The influence of the framework: An anion-binding study using fused [n]polynorbornanes

Article abstract of DOI:10.1002/asia.201301677

A series of bis-thiourea-functionalized [n]polynorbornane hosts (1-6) with increasing size were synthesized and their anion-binding properties were evaluated by using ¹HNMR spectroscopic titration and Job's plot analysis. The larger bis-thiourea-[3]polynorbornane scaffolds 4 and 5 bound acetate in a 1:1 (cooperative) arrangement, whereas the corresponding smaller norbornane host 2, identical in preorganization, bound acetate in a 1:2 (independent) arrangement. In contrast, the size of the framework had no influence on the binding of dihydrogenphosphate. These results clearly highlight the subtle influence that the framework itself can have on host-guest interactions. One anion or two? A series of bis-thiourea-functionalized [n]polynorbornane hosts (1-6) with increasing size were synthesized and their anion-binding properties were evaluated by using ¹HNMR spectroscopic titration and Job's plot analysis. Our results highlight the subtle influence that the framework itself can have on host-guest interactions.

Full text of DOI:10.1002/asia.201301677

FULL PAPER
DOI: 10.1002/asia.201301677
The Influence of the Framework: An Anion-Binding Study Using Fused
[
n]Polynorbornanes
[
a]
Benjamin M. Long and Frederick M. Pfeffer*
Abstract: A series of bis-thiourea-func-
tionalized [n]polynorbornane hosts (1–
ment, whereas the corresponding
smaller norbornane host 2, identical in
preorganization, bound acetate in a 1:2
(independent) arrangement. In con-
trast, the size of the framework had no
influence on the binding of dihydro-
genphosphate. These results clearly
highlight the subtle influence that the
framework itself can have on host–
guest interactions.
6
) with increasing size were synthesized
and their anion-binding properties
1
were evaluated by using H NMR spec-
Keywords: anions
·
host–guest
troscopic titration and Jobꢀs plot analy-
sis. The larger bis-thiourea-[3]polynor-
bornane scaffolds 4 and 5 bound ace-
tate in a 1:1 (cooperative) arrange-
systems NMR spectroscopy
·
·
remote effects
chemistry
·
supramolecular
Introduction
In host–guest chemistry, scaffold modification and function-
alization is often performed with no regard for the influence
of the molecular framework other than how it will preorgan-
[1]
ize the binding groups (e.g., fused [n]polynorbornanes and
[2]
calixarenes ). Clear exceptions include frameworks that
serve a defined second role: for example, fluorescent and
colourimetric scaffolds (e.g., anthracenes and naphthalimi-
[
2h,3]
des)
or those that directly partake in binding (e.g., calix-
[4]
[5]
pyrroles and cyclic peptides ). Outside of specific exam-
[6]
[7]
ples in which hydrophobic or solvophobic effects have
been investigated (typically using large or macrocyclic
hosts), the influence of the nonbinding, peripheral regions
of many scaffolds has not been extensively studied.
The [n]polynorbornane scaffold has been effectively used
in supramolecular chemistry
shown to preorganize urea and thiourea anion binding
groups to strongly bind target guests. We have previously
reported two similarly functionalized anion hosts: 1) a single
norbornane functionalized with endo-bis-thioureidoethyl
[8]
[1,9]
and in particular it has been
[1e]
[1a,b]
arms (1; Figure 1),
and 2) a larger [3]polynorbornane
functionalized with endo-tris-thioureidoethyl arms (6;
Figure 1). Host 6 has a “two-armed” end and a “single-
[1c,d,f]
armed” end.
The two-armed end of host 6 (highlighted
in red in Figure 1c) is structurally analogous to host 1. De-
spite these structural similarities, under comparable condi-
[
a] B. M. Long, Dr. F. M. Pfeffer
Centre for Chemistry and Biotechnology
School of Life and Environmental Sciences
Deakin University, Waurn Ponds, 3217 (Australia)
E-mail: fred.pfeffer@deakin.edu.au
Figure 1. a,c) Differences in binding stoichiometry between known hosts
and 6 when binding acetate. b) New norbornane hosts 2–5 designed to
1
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.201301677.
assess the effect of increasing framework size on anion binding. The
structural similarities between all hosts are highlighted in red.
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Benjamin M. Long and Frederick M. Pfeffer
tions the two arms of these anion hosts do not function in
an identical manner. Host 1 bound acetate in a 1:2 host–
guest (H:G) stoichiometry with each of the two “arms” of
norbornane 1 acting independently (Figure 1a). In contrast,
for the two-armed end of host 6, it was clear that the arms
worked cooperatively to bind a single acetate anion (Fig-
ure 1c). An extended [n]polynorbornane scaffold and/or an
additional anion-binding arm, present in host 6, are the only
differences between hosts 1 and 6 and are therefore most
likely to elicit the change in binding modes.
Owing to the differences highlighted above, the actual
effect that the [n]polynorbornane framework itself had on
anion binding and how it influences binding stoichiometry
was investigated, and the results are presented herein. A
series of two-armed hosts of varying size and shape have
been synthesized to determine which framework properties,
if any, influence binding mode. Hosts 2–5 have been de-
signed with increasing framework size and all lack the addi-
tional thiourea of host 2 (Figure 1). In addition to informa-
tion about how the [n]polynorbornane scaffold affects the
binding of acetate, the anion-recognition properties of these
frameworks in general was also investigated. As such, the
interaction of hosts 1–6 with a range of anions was evaluat-
Scheme 2. Synthesis of anion host 3.
conditions used previously, and diBoc 11 was formed in
56% yield.
Deprotection of 11 using 20% TFA in CH Cl followed
by subsequent reaction with 4-fluorophenylisothiocyanate
provided the new anion host 5 in 39% yield.
To synthesize host 4 (Scheme 3), quadricyclane 13 was
first treated with dimethylacetylenedicarboxylate (DMAD)
2
2
1
[11]
ed by means of H NMR spectroscopic titration, Jobꢀs plot
in a [2p–2s–2s] cycloaddition to form Smithꢀs diene 14,
analysis, and diffusion NMR spectroscopy.
which was then directly subjected to modified Weitz–Scheff-
er epoxidation conditions to form epoxide 15 (43% yield
over two steps). Norbornene epoxide 15 was then hydrogen-
Results and Discussion
Synthesis
The first step in the synthesis of new hosts 2–5 was the for-
mation of endo-diamide 7 (Scheme 1). In a one-pot reaction,
norbornene anhydride 8 was first reacted for 3 h with
a single equivalent of tert-butoxycarbonyl (Boc)-protected
Scheme 3. Synthesis of anion host 5.
ated (H , Pd/C) to form norbornane epoxide 16 quantita-
2
Scheme 1. Synthesis of anion host 2.
tively. The 1,3-dipolar cycloaddition of epoxide 16 with
alkene 7 gave Boc-protected scaffold 17 in 20% yield. De-
protection of 17 using 15% TFA in CH Cl followed by sub-
sequent reaction with 4-fluorophenylisothiocyanate provided
anion host 5 in 37% yield.
ethylene diamine (Boc-EDA) to form an acid amide, after
which time a second equivalent of Boc-EDA and 1-ethyl 3-
2
2
(
3-dimethylaminopropyl)carbodiimide (EDCI) was added.
Upon workup, diamide 7 was isolated in 58% yield. Depro-
tection of 7 using 11% trifluoroacetic acid (TFA) in CH Cl
followed by subsequent reaction with 4-fluorophenylisothio-
cyanate provided anion host 2 in low yield.
To form the final anion host 5, norbornene anhydride 8
was treated with ethylamine to give imide 19 in quantitative
yield (Scheme 4). Microwave-assisted Mitsudo reaction of
imide 19 with DMAD gave diester 20; however, a large
amount of inseparable benzene hexaester 21 was also
2
2
For host 3 (Scheme 2), norbornene anhydride 8 was suc-
[10]
II
[12]
cessfully reacted by using microwave-assisted Mitsudo
formed. Cyclotrimerization of DMAD by Ru is known,
conditions to form anhydride 10 (63% yield). Anhydride 10
was then subjected to the same one-pot diamide formation
and formation of hexaester 21 was confirmed by high-reso-
lution (HR) MS. As the next reaction in sequence was
a Weitz–Scheffer epoxidation and hexaester 21 should
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Benjamin M. Long and Frederick M. Pfeffer
fusion NMR spectroscopy were employed.
From previous studies, acetate was bound by host 1 in
a 1:2 H:G ratio, and the two-armed end of host 6 bound
only a single acetate, it is the anion most likely to highlight
the feature of the framework that facilitates cooperative
binding. To gain additional information, the interaction be-
tween 1–6 and phosphate, pyrophosphate, pimelate, and ter-
ephthalate were also evaluated (summary of results provid-
ed in Table 1).
NMR Spectroscopic Titration
+
Anions were used as their TBA (NBu4 ) salts with the ex-
ception of pyrophosphate, which was used as the TBAH
Scheme 4. Synthesis of anion host 6.
+
(
HNBu3 ) salt. The titrations were conducted in [D ]DMSO
6
using an initial host concentration of 2.5 mm. The H:G stoi-
[
14]
remain unreactive under such conditions, the Mitsudo
adduct that contained hexaester 21 (ꢀ30% mol) was used
directly in the next step.
chiometry was assessed by Jobꢀs plot (or generated from
[15]
[16]
the titration data ) and analysis of the binding isotherm.
The strength of binding was calculated by means of non-
linear least-squares regression using a fitting program or
WinEQNMR2. When 1:2 binding was identified the asso-
ciation constants are reported as K and K . Titration iso-
[13]
The mixture of 20 and 21 was subjected to Weitz–Scheffer
epoxidation conditions (Scheme 4), and whereas epoxide 22
was clearly formed (as evidenced by the disappearance of
[17]
1
2
13
the alkene C resonance (d=141.1 ppm) and new resonance
that corresponded to the cyclobutene epoxide (d=
therms, curve fitting, and Jobꢀs plots for all titrations are
available in the Supporting Information.
13
6
3.5 ppm) in the C NMR spectrum), the product was again
obtained as an inseparable mixture that contained hexaester
1. As hexaester 21 should prove to be unreactive in subse-
À
Acetate (CH CO )
3
2
2
As expected from previous studies, the binding of host
1 with acetate was confirmed as a 1:2 H:G ratio. It was
also confirmed that the two-armed end of host 6 bound
[1c]
quent cycloadditions, the mixture was again used without
further purification.
The epoxide was reacted in a 1,3-dipolar cycloaddition
[1c]
a single acetate anion.
Binding was predominantly be-
(
15 mins, 1508C) with endo-diamide 7 to form the final Boc-
protected scaffold 23, which was successfully isolated in
2% yield after column chro-
tween the thiourea groups with only a small change in
chemical shift observed for the amide protons.
6
matography (Scheme 4).
Attempted deprotection of
Table 1. Titration results: Maximum observed chemical shift for alkyl urea NÀH protons, binding stoichiome-
try, and binding constants (K
1
and/or K
2
) for hosts 1–6. Errorꢁ15% unless otherwise indicated.
23 in 20% TFA in CH Cl re-
2 2
Anion
Parameter
Host
sulted in complete decomposi-
tion of the starting material.
Thus, scaffold 23 was subjected
to milder deprotection condi-
tions (13% TFA in CH Cl ) in
the presence of PhSH as a car- phosphate
bocation scavenger. These more
dilute conditions smoothly pro-
duced the deprotected diamine,
which was subsequently treated
with 4-fluorophenylisothiocya-
nate to afford anion host 6 in
a 59% yield (Scheme 4).
[
1c]
1
2
3
4
5
6
acetate
Ddmax
2.6
1:2
3.4
2.1
1.8
1:2
3.0
2.9
1.1
1:1
2.8
–
2.6
1:2
3.9
2.1
1.7
1:2
A
–
1.3
1:1
3.1
–
2.6
A
–
–
1.9
1:2
3.4
2.6
1.3
1:1
3.4
–
2.6
1:1
2.6
–
1.6
1:2
3.4
2.6
1.2
1:1
3.1
–
2.6
1:1
2.7
–
1.7
1:2
3.2
2.6
1.4
1:1
3.3
–
2.8
1:1
2.9
–
[
a]
[b]
H:G
logK
1
2
2
logK2
Ddmax
H:G
1.9
[
b]
1:1
[
a]
logK
logK
1
3.5
–
2
pyrophosphate
pimelate
Ddmax
1.4
[
b]
H:G
1:1
logK
logK
1
3.8
–
3.5
2
Ddmax
3.6
1:1
3.2
1:1
3.0
1:1
3.1
1:1
3.0
1:1
[b]
H:G
1:1
4.8
–
[
c]
[c]
[c]
[c]
[c]
[c]
logK
logK
1
4.4
–
4.7
5.0
4.8
4.6
2
–
–
–
–
Evaluation
terephthalate
Ddmax
2.5
1:1
3.2
–
2.5
1:1
3.3
–
2.4
1:1
3.3
–
2.4
1:1
3.2
–
2.3
1:1
3.2
–
3.1
1:1
3.2
[
b]
H:G
To evaluate the strength and
stoichiometry of the interaction
of hosts 1–6 with anions,
logK
logK
1
2
–
[
a] Host self-aggregation prevented accurate determination of H:G stoichiometry or K
a
. [b] K
a
and H:G stoi-
ꢀ5
1
H NMR spectroscopic titra-
chiometry reported for the two-armed end only. [c] When calculated from NMR spectroscopic data, logK
a
[
13]
tion, Jobꢀs plot analysis, and dif- is not reliable ; an error of ꢁ20% was calculated.
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For the new hosts, the single norbornene host 2 bound
acetate in a 1:2 H:G ratio similar to the single norbornane
host 1. Unfortunately, an accurate H:G stoichiometry and
2) the 1:1 complex was stabilized by placement of the CH3
from a single acetate within a hydrophobic pocket formed
by the curvature of the [3]polynorbornane framework.
[9k,18]
K was unable to be determined for host 3 owing to host
A related example of a methyl group interacting favorably
with a cyclotribenzylene “bowl” has been reported by
a
self-aggregation. However, the titration curve and maximum
change in chemical shift (d=2.6 ppm) resembled those of
both single norbornane hosts 1 and 2.
[18b]
Schmuck et al.
Investigations into the exact cause are on-
going and will be reported in due course.
Interestingly, the new hosts that contained a [3]polynor-
bornane scaffold, hosts 4 and 5, bound acetate in a 1:1 H:G
ratio (without deprotonation; see Figure 2). Representative
À
Phosphate (H PO )
2
4
Like acetate, it was confirmed that host 1 binds phosphate
in a 1:2 H:G stoichiometry and host 6 binds a single phos-
phate anion between the two-armed end. Binding stoichiom-
etry for hosts 2–5 as determined by both analysis of the
binding isotherm and Jobꢀs plot analysis (Figure 3) was 1:2
Figure 3. Titration isotherm and Jobꢀs plot of host 4 with phosphate and
0 6
proposed H:G binding arrangement (H =2.5 mm in [D ]DMSO).
1
Figure 2. Titration isotherm and Jobꢀs plot and H NMR spectroscopic ti-
tration stack plot for the interaction of host 4 with acetate and proposed
H:G binding arrangement (H
0
=2.5 mm in [D
6
]DMSO).
in every case. For host 4 (typical of the series), a 1:2 model
was fit for calculation of K (logK of 3.4 and logK of 2.6,
a
1
2
<
15% error). K2 significantly contributed to the overall
of the [3]polynorbornane hosts, the H:G stoichiometry of
the complex formed between host 4 and acetate (Figure 2)
was determined through Jobꢀs plot analysis, inspection of
the binding isotherm, as well as an excellent fit to a 1:1
binding; as K ꢀK /4, it is likely to be a cooperative form of
2
[13]
1
1:2 binding. For host 4, Jobꢀs plot analysis also agreed that
a 1:2 complex was formed.
In contrast to the results for acetate (for which the in-
creasing size of the host did elicit a change in the H:G stoi-
chiometry), framework size had no effect on the binding of
phosphate. Indeed a more significant change to the host (ad-
dition of a third thiourea) was needed to change the binding
stoichiometry.
binding model (logK =2.6, 10% error).
a
For interactions with acetate the larger [3]polynorbornane
framework of hosts 4 and 5 does actually influence the bind-
ing stoichiometry. These hosts contain no additional H-bond
donors compared to 1 and 2 and the pre-organisation of the
ureidoethyl arms is identical to that of 1 and 2. Only the
size of the (largely hydrophobic) scaffold differs and for this
somewhat remote change to influence the binding stoichi-
ometry is remarkable. Although the exact nature of the in-
fluence exerted by the [3]polynorbornane framework is not
precisely known, two possibilities are as follows: 1) the sol-
vation shell, influenced by the larger scaffold, could allow
for more favorable binding of a single acetate than two; or
2
À
Pyrophosphate (H P O )
7
2
2
In previous studies, pyrophosphate was shown to be bound
[1c]
by host 6 in a discreet 1:1 complex (see Figure 4) in which
all six hydrogen-bond donors of the two-armed end were in-
volved (thiourea and amide). In this H:G complex, the
anion did not interact with the single-armed end of the host.
The current series of hosts (1–5) does not include the single-
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Indeed all data gathered was nearly identical including iso-
therm, logK , and the magnitude of the change in chemical
a
shift of all protons (Table 1). The binding of pyrophosphate
by hosts 1–5 provides further evidence to confirm the pro-
posed H:G arrangement of 6 with the anion in which one
pyrophosphate was bound between the arms of the two-
armed end. The binding was independent of any extra
framework and/or functionality at the single-armed end.
À
À
2
Pimelate ( O C
A
H
U
G
R
N
U
G
2
2
5
Host 6 in our previous work bound one pimelate dianion
[1c]
strongly at the two-armed end (logK =4.8; see Figure 6).
a
As such, it was again hypothesized that binding of pimelate
Figure 4. Titration isotherm of host 6 with pyrophosphate and the pro-
posed H:G binding arrangement for comparison to host 3 (Figure 5)
(
0 6
H =2.5 mm in [D ]DMSO).
armed side of host 6. Thus, it was hypothesized that binding
would be equally strong regardless of the absence of the
single-armed end.
Indeed, all hosts (1–6) clearly bound pyrophosphate in
a 1:1 complex (host 3, logK =3.4; Figure 5). The 1:1 com-
a
plexes formed were confirmed by Jobꢀs plot, binding iso-
therm analysis, and a good fit to a 1:1 model (error<15%).
Figure 6. Previously proposed H:G binding arrangement of host 6 with
[1c]
pimelate.
would be equally strong in hosts 1–5, regardless of the ab-
sence of the single-armed end.
Again this anion was bound in a similar manner by all
hosts (1–6). The binding mode (and binding strength) was
consistent amongst the entire series of hosts (see Figure 7,
for example, using host 5). Again the conservation of bind-
ing mode and strength throughout the series of hosts further
confirms that binding of pimelate occurs between the arms
of the two-armed end of host 6 and is independent of any
extra framework and/or functionality at the single-armed
end.
À
À
2
Terephthalate ( O CArCO )
2
Of the anions chosen in the current study, terephthalate was
expected to bind weakly to hosts 1–5, with the rigid tereph-
thalate (unlike pimelate) being unsuitable to fit between the
arms of the two-armed end as proposed for pimelate.
Contrary to what was expected, host 4 bound terephtha-
Figure 5. Titration isotherm and Jobꢀs plot of host 3 and pyrophosphate
late quite well (logK =3.3; Figure 8). The binding of ter-
and the proposed H:G binding arrangement (H
]DMSO).
0
=2.5 mm in
a
[
D
6
ephthalate was deemed 1:1 by Jobꢀs plot, binding isotherm
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Figure 9. Modeling (AM1) of the 1:1 and 2:2 complexes of host 4 with
terephthalate.
Figure 7. Titration isotherm and Jobꢀs plot of host 5 with pimelate and
the proposed H:G binding arrangement (H =2.5 mm in [D ]DMSO).
0
6
Diffusion of hosts 1–6 was measured by using stimulated
echo (STE) experiments in [D ]DMSO at a concentration of
6
2
.5 mm (Table 2). Host 1 and 2 were found to have a higher
diffusion rate than hosts 3, 4, 5, and 6. The similar diffusion
coefficients of hosts 3–6 and their difference from 1 and 2
indicates that the molecular feature that influences the hy-
drodynamic radius the most was the inclusion of the methyl
esters. At a lower host concentration (1.3 mm), the diffusion
of hosts 2, 3, and 4 increased. The increase in the rate of dif-
fusion indicates a small degree of host self-aggregation in
solution. This confirms the host self-aggregation noted in
the titration experiments for hosts 2 and 3 with acetate and
phosphate.
Figure 8. Titration isotherm and Jobꢀs plot of host 4 with terephthalate
=2.5 mm in [D ]DMSO).
(
H
0
6
analysis, and fit to a 1:1 model (<5% error). The same
binding (strong and 1:1 H:G) was also determined for hosts
1
, 2, 3, and 5.
Table 2. Diffusion coefficients (D) for hosts 1–6 in [D
one standard deviation (s) of the calculated diffusion coefficient.
6
]DMSO. Error is
Given that a 1:1 arrangement was considered geometrical-
À10
2 À1
Host
D [1ꢂ10 cm s ]
ly hard to construct, a 2:2 binding mode was also consid-
ered. Molecular modeling (AM1) was used to determine the
validity of both proposals (Figure 9) using host 4 and tereph-
thalate. Both 1:1 and 2:2 complexes were plausible. As both
binding arrangements were plausible, diffusion NMR spec-
troscopy was employed in an attempt to verify the binding
stoichiometry.
2
.5 mm
1.3 mm
1
2
3
4
5
6
1.46Æ0.02
1.34Æ0.05
1.21Æ0.04
1.20Æ0.01
1.21Æ0.03
1.20Æ0.01
1.43Æ0.01
1.49Æ0.02
1.35Æ0.02
1.27Æ0.04
1.22Æ0.02
9.84Æ0.03
Diffusion Studies
To gain more information about the binding mode (i.e.,
1:1 or 2:2; Figure 9) of hosts 1–6 with terephthalate, host 4
was chosen to be studied in further detail by diffusion
(Table 3). Binding of a small guest (e.g., acetate) to the
large host 4 should not drastically change the diffusion coef-
ficient. Formation of a 1:1 complex (or even a 1:2 complex)
with acetate would not significantly add to the hydrodynam-
ic radius (i.e., size) of the complex. Upon binding a large
guest in a 1:1 ratio (e.g., pimelate), a small change in diffu-
sion constant of host 4 would be expected. The same would
Diffusion NMR spectroscopy has been shown to be a power-
ful technique when applied in the field of host–guest
[19]
chemistry as a way to measure host self-aggregation and
[19,20]
association constants,
ichiometry
and as a tool to assess binding sto-
By using diffusion NMR spectroscopy,
[19,20b]
a series of experiments were undertaken to measure diffu-
sion of the anion hosts in [D ]DMSO and obtain further evi-
6
dence for the binding mode encountered with terephthalate
i.e., either 1:1 or 2:2 association).
(
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Benjamin M. Long and Frederick M. Pfeffer
Table 3. Table of diffusion coefficients (D) for host 4 in the presence of
An unexpected 1:1 binding arrangement of hosts 1–5 with
terephthalate was identified, and diffusion NMR spectrosco-
py was used to provide evidence for the somewhat strained
1:1 H:G complex by using host 4 as a model compound. The
data obtained by diffusion NMR spectroscopy also provides
a guide for the expected diffusion of fused [n]polynorbor-
1
equivalent of anion in [D
6
]DMSO at [H]=2.5 mm (error value Æ1s).
À10
2
À1
Host
Anion
D [1ꢂ10 m s ]
4
4
4
4
–
1.20Æ0.01
1.24Æ0.09
1.15Æ0.04
1.14Æ0.03
acetate
pimelate
terephthalate
nane structures in [D ]DMSO.
6
The research provided herein provides insight that the
size of framework can exert influence on the binding of
some, but not all, guests. The effect was highlighted in the
binding of acetate (in contrast to phosphate) in which the
large framework has a significant influence on binding:
a change from independent 1:2 binding to cooperative 1:1
binding between two arms.
be true of a 1:1 complex with terephthalate. However, if
host 4 was forming a 2:2 complex mode, a large change in
diffusion coefficient would be expected owing to the consid-
erable increase in hydrodynamic radius.
In the STE experiment, the diffusion coefficient for host 4
À10
2
À1
was calculated in the free state (1.20ꢂ10 m s ). The host
4
À10
2
À1
and acetate complex (1.24ꢂ10 m s ) did not have a sig-
nificantly different diffusion rate to host 4 alone. The mea-
sured diffusion constant of the host 4 and pimelate complex
Experimental Section
À10
2
À1
(
1.15ꢂ10 m s ) was smaller than what was measured for
NMR Titration
host 4. The small but statistically significant change in diffu-
sion is in line with the formation of a 1:1 complex rather
than a 2:2.
The measured value for the host 4 and terephthalate com-
plex again was smaller than what was measured for host 4
À3
A stock solution of each host was made up to 2.5ꢂ10 m in [D
6
]DMSO,
and then 600 mL of this solution was transferred to a 5 mm NMR spec-
troscopy tube and the spectrum acquired. The chemical shifts [ppm] of
the resonances that corresponded to the amide and both thiourea hydro-
gen-bond donors were recorded. An aliquot of the stock guest solution
(5.0 mL of a 3.0ꢂ10 m in [D ]DMSO solution, 0.1 equiv of guest) was
then added to the host solution in the NMR spectroscopy tube by auto-
pipette. The NMR spectroscopy tube was recapped, the solution was
À2
À10
2
À1
(
1.14ꢂ10 m s ). The slight decrease in diffusion coeffi-
6
À10
2
À1
cient (À0.6ꢂ10 m s ) equated to a small increase in hy-
drodynamic radius. The decrease in diffusion coefficient was
not sufficient to match that of a theoretical diffusion coeffi-
cient for the 2:2 complex (0.957ꢂ10 m s ). The diffu-
sion coefficient of the 4 and terephthalate complex was in
closer agreement with the diffusion coefficient of the 1:1
complex of 4 and pimelate than the theoretically calculated
1
shaken by hand, and then the H NMR spectrum was collected. Again,
the chemical shifts of the resonances that corresponded to the amide and
both thiourea hydrogen-bond donors were recorded; this process was re-
peated until 2.0 equiv of guest had been added. The aliquot was then in-
creased (10 mL, 0.2 equiv of guest), and the procedure was repeated until
a total of 4.0 equiv of guest had been added. The final additions were
made using larger aliquots (20 mL, 0.4 equiv of guest) until a total of
6.0 equiv of guest had been added. At this point, an additional 150 mL ali-
quot (3.0 equiv) was added. The data was then plotted as a titration iso-
therm.
À10
2
À1 [21]
2
:2 complex. The similarity between both diffusion coeffi-
cients provides evidence for the formation of the 1:1 com-
plex over a 2:2 complex, despite the 1:1 complex initially
being considered somewhat strained.
Diffusion NMR Spectroscopy
Stimulated echo experiments were performed using a diffusion time of
6
5
1
0 ms, a gradient time of 4 or 5 ms, and a maximum gradient value of
2 Gcm with a 500 MHz spectrometer. Each experiment consisted of
6 gradient steps with 64 or 32 scans each. Diffusion coefficients were
À1
Conclusion
calculated for hosts at both the titration concentration (2.5 mm) and
a dilute concentration (1.25 mm), and host and anion in a 1:1 ratio with
the concentration of host at both the titration concentration (2.5 mm) and
a dilute concentration (1.25 mm).
Four [n]polynorbornane hosts (2–5) were designed and syn-
thesized with 1) increasing framework size and 2) no third
thiourea (relative to host 6). The design allowed for exami-
nation of which feature of host 6 facilitated cooperation of
the two arms (the [3]polynorbornane framework itself or
the third thiourea).
For acetate, the [3]polynorbornane scaffold itself influ-
enced the ability of the thiourea groups to cooperatively
bind a single acetate anion. In contrast to phosphate, H:G
stoichiometry was only influenced by the addition of a third
thiourea moiety.
Acknowledgements
We acknowledge funding support from the Australian Research Council
(LE110100141) for diffusion NMR spectroscopic instruments.
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Received: December 18, 2013
Revised: January 7, 2014
Published online: February 13, 2014
Chem. Asian J. 2014, 9, 1091 – 1098
1098
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim