A macrocycle/molecular-clip complex that functions as a quadruply controllable molecular switch

Article abstract of DOI:10.1002/chem.200500676

Herein, we report the synthesis of a molecular clip with TTF side-walls and its binding behavior towards electron-deficient guests, namely the formation of macrocycle/molecular-clip supramolecular complexes in solution. Four different sets of external stimuli - the K⁺/[2.2.2]cryptand, NH₄⁺/Et₃N and (p-BrPh)₃NSbCl ₆Zn pairs, and heating/cooling cycles - control the movement of this molecular switch between its threaded and unthreaded states and provide color changes that are observable by the naked eye. This macrocycle/molecular-clip complex system can be considered not only as a quadruple-use molecular switch, but can also be operated by three of these stimuli as a three-input molecular NOR-functioning logic gate that may be monitored by UV-visible spectroscopy.

Full text of DOI:10.1002/chem.200500676

FULL PAPER
DOI: 10.1002/chem.200500676
A Macrocycle/Molecular-Clip Complex that Functions as a Quadruply
Controllable Molecular Switch
Pinn-Tsong Chiang,[a] Pin-Nan Cheng,[a] Chi-Feng Lin,[a] Yi-Hung Liu,[a]
Chien-Chen Lai,[b] Shie-Ming Peng,[a] and Sheng-Hsien Chiu*[a]
Abstract: Herein, we report the synthe-
sis of a molecular clip with TTF side-
walls and its binding behavior towards
electron-deficient guests, namely the
formation of macrocycle/molecular-clip
supramolecular complexes in solution.
Four different sets of external stimuli—
the K+/[2.2.2]cryptand, NH4+/Et3N and
(p-BrPh)3NSbCl6/Zn pairs, and heating/
cooling cycles—control the movement
of this molecular switch between its
threaded and unthreaded states and
provide color changes that are observa-
ble by the naked eye.This macrocycle/
molecular-clip complex system can be
considered not only as a quadruple-use
molecular switch, but can also be oper-
ated by three of these stimuli as a
three-input molecular NOR-function-
ing logic gate that may be monitored
by UV-visible spectroscopy.
Keywords: macrocycles · molecular
devices
·
molecular switch
·
pseudorotaxanes
Introduction
as well as redox-controllable switching activity.An addition-
al benefit of 3,4-disubstituted TTF moieties is the structural
unity of the molecular clip; as a consequence, some of the
complications that arise in the analysis of the binding event
may be avoided, particularly those caused by the cis–trans
photoisomerism[6] of each TTF unitꢀs central carbon–carbon
double bond, which occurs in a number of disubstituted
TTF units.[7] To the best of our knowledge, only a few exam-
ples exist of molecular clips that assemble with macrocycles
to form macrocycle/molecular-clip complexes[3] that can be
switched between their threaded and unthreaded states by
the application of external stimuli.[8] The addition and re-
moval of heat,[9] metal ions,[10] protons,[2c,11] and electrons[12]
all allow supramolecular systems to switch efficiently be-
tween different states; thus, supramolecular assemblies that
can be switched in these ways and which exhibit detectable
gains or losses in the optical signals of their different states
may be considered as multiple-input molecular logic
gates.[13] Although some elegant molecular logic gates that
have variable functions have been reported, NOR and
NAND (NOR= not or; NAND=not and) logic gates are
the most valuable because multiple copies can be wired up
to emulate all other types of logic gates.[14] In this paper, we
report a new molecular switch based on a macrocycle/mo-
lecular-clip complex whose switching behavior can be con-
trolled by 1) the addition of K+ ions (and their removal
Although many elegant pseudorotaxane-like[1] molecular
switches[2] have been developed in recent years, the number
of recognition motifs that can be exploited in the prepara-
tion of these complexes remains limited as a result of struc-
tural complexity and/or weak intermolecular interactions.
The use of clip-shaped guest molecules and their comple-
mentary macrocyclic hosts in the preparation of macrocycle/
molecular-clip complexes[3] is a valid approach to increasing
the binding affinity between host and guest molecules, be-
cause molecular tweezers[4] and clips[5] can exist in preorgan-
ized molecular structures that allow the efficient complexa-
tion of aromatic guests.We became interested in developing
a glycoluril-based molecular clip in which electron-rich tet-
rathiafulvalene (TTF) units are present as the side-walls; we
expected such a molecular clip to possess interesting molec-
ular-recognition properties towards electron-deficient guests
[a] P.-T. Chiang, P.-N. Cheng, C.-F. Lin, Y.-H. Liu, Prof. S.-M. Peng,
Prof.S-.H.Chiu
Department of Chemistry, National Taiwan University
No.1, Sec.4, Roosevelt Road, Taipei, Taiwan (ROC)
Fax : (+886)2-2498-0963
E-mail: shchiu@ntu.edu.tw
[b] Prof.C-.C.Lai
Department of Medical Genetics and Medical Research
China Medical University Hospital, Taichung, Taiwan (ROC)
+
with [2.2.2]cryptand), 2) the addition of NH4 ions (and
their removal with Et3N), 3) heating and cooling cycles, and
4) oxidation [(p-BrPh)3NSbCl6] and reduction (Zn) cycles,
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
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and which, additionally, provides color changes that are visi-
ble to the naked eye.Indeed, based on the absorptions in its
UV-visible spectra at 533 nm, this macrocycle/molecular-clip
chains.[17a,18] To confirm the enhancement in the solubility of
these oligo(ethylene glycol) chains, we synthesized molecu-
lar clip 1d by the same approach (Scheme 1).As anticipat-
ed, the molecular clip 1d has poor solubility in common or-
ganic solvents such as CH2Cl2 and CH3CN.
Although molecular clip 1a is very soluble in CH2Cl2, it is
only moderately soluble in CH3CN; the addition of N,N’-di-
methyl-4,4’-bipyridinium bis(hexafluorophosphate) (8·2PF6,
see Scheme 2) to a solution of 1a helped to dissolve any re-
maining insoluble molecular clip 1a and led to an immedi-
+
system operates—when stimulated with K+ and NH4 ions
and heat—as a three-input NOR-functioning molecular
logic gate.
Results and Discussion
Molecular clips 1a–c were synthesized from diphenylglycol-
uril derivative 2[15] in four steps (Scheme 1).The acid-cata-
lyzed condensation of 2 and the 2-thioxo-1,3-dithiole[16] gave
molecular clip 3 in 83% yield.The reaction of molecular
clip 3 and the oligo(ethylene glycol) monomethyl ether tosy-
lates 4a–c under basic conditions afforded the molecular
clips 5a–c with tri-, di-, and mono(ethylene glycol) chains,
respectively.Molecular clips 5a–c were then treated with
mercury(ii) acetate to provide the corresponding molecular
clips 6a–c.The coupling of molecular clips 6a–c with 1,3-di-
thiole-2-thione (7) gave the desired molecular clips 1a–c in
moderate yields.
We anticipated that the glycoluril-based molecular clip
1a, in which two TTF units are positioned at a suitable sepa-
ration to allow p stacking with guest species, would form
complexes with electronically complementary pyridinium
motifs between its two aromatic side-walls.[17] We incorpo-
rated four tri(ethylene glycol) chains into molecular clip 1a
not only to increase its solubility in organic solvents, but
also to partially reduce the free energy of binding during
À
the complexation process by allowing C H···O hydrogen
bonds to form between the guest pyridinium ionꢀs a protons
Figure 1.Partial 1H NMR spectra (400 MHz, CD3CN, 298 K) of a) molec-
ular clip 1a, b) an equimolar mixture of 1a and salt 8·2PF6 (10mm), and
c) salt 8·2PF6.
and the oxygen atoms of these tri(ethylene glycol) side-
Scheme 1.Syntheses of the molecular clips 1a–d.
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Molecular Devices
FULL PAPER
ate change in the color of the solution from light-yellow to
green.[19] The green color, which results from the absorption
of visible light at 653 nm, is characteristic of the charge-
transfer absorption that results from the interactions be-
tween electron-rich TTF derivatives and electron-deficient
N,N’-dialkylated bipyridinium ions.As indicated in Fig-
1
ure 1b, the H NMR spectrum of an equimolar mixture of
molecular clip 1a and the bipyridinium salt 8·2PF6 in
CD3CN (10mm) displays significant shifts in the positions of
its signals relative to those of its free components (cf.Fig-
ure 1a and c).The upfield shifts of the a and b protons of
the bipyridinium ion guest and of the CH2OAr protons of
the host suggest that p-stacking aryl–aryl interactions possi-
bly play an important role in stabilizing the (1aꢀ8)·2PF6
complex.
Scheme 3.Synthesis of molecular clip 10.
Ka (370Æ30mÀ1) for the interaction in CD3CN between mo-
lecular clip 10, whose side-walls contain only alkylated hy-
droquinone units, and the bipyridinium salt 8·2PF6; this
value is about 15-fold weaker than that for the binding be-
tween the TTF-containing molecular clip 1a and 8·2PF6.
The side-walls of both of these glycoluril-based molecular
clips (1a and 10) consist of rigid aromatic rings, which we
believe impart on these two molecules similar conformation-
al rigidities and p-stacking distances upon guest reception.
Thus, the 15-fold increase in the binding affinity of 1a to
8·2PF6 is probably the result of the increased area and
charge density of the p-electron-rich aromatic moieties of
this molecular clipꢀs side-walls.
The downfield shift of the signal arising from the MeN+
protons of the bipyridinium ion suggests the existence of
À
possible C H···O hydrogen bonding between these protons
and the tri(ethylene glycol) side-chains.A Job plot obtained
1
from H NMR spectra recorded in CD3CN affords conclu-
sive evidence of 1:1 complexation (see the Supporting Infor-
mation), that is, the formation of a 1:1 supramolecular as-
To test the formation of a macrocycle/molecular-clip com-
plex, we synthesized macrocycle 11·2PF6 in three steps
(Scheme 4).The reaction of 4-bromobenzyl bromide with
tri(ethylene glycol) under basic conditions gave the dibro-
[22]
mide 12.A subsequent Suzuki coupling reaction
with 4-
pyridineboronic acid (13) afforded the dipyridine 14, which
we then treated with a,a’-dibromo-p-xylene (15) to give the
desired macrocycle 11·2PF6 in 43% yield.
We grew single crystals of 11·2PF6 suitable for X-ray crys-
tallographic analysis by liquid diffusion of diisopropyl ether
into a solution of the macrocycle in CH3CN.The solid-state
structure (Figure 2) of 112+ reveals that the separations be-
Scheme 2.Formation of the complex ( 1aꢀ8)·2PF6.
sembly,
(1aꢀ8)·2PF6
(Scheme 2).We determined the
association constant (Ka) for
the interaction between the mo-
lecular clip 1a and the bipyridi-
nium salt 8·2PF6 in CD3CN to
be 5600Æ300mÀ1 based on the
results of a 1H NMR spectro-
scopic dilution experiment.[20]
To elucidate the importance
of the electron-rich TTF side-
arms in the recognition of
8·2PF6, we synthesized molecu-
lar clip 10 by alkylating tri-
(ethylene glycol) monomethyl
ether tosylate 4a and molecular
clip 9[21] under basic conditions
(Scheme 3).We used the 1H
NMR spectroscopic dilution
method to obtain the value of Scheme 4.Synthesis of the macrocycle 11·2PF6.
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S.-H. Chiu et al.
Figure 2.Ball-and-stick representation of the solid-state structure of mac-
rocycle 112+
.
tween the mean planes of the pairs of pyridinium and
phenyl residues are approximately 6.8 and 7.2 Š, respective-
ly.The dimensions of the pseudorectangular 112+ are ap-
proximately 13.2”7.0 Š and thus, the insertion of a p-elec-
tron-rich TTF guest unit between the two p-electron-defi-
cient pyridinium units seemed promising (cf.the accept-
ed[18b,23] aromatic p-stacking distance of 3.5 Š).
As was the case when we mixed molecular clip 1a with
the bipyridinium salt 8·2PF6, the addition of macrocycle
11·2PF6 to a suspension of 1a in CH3CN helped to dissolve
any remaining insoluble 1a; more interestingly, this process
resulted in an immediate change in the color of the solution
from light-yellow to puce.The 1H NMR spectrum of an
equimolar mixture of 1a and 11·2PF6 in CD3CN (10mm)
displays significant shifts in the positions of its signals rela-
tive to those of its free components (Figure 3).The upfield
shifts of protons Hc and Hd in macrocycle 11·2PF6 and the
protons of the TTF and CH2OAr units of molecular clip 1a
imply the existence of aryl–aryl interactions between the
two electronically complementary components.These results
suggest that the macrocycle/molecular-clip complex
(11ꢀ1a)·2PF6 is generated in solution (Scheme 5).Based on
the results of a 1H NMR dilution experiment, we deter-
mined the binding constant for the formation of this com-
plex to be 1600Æ100mÀ1.
Figure 3.Partial 1H NMR spectra (400 MHz, CD3CN, 298 K) of a) molec-
ular clip 1a, b) a mixture of 11·2PF6 and 1a (10mm each), and c) macro-
cycle 11·2PF6.
ble changes in the positions of its signals relative to the
spectra of its free components and no distinct color change
occurred, that is, the affinity of 1c for 11·2PF6 is negligible
under these conditions.In contrast, when we mixed equimo-
lar amounts of molecular clip 1b and 11·2PF6 in CDCl3/
1
CD3CN (4:1), we observed both signal movement in the H
NMR spectrum and a color change.Through 1H NMR spec-
troscopic dilution experiments we determined the associa-
tion constant for this system to be 70Æ10mÀ1.In compari-
son, the association constant for the complex formed be-
tween molecular clip 1a and 11·2PF6 under the same condi-
tions is 170Æ30mÀ1, that is, about tenfold weaker than the
affinity between these two species in pure CD3CN.This
result suggests that aryl–aryl p-stacking interactions may
play an important role in the stabilization of these com-
plexes, because p-stacking interactions are generally stron-
ger in polar solvents; the addition of a less-polar solvent, for
We used macrocycle 11·2PF6
to elucidate the importance of
the chain lengths of the oligo-
(ethylene glycol) motifs in these
molecular clips.Because molec-
ular clips 1b and 1c, which fea-
ture di(ethylene glycol) and eth-
ylene glycol side-chains, respec-
tively, are very soluble in CHCl3
but not in CD3CN, we examined
their complexation with macro-
cycle 11·2PF6 in
a
CDCl3/
CD3CN (4:1) mixture.The 1H
NMR spectrum of an equimolar
mixture of molecular clip 1c
and macrocycle 11·2PF6 in such
a solution displays only negligi- Scheme 5.Formation of the complex ( 11ꢀ1a)·2PF6.
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Molecular Devices
FULL PAPER
example, CDCl3, to a solution
of the complex in CD3CN tends
to weaken these interactions
even though it may increase the
strength of any hydrogen-bond-
ing interactions.The stronger
binding affinity of molecular
clip 1a to 11·2PF6 relative to
those of 1b and 1c towards this
macrocycle confirms the bene-
fits of incorporating sufficiently
long oligo(ethylene glycol)
chains into the constitution of
these molecular clips: not only
do they help to increase the sol-
ubility of the molecular clip but
they also enhance the degree of
guest complexation through
Scheme 6.Synthesis of the macrocycle 16·2PF6.
À
stronger C H···O hydrogen
bonding.
We grew single crystals of 5c
suitable for X-ray crystallographic analysis by slow evapora-
tion of a solution of the clip in CH3CN.The solid-state struc-
ture (Figure 4) of 5c reveals the existence of a slight struc-
73% yield.The alkylation of 17 with tri(ethylene glycol)
bis(p-toluenesulfonate) under basic conditions afforded the
dibromide 18 in 54% yield.Subsequent Suzuki coupling of
18 with 4-pyridineboronic acid (13) gave the dipyridine 19.
Macrocycle 20·2PF6 was obtained after [1+1] macrocycliza-
tion of 19 with a,a’-dibromo-p-xylene (15) followed by
anion exchange.Removal of the ketal protecting group of
macrocycle 20·2PF6 under acidic conditions and exchange of
the anions with NH4PF6/H2O afforded the desired macrocy-
cle 16·2PF6.
The structure of macrocycle 16·2PF6 is reminiscent of a
combination of a ring-expanded [18]crown-6 (18C6) unit,
which we expect to bind alkali-metal ions, and the p-elec-
tron-deficient aromatic motif of macrocycle 11·2PF6.We an-
ticipated that 1) the complementary electronic structures of
the TTF and pyridinium motifs, 2) the separation between
the two aromatic side-walls of the macrocycle suitable for p
stacking of a TTF unit, and 3) the p-stacking interactions
between the nonthreaded “exo” TTF arm of the molecular
clip and a pyridinium ring of the macrocycle would all assist
1a to complex with 16·2PF6 with reasonable affinity.
The addition of macrocycle 16·2PF6 to a suspension of 1a
in MeCN dissolved any remaining insoluble molecular clip
and led to an immediate change in the color of the solution
from light-yellow to puce, just as we had observed upon
mixing 1a and 11·2PF6.The UV-visible spectrum of the
complex formed between 11·2PF6 and 1a in MeCN (Fig-
ure 5a) displays a charge-transfer band at 533 nm that sug-
gests the formation of the macrocycle/molecular-clip com-
plex (16ꢀ1a)·2PF6.A Job plot based on this absorption in
MeCN affords conclusive evidence for 1:1 complexation
(see the Supporting Information).From the results of 1H
NMR spectroscopic dilution experiments, we determined
the association constant for the binding between macrocycle
16·2PF6 and molecular clip 1a in CD3CN to be 4900Æ
200mÀ1.
Figure 4.Ball-and-stick representations of the solid-state structure of mo-
lecular clip 5c.
tural twist in the diphenylglycoluril unit; the relative dis-
placement of the centers of the two alkoxybenzene rings is
1.2 Š. These dialkoxybenzene moieties define a tapering
cavity and the mean planes through the cavity walls are
aligned at a relative angle of 44.58.[24] The centers of the al-
koxybenzene rings are 6.5 Š apart.
Having established the feasibility of forming macrocycle/
molecular-clip complexes, we turned our attention towards
switchable versions of this system.To do so, we designed a
new macrocycle (16·2PF6, Scheme 6) in which the tri(ethy-
lene glycol) motif of macrocycle 11·2PF6 is replaced by a
ring-expanded [18]crown-6 unit.
We synthesized macrocycle 16·2PF6 from (4-bromoben-
zoyl)methanol in five steps.The carbonyl group of (4-bro-
mobenzoyl)methanol was protected by reaction with ethyl-
ene glycol under acidic conditions to give the alcohol 17 in
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S.-H. Chiu et al.
tional change in the aromatic units of macrocycle 16·2PF6,
repels the threaded molecular clip (Scheme 7).[26] However,
we cannot be certain whether this effect arises mostly
through conformational, steric, or repulsive electrostatic ef-
fects.
To remove the K+ ions complexed to macrocycle 16·2PF6,
we added an excess amount of [2.2.2]cryptand, a very strong
binder of K+ ions, to the solution.As anticipated, the puce
color of the solution returned instantly upon addition of
1
[2.2.2]cryptand. The H NMR spectrum (Figure 6c) of this
mixture appears to be similar to that of the original solution
of macrocycle 16·2PF6 and molecular clip 1a (Figure 6a);
this observation implies that the original (16ꢀ1a)·2PF6 com-
plex is regenerated in this solution.The threading/unthread-
ing process can be repeated several times by adding excess
amounts of K+ ions and [2.2.2]cryptand sequentially; more-
over, the reversible color changes allow us to monitor the
switching process directly by the naked eye.
Figure 5.The UV-visible spectra (MeCN, 15. m m, 298 K) of a) an equimo-
lar mixture of 16·2PF6 and 1a, b) the mixture obtained after adding
KPF6 (20 equiv) to solution (a), c) the mixture obtained after adding
[2.2.2]cryptand (20 equiv) to solution (b).
+
Because of the similar sizes and binding affinities of NH4
The addition of 20 equivalents of potassium hexafluoro-
phosphate (KPF6) to the puce solution of a mixture of
16·2PF6 and 1a in MeCN switched the color of the solution
back to its original yellow hue (see the Supporting Informa-
tion).The significant decrease in the intensity of the charge-
transfer band in the UV-visible spectrum (Figure 5b) and
the appearance of signals characteristic of the free molecu-
and K+ ions towards 18C6,[27] we hypothesized that this
[2]pseudorotaxane-like macrocycle/molecular-clip system
+
may be switchable through the sequential addition of NH4
ions and base.The addition of ammonium hexafluorophos-
phate (NH4PF6) to the puce solution of macrocycle 16·2PF6
and molecular clip 1a in MeCN also causes the color of the
solution to turn light yellow.The addition of an excess of
Et3N to the mixture immediately switches the color of the
solution back to puce (see the Supporting Information), that
is, addition of the base leads to the formation of NH3 and
Et3NH+ ions, neither of which binds strongly to the 18C6
motif of 16·2PF6, and, thus, molecular clip 1a once again
threads through the macrocycle to regenerate the complex
(16ꢀ1a)·2PF6.Again, the switching process can be visual-
ized by observing the color of the solution of the macrocy-
cle/molecular-clip complex; this process can be operated re-
versibly by the sequential addition of NH4PF6 and Et3N.
Because we expected the formation of the macrocycle/
molecular-clip complex (16ꢀ1a)·2PF6 to be an enthalpy-
driven process, we believed that elevating the temperature
of the solution would cause the complex to dissociate and so
the intensity of the charge-transfer absorption at 533 nm
would be reduced.To test this hypothesis, we heated an
equimolar solution of molecular clip 1a and macrocycle
16·2PF6 in CH3CN (1mm) from 298 to 353 K.The color of
the solution gradually switched from puce to light-yellow as
the temperature increased (see the Supporting Information).
Figure 7 indicates that the partial variable-temperature 1H
NMR spectrum of the mixture of 1a and 16·2PF6 at 353 K is
1
lar clip 1a (Figure 6b) in the H NMR spectrum both sug-
Figure 6.Partial 1H NMR spectra (400 MHz, CD3CN, 298 K) of a) a mix-
ture of 16·2PF6 and 1a (10mm each), b) the mixture obtained after the
addition of KPF6 (20 equiv) to the solution in (a), and c) the mixture ob-
tained after adding [2.2.2]cryptand (20 equiv) to the solution in (b).
1
a superimposition of the H NMR spectra of the two free
species; that is, the degree of complexation between 1a and
16·2PF6 is negligible at 353 K.As anticipated, when we
cooled the solution to ambient temperature, the absorptions
in both the UV-visible and 1H NMR spectra returned to
their original positions suggesting that the components of
complex (16ꢀ1a)·2PF6 are stable in solution over this tem-
perature range.Thus, complex ( 16ꢀ1a)·2PF6 can be consid-
ered to display thermal chromism[28] in solution, because the
gest the dissociation of complex (16ꢀ1a)·2PF6.This phe-
nomenon may be the result of negative allosteric behavior[25]
that arises because the 18C6-like motif of macrocycle
16·2PF6 recognizes the K+ ions and, through a conforma-
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Molecular Devices
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Scheme 7.The complexation and switching behavior of the macrocycle/molecular-clip complex ( 16ꢀ1a)·2PF6.
Figure 7.Partial 1H NMR spectra (400 MHz, CD3CN) displaying the dis-
sociation of complex (16ꢀ1a)·2PF6 at elevated temperatures: a) 353 K,
b) 333 K, c) 313 K, and d) 298 K.
Figure 8.Partial 1H NMR spectra (400 MHz, CD3CN, 298 K) of a) a mix-
ture of 16·2PF6 and 1a (2mm each), b) the mixture obtained after addi-
tion of (p-BrPh)3NSbCl6 (1 equiv) to the solution in (a), and c) the mix-
ture obtained after the addition of excess zinc powder to the solution in
(b).
reversible color changes of the macrocycle/molecular-clip
complex can be triggered thermally.
+
The rich redox chemistry of TTF units provides a very ef-
ficient tool with which to control the switching of supra-
molecular assemblies between their different states.[12f,29] We
wished to examine the possibility of using such a process to
drive our macrocycle/molecular-clip complex between its
complexed and uncomplexed states.The ( p-BrPh)3NSbCl6
species can oxidize TTF units into their corresponding
TTFC radical cations.[7c,30] The addition of one equivalent of
(p-BrPh)3NSbCl6 to a mixture of molecular clip 1a and mac-
rocycle 16·2PF6 switched the color of the solution to black
(see the Supporting Information).The appearance of signals
characteristic of the free macrocycle 16·2PF6 in the 1H
NMR spectrum (Figure 8b) suggests that dissociation of the
(16ꢀ1a)·2PF6 complex occurred presumably as a result of
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871

S.-H. Chiu et al.
electrostatic repulsion between the positively charged pyri-
dinium units of 16·2PF6 and the radical cationic TTFC+ moi-
eties of the oxidized molecular clip.The addition of zinc
+
powder to this solution reduces the TTFC motifs back to
1
their neutral form and results in a color and H NMR spec-
trum (Figure 8c) that are almost identical to those of the
original mixture of molecular clip 1a and macrocycle
16·2PF6 (Figure 8a).
These observations indicate that the complex
(16ꢀ1a)·2PF6 is stable to these switching conditions.Inter-
estingly, and in contrast to our observations during the pre-
vious three switching processes, the intensity of the UV-visi-
ble absorption at 533 nm did not decrease upon dissociation
of complex (16ꢀ1a)·2PF6.After the addition of the oxidant,
which the 1H NMR spectrum in Figure 8 proves leads to
almost complete dissociation of the complex, the UV-visible
Figure 10.a) The quadruply controllable molecular switch that can be op-
erated as b) a three-input NOR functioning molecular logic gate.
electronic circuitry when compared with the potential suita-
bility of related electronically or photonically controllable
systems.
Figure 9.Partial UV-visible spectra (MeCN, 298 K) of a) a mixture of
16·2PF6 and 1a (1mm each), b) the mixture obtained after addition (p-
BrPh)3NSbCl6 (1 equiv) to the solution in (a), and c) the mixture ob-
tained after the addition of excess zinc powder to the solution in (b).
Conclusions
absorption at 533 nm increased (Figure 9b) as a result of the
intensity of the characteristic TTFC+ absorption at 580 nm.[31]
We have demonstrated that the degree of complexation
We have prepared a new macrocycle/molecular-clip complex
that functions as a molecular switch.Four different external
stimuli—the K+/[2.2.2]cryptand, NH4+/Et3N and (p-
BrPh)3NSbCl6/Zn pairs, and heating/cooling cycles—control
the movement of this molecular switch between its threaded
and unthreaded states.The design of this supramolecular
macrocycle/molecular-clip complex has allowed us to oper-
ate a molecular switch through three fundamentally differ-
of
this
new
macrocycle/molecular-clip
complex
(16ꢀ1a)·2PF6 can be controlled reversibly through the use
of K+/[2.2.2]cryptand, NH4+/Et3N, and (p-BrPh)3NSbCl6/Zn
pairs and heating/cooling cycles.This molecular switch can
also be considered to operate as a three-input NOR-func-
tioning molecular logic gate, because the addition of any
one of three stimuli (i.e., one of K+, NH4+, or heat) to a so-
lution of 16·2PF6 and 1a results in the dissociation of the
complex (16ꢀ1a)·2PF6 and a decrease in its UV-visible ab-
sorption at 533 nm.Thus, we can consider the intensity of
the absorbance at 533 nm in the UV-visible spectrum of
complex (16ꢀ1a)·2PF6 as the output and KPF6, NH4PF6,
and heat as the inputs in the operation of a three-input
NOR logic gate (Figure 10).[32] We note, however, that the
practical difficulties involved in connecting chemically con-
trolled logic gates and the signal disruption caused by the
accumulation of side-products during the switching process
certainly limit their potential applications in complicated
ent processes: 1) the recognition of K+ and NH4 ions by
+
the 18C6-like motif of macrocycle 16·2PF6 leads to dissocia-
tion as a result of steric hindrance or conformational
changes, 2) oxidation of the TTF side-walls of molecular clip
1a leads to dissociation through electrostatic repulsion, and
3) heating the complex leads to dissociation as a result of
the enthalpic dominance of the binding event.These dissoci-
ation processes lead to color changes that are observable by
the naked eye.The addition of K +, NH4+, or heat not only
causes dissociation of the macrocycle/molecular-clip com-
plex, but also reduces the intensity of its charge-transfer ab-
sorption band at 533 nm; thus, these three inputs and one
872
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ꢁ 2006 Wiley-VCH Verlag GmbH & Co.KGaA, Weinheim
Chem. Eur. J. 2006, 12, 865 – 876

Molecular Devices
FULL PAPER
Molecular clip 5c: The procedure described above for the preparation of
5a was followed, but in this case the reaction of K2CO3 (13.8 g,
100 mmol), molecular clip 3 (5.5 g, 7.1 mmol), and tosylate 4b (6.44 g,
output characterize this macrocycle/molecular-clip complex
system as a functioning three-input molecular NOR logic
gate.
28 mmol) afforded
a light-yellow solid (2.7 g, 38%). M.p. >3118C
(decomp); 1H NMR (400 MHz, CDCl3, 298 K): d=3.46 (s, 12H), 3.69–
3.73 (m, 4H), 3.81–3.86 (m, 8H), 4.04–4.09 (m, 4H), 4.50–4.54 (m, 4H),
5.46 (d, J=16 Hz, 4H), 7.06–7.14 ppm (m, 10H); 13C NMR (100 MHz,
CDCl3, 298 K): d=38.1, 59.3, 71.6, 73.1, 85.1, 127.7, 128.6, 128.8, 130.7,
132.5, 135.0, 145.3, 156.7, 210.7 ppm; HRMS (ESI): m/z calcd.for
[M+H]+ C46H47N4O10S6): 1007.1616; found: 1007.1600.
Experimental Section
General: All glassware, stirrer bars, syringes, and needles were either
oven- or flame-dried prior to use.All reagents, unless otherwise indicat-
ed, were obtained from commercial sources.Anhydrous CH 2Cl2 and
MeCN were obtained by distillation from CaH2 under nitrogen.Anhy-
drous THF was obtained by distillation from Na/Ph2CO under nitrogen.
Reactions were conducted under nitrogen or argon.Thin-layer chroma-
tography (TLC) was performed on Merck 0.25 mm silica gel (Merck Art.
5715).Column chromatography was performed on Kieselgel 60 (Merck,
70–230 mesh).The melting points were determined by using a Fargo MP-
2D Mel-Temp apparatus and are uncorrected.In the NMR measure-
ments, deuteriated solvent was used as the lock, while either the solventꢀs
residual protons or TMS was employed as the internal standard.Chemi-
cal shifts are reported in parts per million (ppm).Multiplicities are given
as s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), and br
(broad).
Molecular clip 5d: Acetic anhydride (7.1 mL) was added to a solution of
molecular clip
3 (2.2 g, 2.9 mmol) in DMSO (22 mL) and pyridine
(7.1 mL); the mixture was then stirred for 2 h. The resulting suspension
was poured into water (150 mL), filtered, washed with water (50 mL) and
acetone (20 mL), and then dried under vacuum to afford a light-yellow
solid (2.1 g, 81%). M.p. >3258C (decomp); 1H NMR (400 MHz, CDCl3,
298 K): d=2.41 (s, 12H), 3.90 (d, J=16 Hz, 4H), 5.00 (d, J=16 Hz, 4H),
6.98–7.13 ppm (m, 10H); 13C NMR (100 MHz, CDCl3, 298 K): d=20.6,
38.0, 85.0, 127.7, 128.9, 129.3, 130.5, 132.0, 135.0, 138.2, 156.7, 167.4,
209.0 ppm; HRMS (FAB): m/z calcd for [M+H]+ (C42H31N4O10S6):
943.0364; found: 943.0386.
Molecular clip 6a: A mixture of molecular clip 5a (200 mg, 150 mmol)
and Hg(OAc)2 (250 mg, 0.8 mmol) in glacial acetic acid (1.1 mL) and
CH2Cl2 (1.5 mL) was stirred at ambient temperature for 15 min. The sus-
pension was filtered through Celite and the organic solution was washed
with saturated aqueous NaHCO3 (2”75 mL) and water (75 mL).The or-
ganic layer was dried (MgSO4) and concentrated to give molecular clip
X-ray crystallographic analysis: CCDC-274909 (5c) and CCDC-274910
(11·2PF6) contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge Crystal-
lographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
1
6a as a white solid (160 mg, 80%).Mp. .102–103 8C; H NMR (400 MHz,
Molecular clip 3: Molecular clip 2 (12.0 g, 31.7 mmol), TsOH (12.0 g,
70 mmol), and 1,2-dichloroethane (240 mL) were refluxed for 10 min in a
two-neck flask equipped with a Dean–Stark apparatus.1,3-Benzodi-
thiole-2-thione (26.4 g, 120 mmol) was added and then the mixture was
refluxed for 24 h.The mixture was poured into MeOH (450 mL), the pre-
cipitate was filtered off, suspended in DMSO (450 mL), heated to 908C
for 30 min, and then poured into MeOH (450 mL).The resulting precipi-
tate was filtered off, washed with MeOH (150 mL), and dried to give mo-
CDCl3, 298 K): d=3.36 (s, 12H), 3.53–3.55 (m, 8H), 3.64–3.85 (m, 32H),
3.89–3.94 (m, 4H), 4.01–4.06 (m, 4H), 4.43–4.48 (m, 4H), 5.44 (d, J=
16 Hz, 4H), 7.05–7.15 ppm (m, 10H); 13C NMR (100 MHz, CDCl3,
298 K): d=37.8, 58.9, 70.1, 70.5, 70.5, 70.7, 71.8, 72.9, 85.0, 127.0, 127.8,
128.6, 128.9, 130.0, 132.7, 147.0, 156.9, 189.1 ppm; HRMS (FAB): m/z
calcd for [M+H]+ (C62H79N4O20S4): 1327.4171; found: 1327.4199.
Molecular clip 6b: The procedure described above for the preparation of
6a was followed; in this case, the reaction of molecular clip 5b (180 mg,
150 mmol) and Hg(OAc)2 (250 mg, 0.8 mmol) afforded a white solid
lecular clip
3 as a light-yellow solid (20.3 g, 83%). M.p. >3058C
(decomp); 1H NMR (400 MHz, CD3SOCD3, 298 K): d=3.79 (d, J=
16 Hz, 4H), 5.36 (d, J=16 Hz, 4H), 7.04–7.22 (m, 10H), 9.66 ppm (s,
4H); 13C NMR (100 MHz, CD3SOCD3, 298 K): d=37.0, 84.5, 126.6,
127.6, 128.5, 128.6, 129.9, 133.0, 140.6, 156.6, 212.3 ppm; HRMS (FAB):
m/z calcd for [M+H]+ (C34H23N4O6S6): 774.9942; found: 774.9932.
1
(136 mg, 79%).Mp. .132–133 8C; H NMR (400 MHz, CDCl3, 298 K): d=
3.38 (s, 12H), 3.55–3.62 (m, 8H), 3.66–3.86 (m, 16H), 3.90–3.95 (m, 4H),
4.03–4.08 (m, 4H), 4.44–4.49 (m, 4H), 5.45 (d, J=16 Hz, 4H), 7.05–
7.15 ppm (m, 10H); 13C NMR (100 MHz, CDCl3, 298 K): d=38.2, 59.2,
70.4, 70.7, 72.0, 73.0, 85.1, 126.9, 127.7, 128.5, 128.7, 129.9, 132.6, 146.7,
156.7, 188.7 ppm; HRMS (FAB): m/z calcd for [M+H]+ (C54H63N4O16S4):
1151.3122; found: 1151.3170.
Molecular clip 5a: K2CO3 (13.8 g, 100 mmol) was added to a solution of
molecular clip 3 (5.0 g, 6.5 mmol) in DMF (180 mL). After stirring at
room temperature for 30 min, a solution of tosylate 4a (9.5 g, 30.0 mmol)
in DMF (20 mL) was added and the mixture was stirred for another 12 h
at 708C.The solvent was evaporated under reduced pressure and the res-
idue was partitioned between water (150 mL) and CH2Cl2 (150 mL).The
organic layer was washed with water (2”100 mL), dried (MgSO4), and
concentrated to give a crude product, which was purified by column chro-
matography (SiO2; MeOH/CH2Cl2, 2:98) to provide a yellow solid (4.0 g,
46%).Mp..129–130 8C; 1H NMR (400 MHz, CDCl3, 298 K): d=3.36 (s,
12H), 3.54–3.56 (m, 8H), 3.65–3.84 (m, 32H), 3.89–3.94 (m, 4H), 4.02–
4.07 (m, 4H), 4.44–4.49 (m, 4H), 5.44 (d, J=16 Hz, 4H) 7.05–7.13 ppm
(m, 10H); 13C NMR (100 MHz, CDCl3, 298 K): d=37.9, 59.0, 70.2, 70.6,
70.8, 71.9, 73.4, 85.1, 127.9, 128.8, 129.0, 130.9, 132.7, 135.2, 145.6, 157.0,
211.5 ppm (one carbon is missing, possibly because of signal overlap);
HRMS (FAB): m/z calcd for [M+H]+ (C62H79N4O18S6): 1359.3713;
found: 1359.3695.
Molecular clip 6c: The procedure described above for the preparation of
6a was followed; in this case, the reaction of molecular clip 5c (150 mg,
150 mmol) and Hg(OAc)2 (250 mg, 0.8 mmol) afforded a white solid
1
(118 mg, 81%).Mp. .265–266 8C; H NMR (400 MHz, CDCl3, 298 K): d=
3.46 (s, 12H), 3.68–3.72 (m, 4H), 3.82–3.86 (m, 8H), 4.03–4.08 (m, 4H),
4.49–4.54 (m, 4H), 5.47 (d, J=16 Hz, 4H), 7.08–7.13 ppm (m, 10H); 13C
NMR (100 MHz, CDCl3, 298 K): d=38.2, 59.3, 71.7, 72.7, 85.1, 126.9,
127.7, 128.5, 128.7, 129.9, 132.6, 146.7, 156.7, 188.5 ppm; HRMS (FAB):
m/z calcd for [M+H]+ (C46H47N4O12S4): 975.2073; found: 975.2086.
Molecular clip 6d: The procedure described above for the preparation of
6a was followed; in this case, the reaction of molecular clip 5d (560 mg,
0.6 mmol) and Hg(OAc)2 (950 mg, 3.1 mmol) afforded a white solid
(0.52 g, 96%). M.p. >3258C (decomp); 1H NMR (400 MHz, CDCl3,
298 K): d=2.40 (s, 12H), 3.91 (d, J=16 Hz, 4H), 4.99 (d, J=16 Hz, 4H),
6.98–7.13 ppm (m, 10H); 13C NMR (100 MHz, CDCl3, 298 K): d=20.6,
38.1, 84.9, 127.1, 127.7, 128.9, 129.2, 129.8, 132.1, 140.0, 156.8, 167.5,
187.0 ppm; HRMS (FAB): m/z calcd for [M]+ (C42H30N4O12S4): 911.0821;
found: 911.0790.
Molecular clip 5b: The procedure described above for the preparation of
5a was followed, but in this case the reaction of K2CO3 (13.8 g,
100 mmol), molecular clip 3 (5.5 g, 7.1 mmol), and tosylate 4b (8.2 g,
30 mmol) afforded a light-yellow solid (3.1 g, 37%). M.p. 173–1748C; 1H
NMR (400 MHz, CDCl3, 298 K): d=3.38 (s, 12H), 3.56–3.63 (m, 8H),
3.66–3.85 (m, 16H), 3.90–3.95 (m, 4H), 4.05–4.10 (m, 4H), 4.45–4.49 (m,
4H), 5.45 (d, J=16 Hz, 4H), 7.05–7.15 ppm (m, 10H); 13C NMR
(100 MHz, CDCl3, 298 K): d=38.1, 59.3, 70.3, 70.7, 72.0, 73.4, 85.1, 127.7,
128.5, 128.8, 130.6, 132.4, 135.0, 145.3, 156.6, 210.9 ppm; HRMS (FAB):
m/z calcd for [M+H]+ (C54H63N4O14S6): 1183.2665; found: 1183.2681.
Molecular clip 1a: Triethyl phosphite (28.6 mL) was added to a mixture
of molecular clip 6a (1.4 g, 1.1 mmol) and 1,3-dithiole-2-thione 7 (2.1 g,
15.7 mmol). The mixture was stirred at 1308C for 3.5 h, cooled to room
temperature, and filtered.The filtrate was washed with hexane (40 mL)
to afford molecular clip 1a as a light-yellow solid (500 mg, 31%).Mp..
222–2238C; 1H NMR (400 MHz, CD2Cl2, 298 K): d=3.33 (s, 12H), 3.53–
Chem. Eur. J. 2006, 12, 865 – 876
ꢁ 2006 Wiley-VCH Verlag GmbH & Co.KGaA, Weinheim
www.chemeurj.org
873

S.-H. Chiu et al.
3.55 (m, 8H), 3.63–3.81 (m, 32H), 3.89–3.94 (m, 4H), 4.03–4.08 (m, 4H),
4.39–4.43 (m, 4H), 5.38 (d, 4H), 6.35 (s, 4H), 7.10–7.17 ppm (m, 10H);
13C NMR (100 MHz, CD2Cl2, 298 K): d=38.4, 59.2, 70.9, 71.0, 71.1, 71.2,
72.4, 72.8, 85.5, 106.5, 115.4, 119.0, 128.4, 128.7, 128.8, 130.2, 131.6, 133.6,
146.5, 157.1 ppm; HRMS (FAB): m/z calcd for [M]+ (C68H82N4O18S8):
1498.3390; found: 1498.3381.
1,2-Bis{2-[4-(4-pyridyl)phenylmethoxy]ethoxy}ethane (14): 4-Pyridinebor-
onic acid (13) (0.7 g, 5.5 mmol), MeOH (18 mL), and saturated aqueous
Na2CO3 (9 mL) were added in turn to a mixture of 12 (1.1 g, 2.2 mmol),
[Pd(PPh3)4] (130 mg, 0.11 mmol), and tri-tert-butylphosphine (25mm,
4.5 mL, 110 mmol) in toluene (28 mL).The mixture was then refluxed for
24 h.After being cooled to room temperature, the mixture was parti-
tioned between aqueous NH4OH (0.1m, 80 mL) and CH2Cl2 (80 mL).
The organic phase was collected, dried (MgSO4), and concentrated to
afford a crude product, which was purified by column chromatography
(SiO2; MeOH/CH2Cl2, 2.5:97.5) to give compound 14 as a light-yellow oil
(680 mg, 64%). 1H NMR (400 MHz, CDCl3, 298 K): d=3.64–3.70 (m,
12H), 4.60 (s, 4H), 7.42–7.48 (m, 8H), 7.58 (d, J=8 Hz, 4H), 8.61 ppm
(d, J=6 Hz, 4H); 13C NMR (100 MHz, CDCl3, 298 K): d=69.7, 70.7,
70.7, 72.9, 121.4, 126.9, 128.2, 137.0, 139.4, 148.1, 149.7 ppm; HRMS
(ESI): m/z calcd for [M+Na]+ (C30H32N2O4Na): 507.2260; found:
507.2259.
Molecular clip 1b: The procedure described above for the preparation of
1a was followed; in this case, the reaction of molecular clip 6b (115 mg,
0.1 mmol), 1,3-dithiole-2-thione 7 (160 mg, 1.2 mmol), and triethyl phos-
phite (3.2 mL) afforded a light-yellow solid (42 mg, 32%). M.p. 274–
2758C; 1H NMR (400 MHz, CD2Cl2, 298 K): d=3.38 (s, 12H), 3.57–3.61
(m, 8H), 3.66–3.81 (m, 16H), 3.88–3.93 (m, 4H), 4.03–4.08 (m, 4H),
4.39–4.43 (m, 4H), 5.38 (d, J=16 Hz, 4H), 6.35 (s, 4H), 7.10–7.15 ppm
(m, 10H); 13C NMR (100 MHz, CD2Cl2, 298 K): d=38.3, 59.3, 70.8, 71.0,
72.4, 72.7, 85.5, 106.4, 115.4, 119.0, 128.3, 128.6, 128.7, 130.2, 131.6, 133.5,
146.4, 157.0 ppm; HRMS (FAB): m/z calcd for [M+H]+ (C60H67N4O14S8):
1323.2419; found: 1323.2400.
Macrocycle 11·2PF6: A mixture of 14 (700 mg, 1.4 mmol), a,a’-dibromo-
p-xylene (380 mg, 1.4 mmol), and KPF6 (270 mg, 1.4 mmol) was stirred in
DMF (200 mL) at room temperature for 7 days.The organic solvent was
evaporated under reduced pressure, the residue was dissolved in MeCN
(20 mL), and then saturated aqueous NH4PF6 (30 mL) was added.The
organic solvent was evaporated and the resulting precipitate was collect-
ed and washed with H2O (3 mL) to afford a white solid, which was puri-
fied by column chromatography (SiO2; MeOH/CH2Cl2, 3:97) to afford
Molecular clip 1c: The procedure described above for the preparation of
1a was followed; in this case, the reaction of molecular clip 6c (160 mg,
120 mmol), 1,3-dithiole-2-thione 7 (200 mg, 1.5 mmol), and triethyl phos-
phite (3.1 mL) afforded a light-yellow solid (46 mg, 24%). M.p. >3128C
(decomp); 1H NMR (400 MHz, CDCl3, 298 K): d=3.50 (s, 12H), 3.72–
3.76 (m, 8H), 3.86–3.88 (m, 4H), 4.15–4.18 (m, 4H), 4.41–4.44 (m, 4H),
5.40 (d, J=16 Hz, 4H), 6.28 (s, 4H), 7.05–7.10 ppm (m, 10H); 13C NMR
(100 MHz, CDCl3, 298 K): d=38.0, 59.3, 71.7, 72.0, 85.1, 106.2, 116.0,
118.5, 127.8, 128.4, 128.5, 129.3, 131.5, 133.1, 146.1, 156.7 ppm; HRMS
(FAB): m/z calcd for [M]+ (C52H50N4O10S8): 1146.1293; found: 1146.1344.
macrocycle 11·2PF6 as a yellow solid (550 mg, 43%).Mp..
>2728C
(decomp); 1H NMR (400 MHz, CD3CN, 298 K): d=3.53 (s, 4H), 3.55–
3.58 (m, 8H), 4.56 (s, 4H), 5.67 (s, 4H), 7.50 (d, J=8 Hz, 4H), 7.62 (s,
4H), 7.77 (d, J=8 Hz, 4H), 8.13 (d, J=7 Hz, 4H), 8.68 ppm (d, J=7 Hz,
4H); 13C NMR (100 MHz, CDCl3, 298 K): d=64.4, 70.7, 71.1, 71.4, 72.7,
125.9, 128.9, 129.5, 131.1, 133.1, 136.6, 144.5, 144.6, 157.1 ppm; HRMS
(ESI): m/z calcd for [11·PF6]+ (C38H40F6N2O4P): 733.2624; found:
733.2678.
Molecular clip 1d: The procedure described above for the preparation of
1a was followed; in this case, the reaction of molecular clip 6d (180 mg,
0.2 mmol), 1,3-dithiole-2-thione 7 (420 mg, 3.1 mmol), and triethyl phos-
phite (8.4 mL) afforded a light-yellow solid (35 mg, 16%). M.p. >3128C
1
(decomp); H NMR (400 MHz, CDCl3, 298 K): d=2.40 (s, 12H), 3.83 (d,
[2-(4-Bromophenyl)-1,3-dioxolan-2-yl]methanol (17): (4-Bromobenzoyl)-
methanol (6.45 g, 30 mmol), ethylene glycol (9.3 g, 0.15 mol), and TsOH
(200 mg, 11.6 mmol) were dissolved in benzene (300 mL) and then re-
fluxed for 3 h in glassware equipped with a Dean–Stark apparatus.The
reaction mixture was then cooled to room temperature and the organic
J=16 Hz, 4H), 4.85 (d, J=16 Hz, 4H), 5.97 (s, 4H), 6.96–7.08 ppm (m,
10H); 13C NMR (100 MHz, CDCl3, 298 K): d=20.7, 38.0, 85.0, 103.3,
118.2, 127.8, 128.7, 128.8, 129.1, 132.6, 132.7, 139.2, 156.9, 168.0 ppm (one
carbon is missing, possibly because of signal overlap); HRMS (FAB):
m/z calcd for [M]+ (C48H34N4O10S8): 1082.0041; found: 1082.0013.
solvent was evaporated.The residue was partitioned between
H 2O
Molecular clip 10: K2CO3 (1.5 g, 10.9 mmol) was added to a solution of
molecular clip 9 (0.5 g, 0.9 mmol) and tosylate 4a (1.4 g, 4.2 mmol) in
DMF (14 mL) at ambient temperature.The mixture was stirred at 90 8C
for 12 h before the solvent was evaporated under reduced pressure.The
residue was partitioned between water (500 mL) and CH2Cl2 (500 mL)
and the organic layer was washed with water (2”500 mL), dried
(MgSO4), and concentrated to give a crude product, which was then puri-
fied by column chromatography (SiO2; MeOH/CH2Cl2, 4:96) to provide
(300 mL) and CH2Cl2 (300 mL) and the organic layer was dried (MgSO4)
and concentrated.The crude product was then purified by column chro-
matography (SiO2; hexane/CH2Cl2, 4:7) to give alcohol 17 as a white
solid (5.65 g, 73%). M.p. 93–948C; 1H NMR (400 MHz, CDCl3, 298 K):
d=3.68 (s, 2H), 3.83–3.86 (m, 2H), 4.08–4.12 (m, 2H), 7.34 (d, J=6 Hz,
2H), 7.47 ppm (d, J=6 Hz, 2H); 13C NMR (100 MHz, CDCl3, 298 K):
d=65.8, 67.2, 109.2, 122.9, 128.0, 131.5, 138.7 ppm; HRMS (FAB): m/z
calcd for [M+H]+ (C10H12BrO3): 258.9970; found: 259.0000.
clip 10 as a yellow solid (580 mg, 57%).Mp..149–151
8C; 1H NMR
2,2’-(2,5,8,11-Tetraoxadodecane-1,12-diyl)bis[2-(4-bromophenyl)-1,3-diox-
olane] (18): Alcohol 17 (2.26 g, 8.8 mmol) and NaH (60%; 370 mg,
15 mmol) were added to DMF (70 mL).The mixture was stirred at room
temperature for 1 h before tri(ethylene glycol) ditosylate (1.36 g, 3 mmol)
was added slowly.The resulting mixture was stirred for 4 h and then the
reaction was quenched by the addition of MeOH (5 mL).The organic
solvent was evaporated under reduced pressure and the residue was par-
titioned between H2O (100 mL) and CH2Cl2 (100 mL).The organic layer
was collected, dried (MgSO4), and concentrated to afford a crude prod-
uct, which was purified by column chromatography (SiO2; MeCN/
CH2Cl2, 3:97) to give compound 18 as a yellow oil (1.02 g, 54%). 1H
NMR (400 MHz, CDCl3, 298 K): d=3.49 (s, 4H), 3.53–3.55 (m, 4H),
3.63–3.67 (m, 8H), 3.79–3.83 (m, 4H), 4.06–4.09 (m, 4H), 7.35 (d, J=
6 Hz, 4H), 7.43 ppm (d, J=6 Hz, 4H); 13C NMR (100 MHz, CDCl3,
298 K): d=65.2, 70.5, 70.5, 71.6, 75.2, 108.4, 122.0, 127.6, 130.7,
138.8 ppm; HRMS (FAB): m/z calcd for [M+H]+ (C26H33Br2O8):
631.0542; found: 631.0500.
(400 MHz, CDCl3, 298 K): d=3.36 (s, 12H), 3.50–4.20 (m, 52H), 5.49 (d,
J=16 Hz, 4H), 6.71 (s, 4H), 7.00–7.06 ppm (m, 10H); 13C (100 MHz,
CDCl3, 298 K): d=37.4, 59.1, 70.2, 70.3, 70.5, 70.7, 70.8, 71.9, 85.1, 114.4,
127.8, 127.9, 128.0, 133.7, 150.4, 157.2 ppm (the signal of one carbon atom
is missing, possibly because of signal overlap); HRMS (FAB): m/z calcd
for [M]+ (C60H82N4O18): 1147.5702; found: 1147.5704.
1,2-Bis[2-(4-bromophenylmethoxy)ethoxy]ethane (12): NaH (60%; 1.0 g,
24 mmol) was added in small portions to a solution of tri(ethylene glycol)
(1.2 g, 8.0 mmol) in DMF (80 mL) and then the resulting mixture was
stirred at room temperature for 1 h.4-Bromobenzyl bromide (60.g,
24 mmol) was added and then the mixture was stirred at ambient temper-
ature for 18 h.MeOH (5 mL) was added to quench the reaction and then
the organic solvent was evaporated under reduced pressure.The residue
was partitioned between H2O (50 mL) and CH2Cl2 (50 mL) and the or-
ganic layer was dried (MgSO4) and concentrated to give a crude product,
which was purified by column chromatography (SiO2; EtOAc/hexane,
3:7) to give compound 12 as a yellow oil (3.49 g, 90%). 1H NMR
(400 MHz, CDCl3, 298 K): d=3.59–3.61 (m, 4H), 3.65–3.67 (m, 8H), 4.83
(s, 4H), 7.19 (d, J=8 Hz, 4H), 7.43 ppm (d, J=8 Hz, 4H); 13C NMR
(100 MHz, CDCl3, 298 K): d=69.6, 70.6, 70.6, 72.4, 121.3, 129.1, 131.3,
137.1 ppm; HRMS (ESI): m/z calcd for [M+H]+ (C20H25Br2O4):
487.0120; found: 487.0119.
4,4’-[2,5,8,11-Tetraoxadodecane-1,12-diylbis(1,3-dioxolane-2,2-diyl-4,1-
phenylene)]dipyridine (19): 4-Pyridineboronic acid 13 (0.22 g, 1.8 mmol),
MeOH (6 mL), and saturated aqueous Na2CO3 (3 mL) were added in
turn to a mixture of 18 (0.4 g, 630 mmol), [Pd(PPh3)4] (42 mg, 40 mmol),
and tri-tert-butylphosphine (25mm, 1.44 mL, 40 mmol) in toluene (9 mL).
874
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Chem. Eur. J. 2006, 12, 865 – 876

Molecular Devices
FULL PAPER
This mixture was then refluxed for 24 h.After cooling to room tempera-
ture, the mixture was partitioned between aqueous NH4OH (0.1m,
20 mL) and CH2Cl2 (20 mL). The organic phase was collected, dried
(MgSO4), and concentrated to afford a crude product, which was purified
by column chromatography (SiO2; MeOH/CH2Cl2, 4:96) to give com-
pound 19 as a light-yellow oil (290 mg, 73%). 1H NMR (400 MHz,
CDCl3, 298 K): d=3.51 (s, 4H), 3.54–3.66 (m, 4H), 3.67–3.69 (m, 4H),
3.70 (s, 4H), 3.84–3.87 (m, 4H), 4.10–4.13 (m, 4H), 7.49 (d, J=6 Hz,
4H), 7.60 (s, 8H), 8.63 ppm (br, 4H); 13C NMR (100 MHz, CDCl3,
298 K): d=65.2, 71.5, 75.2, 108.6, 121.4, 126.5, 126.8, 137.7, 141.1, 147.8,
149.8 ppm (the signals of two carbon atoms are missing, possibly because
of signal overlap); HRMS (FAB): m/z calcd for [M+H]+ (C36H41N2O8):
629.2863; found: 629.2900.
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xylene (0.4 g, 1.6 mmol), and KPF6 (0.33 g, 1.6 mmol) in DMF (230 mL)
was stirred at room temperature for 7 days.The solvent was evaporated
under reduced pressure, the residue was dissolved in MeCN (20 mL), and
then saturated aqueous NH4PF6 (30 mL) was added.The organic solvent
was evaporated and the resulting precipitate was collected and washed
with H2O (3 mL) to afford a white solid, which was purified by column
chromatography (SiO2; MeOH/CH2Cl2, 5:95) to afford macrocycle
20·2PF6 as a yellow solid (1.40 g, 86%). M.p. 179–1828C; 1H NMR
(400 MHz, CD3CN, 298 K): d=3.33–3.36 (m, 8H), 3.47–3.49 (m, 4H),
3.66 (s, 4H), 3.83–3.85 (m, 4H), 4.03–4.05 (m, 4H), 5.70 (s, 4H), 7.60 (s,
4H), 7.66 (d, J=9 Hz, 4H), 7.82 (d, J=9 Hz, 4H), 8.19 (d, J=7 Hz, 4H),
8.69 ppm (d, J=7 Hz, 4H); 13C NMR (100 MHz, CD3CN, 298 K): d=
64.2, 65.9, 68.2, 70.6, 70.7, 71.8, 75.6, 108.8, 126.1, 128.5, 131.1, 133.9,
136.1, 145.0, 146.0, 157.0 ppm; HRMS (FAB): m/z calcd for [20·PF6]+
(C44H48O8N2F6P): 877.3052; found: 877.3062.
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(2 mL) and then refluxed for 3 days.The organic solvent was evaporated
under reduced pressure, the residue was dissolved in MeCN (20 mL), and
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column chromatography (SiO2; MeOH/CH2Cl2, 5:95) to afford the mac-
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>2458C
(decomp); 1H NMR (400 MHz, CD3CN, 298 K): d=3.46 (s, 4H), 3.51–
3.54 (m, 4H), 3.63–3.65 (m, 4H), 4.67 (s, 4H), 5.71 (s, 4H), 7.62 (s, 4H),
7.89 (d, J=8 Hz, 4H), 8.08 (d, J=8 Hz, 4H), 8.19 (d, J=8 Hz, 4H),
8.74 ppm (d, J=8 Hz, 4H); 13C NMR (100 MHz, CD3CN, 298 K): d=
65.1, 71.3, 71.6, 71.9, 76.2, 127.3, 129.8, 130.9, 131.8, 136.9, 138.9, 139.1,
145.6, 156.9, 198.2 ppm; HRMS (FAB): m/z calcd for [16·PF6]+
(C40H40O6N2F6P): 789.2528; found: 789.2540.
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Received: June 13, 2005
Published online: October 5, 2005
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