3
3 3 3
N(19)-H(19) N(16)
3 3 3
[1(N3-)][nBu4N]þ 3H2O
3
N(4)-H(4) N(1)
2.842(4)
2.771(5)
2.883(5)
2.760(5)
2.854(4)
2.772(5)
102
105
101
104
102
104
N(51)-H(51) N(48)
2.944(5)
2.748(5)
2.895(5)
2.873(5)
2.906(5)
2.854(5)
100
105
143
144
145
149
3 3 3
3 3 3
N(4)-H(4) N(7)
N(51)-H(51) N(54)
3 3 3
3 3 3
N(19)-H(19) N(16)
N(13)-H(13) N(1A)
3 3 3
3 3 3
N(19)-H(19) N(22)
N(28)-H(28) N(1A)
3 3 3
3 3 3
N(36)-H(36) N(33)
N(45)-H(45) N(3A)
3 3 3
3 3 3
N(36)-H(36) N(39)
N(60)-H(60) N(3A)
3 3 3
3 3 3
[1(FHF-)][nBu4N]þ 3H2Ob
3
N(4)-H(4) N(1)
2.839(2)
2.755(3)
2.896(4)
2.734(4)
98(2)
111(2)
114(4)
102(3)
N(13)-H(13) F(1)
2.754(3)
2.724(3)
2.475(4)
155(3)
154(2)
168(4)
3 3 3
3 3 3
N(4)-H(4) N(7)
N(28)-H(28) F(1)
3 3 3
3 3 3
N(19)-H(19) N(16)
F(1)-H(1) F(10)#1
3 3 3
3 3 3
N(19)-H(19) N(22)
3 3 3
aIn this table and the subsequent Table 2, standard deviations are only reported for H-bond angles where the positional parameters of the hydrogen
atom were refined. bSymmetry transformations used to generate equivalent atoms: a1: x, -y þ 1, -z þ 1.
Table 2. Selected H-Bonding Distances for [1(H2O)6] and [H41(SO4)2(H2O)2]
D-H
A
d(D A)
3 3 3
—(DHA)
[1(H2O)6] 2H2O a
D-H
A
d(D A)
3 3 3
—(DHA)
3 3 3
3 3 3
3
N(4)-H(4) O(1w)
2.903(1)
2.922(1)
3.148(1)
3.272(1)
2.913(1)
150(2)
150(2)
167(2)
165(2)
148(2)
O(1w)-H(1w2) O(3w)#1
2.839(1)
2.963(1)
2.878(1)
2.796(1)
2.745(1)
178(2)
175(2)
174(2)
169(2)
166(2)
3 3 3
3 3 3
N(13)-H(13) O(1w)
O(2w)-H(2w1) N(1)
3 3 3
3 3 3
N(19)-H(19) O(2w)
O(2w)-H(2w2) O(3w)
3 3 3
3 3 3
N(28)-H(28) O(2w)
O(3w)-H(3w1) O(3)#2
3 3 3
3 3 3
O(1w)-H(1w1) O(2w)
O(3w)-H(3w2) O(4)#3
3 3 3
3 3 3
[H41(SO4)2(H2O)2] 10H2O b
3
N(1)-H(1) O(12)#1
3 3 3
2.704(7)
2.874(7)
2.891(6)
2.638(6)
168(6)
154
154
N(19)-H(19) O(6w)#1
3 3 3
2.854(7)
2.937(7)
2.836(6)
2.672(6)
159
156
174
171
N(4)-H(4) O(11)
N(28)-H(28) O(6w)#1
3 3 3
3 3 3
N(13)-H(13) O(11)
O(6w)-H(6w1) O(1)#2
3 3 3
3 3 3
N(16)-H(16) O(12)
3 3 3
165(6)
O(6w)-H(6w2) O(14)
3 3 3
aSymmetry transformations used to generate equivalent atoms: #1: -x þ 1, -y þ 1, -z þ 1; #2: -x, -y þ 1, -z þ 1; #3: -x, -y þ 2, -z þ 1.
bSymmetry transformations: #1: -x þ 1, -y þ 1, -z þ 1; #2: -x, -y þ 1, -z þ 1.
and the FHF- complex, [nBu4Nþ][1(FHF-)] 3H2O, crys-
tallized in the orthorhombic space group C2221. The
tetraamido macrocycles form an elongated tetragonal
“pocket” with the four diamidopyridine groups defin-
ing the four “long” sides. If the host is considered to be
roughly an elongated ellipse, it is approximately 14 A long
˚
(along the S4 axis) with a diameter of about 7 A (between
the two bridgehead amine nitrogen atoms in the same
tetraamido macrocycle) for all three structures. These
gross elliptical dimensions for the tricycle are shorter
and thicker than the pseudo-C2h structures described
later.
3
choice of space group for the N3- complex [an alternate
2
˚
nonstandard setting of P21 - C2 (No. 4)] was made to
facilitate easy comparisons between the rigorously mono-
clinic (but pseudo-orthorhombic) N3 complex and the
-
orthorhombic FHF- complex with nearly identical lattice
constants.
In each of these three structures, the host tetraamide
macrocycles are folded at the bridgehead amines and the
pyridine units are canted slightly from parallel with Npy---
Each tetraamido macrocyclic component in the three
structures is, as noted above, folded, and the diamidopyr-
idine groups form internal multiatom H-bonding net-
works involving the pyridine nitrogen, amido hydrogen,
and amine nitrogen atoms (Npy Hamide Namine).
˚
Npy and para-Cpy---Cpy distances of about 3.5 and 4.5 A,
respectively. A crystallographic C2 axis passes through
the midpoints of the C-C bonds in the two secondary
ethylene units of both [1] 6H2O and 1(FHF-). In compa-
3
3 3 3
3 3 3
rison, the N3- complex possesses only pseudo-C2 symmetry.
However, in all three structures the four diamidopyridine
groups are related by a pseudo-S4 axis perpendicular
to the crystallographic C2 (or pseudo-C2) axis, adopt-
ing alternate up/down orientations with each 90ꢀ rota-
tion (Figure 1). This conformation is achieved by twist-
ing the molecules like a towel or rope about the two
secondary ethylenediamine linkers until the two folded
These linkages provide additional rigidity and stability
as well as preorganized H-bonding “pockets,” as best seen
in Figure 1a-c. The structural similarities of the tricycle
-
in the free base, [1] 6H2O, with the linear FHF- and N3
3
complexes are the result of the placement of two carbonyl
oxygen atoms in the free base structure (one on each
macrocycle) into the “pocket” near the sites occupied by
FHF- fluorine atoms or N3- nitrogen atoms in the two

8632 Inorganic Chemistry, Vol. 49, No. 18, 2010
Kang et al.
Figure 1. Perspective views of [1] (a, d, and g), [1(N3-)] (b, e, and h), and [1(FHF-)] (c, f, and i). For clarity, water molecules and the nBu4Nþ ions were
omitted in the views of [1(N3-)] and [1(FHF-)].
˚
anion structures. The fouramide groupsusedtoform these
two additional free base H-bonds were not used for the
(Npy Hamide Namine) interactions. Rotation of these
short 2.355(5) A with nearly equal N-N distances of
1.162(6) and 1.193(6) A. The shortness of the N3- end-to-
˚
end distance is probably an artifact caused by that bond
lying perpendicular to the twin axis (see Supporting
Information for more detail), but may also be related to
the rather imperturbable strength of the azide double/
triple bond system (compared to the much weaker
H-bonded FHF-). While the FHF- ion may be slightly
bent, the N3- ion is clearly linear (168(4)ꢀ for FHF- and
179.3(4)ꢀ for N3-).
3 3 3
3 3 3
two carbonyl groups into the “pocket” therefore does not
interfere with the (normal) internal H-bonding networks
and provides additional structural stabilization/rigidity
by forming two additional internal H-bonds across the
“pocket” as best seen in Figure 1g. The carbonyl oxygen
atoms are, in fact, serving as surrogate guests. In sum-
mary, the host tricycles are virtually superimposable for
all three structures.
Pseudo C2h Structures: [1(H2O)6] 2H2O and [H41-
(SO4)2(H2O)2] 10H2O. In addition to the hexahydrate
free base described above, the tricycle also forms an
3
For the anionic complexes, the tricyclic macrocycle
3
-
holds the linear triatomic N3 ion as well as the earlier
reported FHF-9 anion via four H-bonds from the four
amido hydrogen atoms. These hydrogen atoms do not
participate in the intraligand H-bond network but are
rather directed toward the interior “cavity.” The presence
octahydrate, [1(H2O)6] 2H2O. This free base crystallizes
3
with an interesting ice-like arrangement for six of the H2O
molecules (Figure 2a,c,e), as previously communicated.18
Both the octahydrate free base and bis-SO4 complex
2-
of four H-bonds elongates the F F distance to 2.475(4)
˚
crystallize in the triclinic space group P1, with the center
of the tricycle coincident with a crystallographic inversion
center. Again the tetraamido macrocyclic units fold, and
3 3 3
-
A relative to FHF salts which range from about 2.23 to
2.34 A.17 On the other hand, the NdNdN separation is a
˚
(17) Vicente, J.; Gil-Rubio, J.; Bautista, D.; Sironi, A.; Masciocchi, N.
Inorg. Chem. 2004, 43, 5665-5675 and references therein.
(18) Kang, S. O.; Powell, D.; Day, V. W.; Bowman-James, K. Cryst.
Growth Des. 2007, 7, 606–608.

Article
Inorganic Chemistry, Vol. 49, No. 18, 2010 8633
Figure 2. Perspective views of [1(H2O)6] (a, c, and e) and [H41(SO4)2(H2O)2] (b, d, and f) complexes. Additional H2O molecules outside the cavity were
omitted for clarity.
although the structures possess crystallographicCi symmetry,
they approximate C2h symmetry with the pseudo-C2 axis
bisecting the two ethylene linkers and the pseudomirror
passing through the four pyridine nitrogen atoms
(pseudo-C2 axis perpendicular to page and pseudomir-
ror in page of Figure 2e,f ). The molecular dimensions,
[O(3w) and O(3w)0] lie outside the cavity, above and
below the ethylene linkers as seen best in Figure 2e.
Each of the four embedded H2O molecules serve as
H-bond acceptors to a pair of amide groups attached to
the same pyridine. These interactions are significantly
stronger for water molecule O(1w) than for O(2w). O(1w)
also serves as a H-bond donor to O(2w) and the Ci-related
O(3w), and O(2w) is a H-bond donor to N(1) and O(3w).
O(3w) serves as a H-bond donor to O(3w) and O(4w) in
˚
averaging about 16.4 ꢀ 6.4 A for this conformation of
the tricycle, are longer and thinner than those for the
more compact pseudo-S4 conformation. The pseudo-
C2h conformation also places the two pyridines of each
tetraamido macrocycle closer together, slightly canted
toward each other (instead of away from each other
as in the D2 structures) with Npy---Npy and para-Cpy---
symmetry-related [1(H2O)6] 2H2O moieties. The angles
between the oxygen atoms in the H-bonded (H2O)6 hexa-
gon, O(1w) O(2w) O(3w), O(2w) O(3w) O(1w)0,
3
3 3 3
3 3 3
3 3 3
3 3 3
and O(2w) O(1w) O(3w)0, are 129.52(4), 105.52(4),
3 3 3
3 3 3
Cpy separations of about 3.9 and 3.7 A, respectively
and 119.15(4)o, respectively.
˚
-
(Figure 2e,f). The internal H-bonding networks are also
different for the pseudo-C2h structures. All of the po-
tentially semicircular five-nitrogen H-bonding units,
Namine Hamide Npy Hamide Namine in the pseudo-
As opposed to the FHF- and N3 complexes, which
crystallize as the nBu4Nþ salts, the bis-SO42- complex of
1 achieves neutrality by tetraprotonation of the four
2-
bridgehead amines of the tricycle. Two SO4 ions and
two H2O molecules are associated with each host but
outside the cavity. Each of the SO4 oxygen atoms is
3 3 3
3 3 3
3 3 3
3 3 3
C2h conformation, are utilized in the water complex, if one
˚
includes a rather weak (3.16 A) interaction between one of
2-
the amine nitrogen atoms and the adjacent amide
(Figure2c). For the bis-SO42- complex this longer network
is broken down into just three H-bonds, Hamide Npy
H-bonded to one or two other atoms: O(11) to the two
amide hydrogen atoms; O(12) to two protonated amines
of a single secondary ethylenediamine linker; O(13) to
oxygen atoms of two different H2O molecules; and O(14)
3 3 3
3 3 3
Hamide, since the protonated amines break the chain.
2-
The H2O array is one of the more interesting aspects
of the octahydrate structure. The H2O network forms a
chairlike hexagonal pattern with four of the H2O mole-
cules, two for each tetraamido macrocycle, embedded
within the tricycle framework.18 Two of the H2O molecules
to a H2O oxygen atom (Table 2). Interestingly, SO4
oxygen atoms O(11) and O(14) and the H2O oxygen atom
O(6w) in the bis-SO42- structure are approximate structural
counterparts of the H2O oxygen atoms, O(2w), O(3w),
and O(1w), respectively, in [1(H2O)6] 2H2O. A chain of
3

8634 Inorganic Chemistry, Vol. 49, No. 18, 2010
Kang et al.
Figure 3. Packing diagrams for [H41(SO4)2(H2O)2] 10H2O showing: (a) the orientation of the (space filling) fused cube-hexameric arrays of H-bonded
3
2-
H2O molecules and (b) the labeled SO4 and H2O molecules without 1. Additional superscripts to atomic labels refer to the following symmetry
transformations: (’) is 1 - x, -y, -z; (“) is 1 þ x, y, z; and (*) is 2 - x, -y, -z.
Figure 4. (a) 1H NMR and (b) 19F NMR spectra of [nBu4Nþ][FHF-] and [1(FHF-)] in DMSO-d6.
water “cubes” (from the 10 “external” H2O molecules of
hydration) forms a channel between tricycles parallel to
the a axis of the unit cell by fusing with hexagonal “rings”
of H2O molecules (Figure 3).
Solution and Binding Studies. The FHF- complex was
further characterized by 1H and 19F NMR spectroscopy
1
in solution (Figure 4). In the H NMR of a 1:1 L:A
complex in DMSO-d6, the free FHF- signal at 15.4 ppm
shifts downfield (Δδ = 2.1 ppm) to 17.5 ppm. The new
signal appears as a triplet (JHF = 128 Hz) due to well-
resolved coupling of the central proton with the two
adjacent fluoride ions (Figure 4a). In the 19F NMR of
[1(FHF-)] in DMSO-d6, however, the free FHF- signal
at -145.3 ppm shifts upfield (Δδ = -6.8 ppm) to -152.1
ppm. The signal remains broad, possibly due to unre-
solved coupling with both the amide and FHF- hydrogen
atoms.9
Binding affinities of the tricyclic host 1 for anions were
Figure 5. 1H NMR titration spectra of 1 with [nBu4Nþ][FHF-] in
CDCl3. Numbers at the left side indicate the equivalent amounts of
determined by NMR titrations of the n-Bu4Nþ salts of
selected anions in DMSO-d6. Results revealed selectivity
for FHF- compared to the other simple inorganic anions
exained. FHF- affinity in CDCl3 is close to the calcula-
tion limit by NMR methods (log K ∼ 4-5). The amide
signal at 8.55 ppm was shifted downfield by 0.83 ppm
upon addition of 1.0 equiv of FHF- in CDCl3, indicative
of strong H-bonding between amide hydrogen atoms and
FHF- (Figure 5). Results indicated strong and selective
binding for FHF- (log K = 3.74), moderate binding for
FHF- added.
broadening of the amide signals, which could be the result
of both multiple stoichiometries and FHF- formation. It
is known that F- ion can facilitate the hydrogen ion
extraction from amide-,9,11,19 urea-,20 thiourea-,21 and
pyrrole-based22 anion hosts, which often results in the
-
-
H2PO4 (2.87), N3 (2.53), and CH3COO- (2.00), and
~
(19) Costere, A. M.; Banuls, M. J.; Aurell, M. J.; Ward, M. D.; Argent, S.
negligible binding for HSO4-, Cl-, Br-, I-, NO3
,
-
Tetrahedron 2004, 60, 9471–9478.
ꢀ
(20) (a) Esteban-Gomez, D.; Fabbrizzi, L.; Licchelli, M. J. Org. Chem.
-
SCN-, and ClO4 in DMSO-d6 (Figure 6). Determina-
ꢀ
2005, 70, 5717–5720. (b) Boiocchi, M.; Boca, L. D.; Gomez, D. E.; Fabbrizzi, L.;
tion of the affinity of 1 for F- was hampered due to severe
Licchelli, M.; Monzani, E. J. Am. Chem. Soc. 2004, 126, 16507–16514.

Article
Inorganic Chemistry, Vol. 49, No. 18, 2010 8635
on the chemistry of tricyclic hosts with mixed amine/amide
functionalities.
Experimental Section
All chemicals were reagent grade and were used as received
without further purification. NMR spectra were recorded on
a Bruker Avance 400 spectrometer. Chemical shifts are
reported as δ values relative to the TMS signal (δ = 0.00)
at 23 ꢀC. Mass spectra were obtained on a ZAB HS mass
spectrometer (VG Analytical Ltd., Manchester, UK) equi-
pped with an Opus data system. Fast-atom bombardment
(FAB) experiments were performed using a Xenon gun
operated at 8 keV energy and 0.8 mA emission. Samples were
added to mNBA as the matrix. Elemental analyses were
obtained from Desert Analystics, Tucson, AZ.
Bis(phthalimidylethyl)amine (3). Phthalic anhydride (10.0 g,
67.5 mmol) was added to a solution of diethylenetriamine 2
(3.20 g, 31.0 mmol) in CH3CN (200 mL). The reaction mixture
was stirred under reflux for 2 days. The solvent was evaporated
and 200 mL of EtOH was added to the residue. After stirring for
5 h, the precipitate was filtered, collected, and dried to give 3
(yield: 80%). H NMR (500 MHz, CDCl3, 25 ꢀC, TMS): δ =
7.72 (m, 4H; ArH), 7.66 (m, 4H; ArH), 3.79 (t, J (H,H) = 6 Hz,
4H; CH2), 2.99 (t, J (H,H) = 6 Hz, 4H; CH2).
Figure 6. Plots of the chemical shift of the NH proton of 1 (2 mM) upon
increasing the concentration of [nBu4Nþ][X-] in DMSO-d6.
1
formation of FHF-. The titration data of 1 with all of the
anions were consistent with 1:1 L:A- stoichiometries.
N0-Boc-2,20-bis(phthalimidylethyl)amine (4). Di-tert-butyldi-
carbonate (1.44 g, 6.60 mmol) was added to a solution of 3
(2.00 g, 5.50 mmol) with K2CO3 (2.00 g, 14.5 mmol) in CH2Cl2/
CH3CN (100 mL/100 mL). The reaction mixture was stirred for
1 day at room temperature. The solvent was evaporated and the
residue was dissolved in 200 mL of CH2Cl2. The organic phase
was washed with H2O (2 ꢀ 200 mL), dried with Na2SO4, and
concentrated. The crude product was recrystallized from a
mixture of MeOH/n-hexane to give 4 (yield: 80%) as a white
power. 1H NMR (400 MHz, DMSO-d6, 25 ꢀC, TMS): δ = 7.83
(m, 4H; ArH), 7.73 (m, 2H; ArH), 7.68 (m, 2H; ArH), 3.89 (t,
J (H,H) = 6 Hz, 2H; CH2), 3.85 (t, J (H,H) = 6 Hz, 2H; CH2),
3.57 (t, J (H,H) = 6 Hz, 2H; CH2), 3.52 (t, J (H,H) = 6 Hz, 2H;
CH2), 1.07 (s, 9H; CH3).
N0-Boc-2,20-diaminodiethylamine (5). N0-Boc-2,20-bis(phthal-
imidylethyl)amine 4 (1.00 g, 2.16 mmol) and hydrazine mono-
hydrate (2.00 mL, 41.2 mM) in EtOH (100 mL) were stirred for
1 day at room temperature. After the reaction, the precipitate
was removed by filtration, and the filtrate was evaporated and
extracted with CHCl3 (3 ꢀ 50 mL). The combined organic layers
were evaporated to give 5 as a light yellow oil (yield: 70%) which
was used for the next reaction without further purification. 1H
NMR (400 MHz, CDCl3, 25 ꢀC, TMS): δ = 3.27 (br s, 4H;
CH2), 2.84 (t, J (H,H) = 6 Hz, 4H; CH2), 1.45 (s, 9H; CH3).
Macromonocycle (6). A 3-neck round-bottom flask equipped
with two dropping funnels was filled with dry CH2Cl2 (500 mL)
under argon in a dry ice/acetone bath. The funnels were charged
with 2,6-pyridinedicarbonyldichloride (1.00 g, 4.90 mmol) in
CH2Cl2 (150 mL) in one and N0-Boc-2,20-diaminodiethylamine
5 (1.00 g, 4.90 mmol) and NEt3 (2.28 mL, 16.24 mmol) in
CH2Cl2 (150 mL) in the other. The reagents in the two dropping
funnels were added into the flask simultaneously at equal rates
over 1 h and the reaction mixture was stirred for 24 h. The
solvent was evaporated and the residue was redissolved in
300 mL of CH2Cl2. The organic phase was washed with H2O
(2 ꢀ 200 mL), dried with Na2SO4, and concentrated. The crude
product was purified by column chromatography (SiO2,
CH2Cl2/CH3COCH3, 10:3) to give pure monocycle 6 (yield:
30%). 1H NMR (400 MHz, DMSO-d6, 25 ꢀC, TMS): δ = 9.34
(m, 4H; NH), 8.11 (m, 6H; ArH), 3.52 (m, 8H; CH2), 3.37 (m,
8H; CH2), 1.41 (s, 18H; CH3). FAB MS m/z 669.3 [MH]þ.
Deprotected Macromonocycle (7). The protected macromo-
nocycle 6 (0.50 g, 0.75 mmol) was dissolved in CH2Cl2 (5 mL)
and treated with 2 mL of CF3COOH. The reaction mixture was
stirred for 5 h at room temperature, followed by evaporation of
Conclusions
The new tricyclic host provides a surprisingly rigid frame-
work for both thefree base forms andfor the binding oflinear
anions, especially for the simple triatomic FHF- and N3
-
ions. Primarily two conformations are observed, one with
pseudo-D2 symmetry, and the other with pseudo-C2h sym-
metry. These two conformations are stabilized by a “semi-
rigid” or organized structural motif consisting of semicircular
internal H-bonding networks incorporating the amide,
pyridine, and amine groups to different extents. In the
D2 symmetric host, a 3-fold H-bonding semicircle between
the pyridine, amide, and amine groups is observed. In the
pseudo-C2h case either an expanded five-atom network
- amine, amide, pyridine, amide, and amine - is observed
(in the free base) or a shortened amide, pyridine, amide in
2-
the protonated bis-SO4 complex. (Protonation of the
amines disrupts the network.) The host also offers an ideal
internal cylindrical cavity with four appropriately posi-
tioned amide H-bond donors for binding the ends of either
the N3- or FHF- ion. The semicircular H-bond preorga-
nization promotes planar H-bonding “pockets” that can
adapt to bind the triatomic guests in a 4-fold vice grip.
Thus, in summary, while the amido bicyclic cryptand
receptors we reported earlier tend to bind a single fluoride
anion very nicely by encapsulation,11 the tricyclic host with
an expanded cylindrical-like cavity between the monocyc-
lic lids shaped by the semicircular H-bonding network is
preorganized to accommodate linear triatomic anions such
as FHF- and N3-. Further studies are underway to expand
(21) (a) Gunnlaugsson, T.; Kruger, P. E.; Jensen, P.; Pfeffer, F. M.;
Hussey, G. M. Tetrahedron Lett. 2003, 44, 8909–8913. (b) Pfeffer, F. M.;
Gunnlaugsson, T.; Jensen, P.; Kruger, P. E. Org. Lett. 2005, 7, 5357–5360.
(c) Gunnlaugsson, T.; Kruger, P. E.; Jensen, P.; Tierney, J.; Ali, H. D. P.; Hussey,
G. M. J. Org. Chem. 2005, 70, 10875–10878.
(22) (a) Camiolo, S.; Gale, P. A.; Hursthouse, M. B.; Light, M. E.; Shi,
A. J. Chem. Commun. 2002, 758–759. (b) Gale, P. A.; Navakhun, K.; Camiolo,
S.; Light, M. E.; Hursthouse, M. B. J. Am. Chem. Soc. 2002, 124, 11228–11229.
(c) Camiolo, S.; Gale, P. A.; Hursthouse, M. B.; Light, M. E. Org. Biomol. Chem.
2003, 1, 741–744.

8636 Inorganic Chemistry, Vol. 49, No. 18, 2010
Kang et al.
the solvent under reduced pressure. The crude product was
purified by column chromatography (SiO2, CH2Cl2/MeOH/
NH3(aq), 20:4:1) to give deprotected macromonocycle 7 (yield:
70%). 1H NMR (400 MHz, DMSO-d6, 25 ꢀC, TMS): δ = 9.21
(br t, 4H; NH), 7.98 (m, 6H; ArH), 3.44 (br q, 8H; CH2), 2.83 (s,
8H; CH2). FAB MS m/z 469.2 [MH]þ.
For 19F NMR spectra, the aqueous NaF signal (δ = -122.4)
was used as an external standard. All 19F spectra were recorded
at 23 ꢀC and [F-] of 10 mM.
X-ray Crystallographic Studies. A detailed experimental de-
scription is provided in the Supporting Information. Complete
hemispheres of intensity data were collected for crystals of all
five compounds at 100(2) K using 0.30ꢀ-wide ω scans with
Tricycle (1). 1,2-Dibromoethane (1.00 mL, 11.6 mmol) was
added to a solution of the deprotected macromonocycle 7
(0.20 g, 0.43 mmol) with K2CO3 (0.50 g, 3.62 mmol) in CH3CN
(200 mL), and the reaction mixture was refluxed for 2 days. The
solvent was evaporated and 100 mL of H2O was added to the
residue. After stirring for 3 h, the precipitates were filtered,
collected, and dried. This crude product was purified by column
chromatography (basic Al2O3, 2% MeOH in CH2Cl2) to give a
pure macrotricycle 1 (yield: 30%). 1H NMR (400 MHz, DMSO-
d6, 23 ꢀC, TMS): δ = 8.70 (br s, 8H; NH), 7.88 (t, J (H,H) = 7.0
Hz, 4H; ArH), 7.79 (d, J (H,H) = 7.4 Hz, 8H; ArH), 3.35 (m,
16H; CH2), 2.79 (m, 24H; CH2); 13C NMR (400 MHz, CDCl3) δ
163.8 (CdO), 149.1, 138.5, and 124.6 (Ar), 54.7, 53.0, and 38.1
˚
graphite-monochromated MoKR radiation (λ = 0.71073 A)
on a Bruker SMART APEX CCD area detector mounted on
a Bruker D8 goniometer. Crystals of the hexahydrated free
ligand, [1] 6H2O, suitable for X-ray diffraction were grown by
3
slow evaporation of a CHCl3 solution. Crystals of [1(N3-)]-
[nBu4N]þ 3H2O and [1(FHF-)][nBu4N]þ 3H2O, were grown
by slow evaporation of a CH3CN solution of 1 in the presence of
3
3
excess [nBu4Nþ][N3-] and [nBu4Nþ][F-], respectively. The oc-
tahydrated H2O complex of 1, [1(H2O)6] 2H2O, was obtained
3
from a CH3CN solution of 1 in the presence of excess [nBu4Nþ]-
[Cl-]. The resulting crystalline product was not the anticipated
anion complex but was instead the neutral hydrated ligand,
(CH2). FABMSm/z989.7 [MH]þ;Anal.CalcdforC48H60N16O8
[1(H2O)6] 2H2O that contained an encapsulated ring of six
3
3
CH2Cl2 H2O: C, 53.89; H, 5.91; N, 20.52. Found: C, 53.69; H,
3
H-bonded H2O molecules.18 The bis-SO42- complex, [H41(SO4)2-
(H2O)2] 10H2O, was obtained by adding excess H2SO4 to a
solution of 1 in DMSO.
5.66; N, 20.77.
3
NMR Studies. Each titration was performed by 20 measure-
ments in DMSO-d6 at room temperature. Aliquots from a stock
solution of the nBu4Nþ salts (20 mM) were gradually added to
the initial solution of ligand (2 mM). Up to 10 anion equivalents
were added during the titrations. All proton signals were
referenced to a TMS standard. The association constants K
were calculated by EQNMR.23 All titration curves fit best in 1:1
binding modes of the ligand to anions.
Acknowledgment. The authors thank the National Science
Foundation, CHE-0316623, for support of this work and CHE-
0079282 for purchase of the X-ray diffractometer.
Supporting Information Available: Detailed crystallographic
description of the structural determination for all five com-
plexes. This material is available free of charge via the Internet at
http://pubs.acs.org.
(23) Hynes, M. J. Chem. Soc., Dalton Trans. 1993, 311–312.