Imine macrocycle with a deep cavity: Guest-selected formation of syn/anti configuration and guest-controlled reconfiguration

Article abstract of DOI:10.1002/chem.201405912

A dynamic covalent bond is one of the ideal linkages for the construction of large and robust organic architectures. In the present article, we show how organic templates can efficiently transform a complex dynamic imine library into a dynamic imine macrocycle. Not only is the constitution well controlled, but also the syn/anti host configuration is efficiently selected and even the orientation of the guest in the asymmetric cavity of the host can be well aligned. This is attributed to the delicate balance and the cooperation of multiple noncovalent interactions between the hosts and the guests. Through sequential additions of three guests in appropriate amounts, controlled structural reconfiguration of dynamic covalent architectures has been achieved for the first time.

Full text of DOI:10.1002/chem.201405912

DOI: 10.1002/chem.201405912
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Host–Guest Chemistry |Hot Paper|
Imine Macrocycle with a Deep Cavity: Guest-Selected Formation
of syn/anti Configuration and Guest-Controlled Reconfiguration
Zhenfeng He, Gang Ye, and Wei Jiang*[a]
Abstract: A dynamic covalent bond is one of the ideal
linkages for the construction of large and robust organic
architectures. In the present article, we show how organic
templates can efficiently transform a complex dynamic
imine library into a dynamic imine macrocycle. Not only is
the constitution well controlled, but also the syn/anti host
configuration is efficiently selected and even the orientation
of the guest in the asymmetric cavity of the host can be
well aligned. This is attributed to the delicate balance and
the cooperation of multiple noncovalent interactions be-
tween the hosts and the guests. Through sequential addi-
tions of three guests in appropriate amounts, controlled
structural reconfiguration of dynamic covalent architectures
has been achieved for the first time.
Introduction
ical functions are realized not only through the structural re-
constitution of biological assemblies but also through more
subtle structural reconfiguration,[19,20] for example, protein fold-
ing.[21] It was pointed out by Lehn more than a decade ago
that dynamic assembly may also undergo a configurational
change without a change in constitution.[22] However, switch-
ing between different configurational structures has only been
realized through reconstitution by exchanging building blocks
with different configurations.[23] To the best of our knowledge,
dynamic covalent assembly capable of controlled reconfigura-
tion has never been reported.[24] This is presumably due to the
apparent difficulties in efficiently and simultaneously con-
trolling configuration and constitution of a complex system.
Nevertheless, controlled reconfiguration may provide
complex functions through more subtle structural adaptability
and morphological changes of the assemblies.
Chemical self-assembly[1] has attracted extensive attention in
the last two decades for its applications in the construction of
nanoarchitectures and molecular machines and switches.[2]
However, the question remains: “how far can we push chemi-
cal self-assembly?”[3] The dynamic covalent bond,[4] which
shares the chemical stability of kinetically inert covalent bond
and the reversibility of noncovalent interaction, is one of the
ideal linkages for further pushing the limit of chemical self-as-
sembly. During the last decade, many intricate molecular archi-
tectures based on the dynamic covalent bond have been con-
structed, such as Borromean rings,[5] Solomon links,[6] pentafoil
knots,[7] porous organic molecules,[8] covalent organic frame-
works,[9] molecular capsules and cages,[10] macrocycles,[11] and
other multicomponent assemblies.[12] In most of these architec-
tures, very rigid building blocks are involved. Building blocks
with even limited flexibility usually lead to a dynamic covalent
library,[13] in which a complex mixture exists.[14] To convert a
dynamic covalent library into a dynamic covalent assembly,
external templates[15] are frequently used as delicate “levers”
through multiple noncovalent interactions. Because of strong
coordination bonds, metal ions are popular templates. In con-
trast, organic templates with weaker noncovalent interactions
usually show limited amplifications over certain library mem-
bers,[16] and their efficiency and selectivity are rarely exciting.[17]
It has been reported that several dynamic assemblies can
undergo structural reconstitution by exchanging building
blocks among different constituents.[18] In nature, many biolog-
Herein, we introduce two building blocks
1 and 2
(Scheme 1), which carry two aldehyde and two amine groups,
respectively. These two molecules share the same structural
backbone: the bis-naphthalene cleft. The low symmetry of this
skeleton results in syn/anti configurational isomerism in the
[1+1] imine macrocycle 3. In the absence of a template, the
equimolar mixture of dialdehyde 1 and diamine 2 constitutes
a complex dynamic covalent library with many constitutions
and configurations. Surprisingly, only one equivalent of an ap-
propriate organic template can transform this complex mixture
into a single configurational isomer. The detailed studies reveal
that the two isomers have different steric and structural
requirements for the templates, and the high templating
efficiency and selectivity result from the cooperation among
multiple noncovalent interactions. Finally, by tuning the addi-
tion sequence and amounts of three templates, controlled
reconfiguration between these two host isomers has been
realized.
[a] Dr. Z. He, G. Ye, Dr. W. Jiang
Department of Chemistry
South University of Science and Technology of China
Xueyuan Blvd 1088, Shenzhen, 518055 (P.R. China)
E-mail: jiangw@sustc.edu.cn
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201405912.
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many constitutions and configu-
rations may exist in this solution.
1
Indeed, the H NMR spectrum
(Figure 1a) of the equimolar mix-
ture of 1 and 2 is very compli-
cated. Broadened signals sug-
gest that many constitutional
and configurational structures
coexist. Notably, the signals of
free 1 and 2 almost completely
disappeared, indicating that
macrocyclic structures are pre-
dominant in this solution. This is
indirectly supported by many
triplet
signals
at
d=1.2–
ꢀ0.3 ppm (the Supporting Infor-
mation, Figure S1), which are at-
tributed to the methyl groups of
1 and 2. These methyl groups
may sit inside the cavities of
many different macrocycles and
experience different shielding ef-
fects.
Scheme 1. Chemical structures of dialdehyde 1, diamine 2, imine macrocycles 3 in syn (3-syn) and anti (3-anti)
configurations, and guests 4a–4g and 5a–5g. Numberings on the structures are used for the assignments of
NMR signals. Protons b and c in 3 are distinguished by that proton c is the one close to proton 2’ in space, and
the other one is proton b.
Results and Discussion
Templated formation of [1+1] macrocycle
We chose the imine bond[25] as the dynamic covalent bond, be-
cause it is easy to form and aldehyde and amine groups are
easy to install. The bis-naphthalene cleft was selected as the
skeleton for three reasons: a) Its curvature facilitates the forma-
tion of macrocycles and the macrocycle usually encourages
noncovalent interactions due to the macrocyclic effect; b) The
rigid cleft structure prevents the formation of the often-seen
planar imine macrocycle,[11] thus a deep cavity can be main-
tained to maximize host–guest contacts and thus the tem-
plating efficiency; c) More importantly, low symmetry of the
1
cleft introduces syn/anti configurational isomerism in [n+n]
macrocycles, with which we can demonstrate configurational
selectivity and structural reconfiguration.
Figure 1. Partial H NMR spectra (400 MHz, CDCl3/CD3CN=1:1,
[1]=[2]=4.0 mm, 300 K) of the equimolar mixture of 1 and 2 in (a) the
absence or the presence of one equivalent 4d2+ (b), or 5d2+ (c). The
assignments of all the peaks are based on H, 1H-COSY and H, 1H-ROESY
1
1
Dialdehyde 1 and diamine 2 have been synthesized by mod-
ifying the literature procedures.[26] The [1+1] macrocycle 3 has
two isomers: 3-syn and 3-anti (Scheme 1). These two structures
are reminiscent of the cone and 1,2-alternate conformations
of calix[4]arene, respectively.[27] They share the same bond
linkages, but cannot interconvert through bond rotation. To
convert between 3-syn and 3-anti, both imine bonds have to
be broken and reconnected. Consequently, they are configura-
tional isomers. As discussed above, this configurational isomer-
ism also exists for larger [n+n] macrocycles. In the equimolar
mixture of 1 and 2, the smallest [1+1] macrocycle 3 is pre-
ferred entropically; however, high rigidity of the bis-naphtha-
lene cleft and low symmetry of imine bond may cause too
much strain in 3, thus favoring larger macrocycles. Taking all
these into consideration, a very complicated mixture with
NMR experiments.
The addition of only one equivalent of organic cation 4d2+
or 5d2+ transformed this complicated NMR spectrum into
a very clean NMR spectrum with sharp and well-defined peaks
(Figure 1b and c, and the Supporting Information, Fig-
ure S1).[28] Both free 1 and 2 disappeared completely and the
aldehyde signal was not detected at all, ruling out any open-
chained structures. Careful analysis indicates either of the dia-
ldehyde and the diamine exists in only one chemical environ-
ment, suggesting that only one host isomer exists in each of
these two solutions. This is highly suggestive of [1+1] macro-
cycle, but a larger macrocycle with high symmetry cannot be
excluded. ESI mass spectrometric experiments (the Supporting
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Information, Figures S2 and S3) confirmed that it is the [1+1]
macrocycle 3 that is responsible for both clean NMR spectra:
For the guest 4d2+, the most intense peak at m/z 654 can be
assigned to [4d@3]2+; For the guest 5d2+, the peaks at m/z
634 and 1413 are attributed to [5d@3]2+ and [5d-PF6@3]+,
respectively. In addition, these two NMR spectra are distinctly
different, suggesting that they may originate from different
host isomers.
alkyl protons of the host. Although in the case of isomer II, the
two DABCOs have NOE contacts with both the aromatic and
alkyl protons of the host. For both isomers, the two DABCOs
of guest 4d2+ locate at different chemical environments, and
should have different chemical shifts. Consequently, the differ-
ent NOE effects between the hosts and the guests are distin-
guishable. Indeed, it is observed (the Supporting Information,
Figure S7) that one DABCO has NOE contacts with only aro-
matic protons 1 and 1’, whereas the other one is only close to
the alkyl groups, confirming isomer I is the predominant
structure in the equimolar mixture of 1, 2, and 4d2+
.
Structural assignments of syn and anti isomers
As discussed above, the NMR spectrum of 5d2+@3 is dis-
tinctly different from 4d2+@3 in which 3 is already assigned to
3-syn. Consequently, 3-anti may be involved in 5d2+@3. We
again performed molecular computation on all the possible
structures of 5d2+@3. Although 5d2+ is a symmetric guest,
1H NMR spectrum (the Supporting Information, Figure S1) indi-
cates that only one alkyl group is encapsulated in the cavity of
3. Therefore, the effective binding site of 5d2+ is asymmetric.
The two configurations of the macrocycle 3 are both asymmet-
ric. Consequently, there are four possible combinations be-
tween two host configurations and two guest orientations. In
all these four energy minimized structures (Figure 3a), indeed
only one alkyl group is encapsulated inside the cavity of the
host.
Numerous attempts to obtain single crystal structures of 5d2+
@3 and 4d2+@3 have been unsuccessful so far. Fortunately,
their structures can be even more thoroughly studied through
molecular computation. Compound 4d2+ is a symmetric guest,
but there are two isomers for 3. Therefore, two assembly iso-
mers are possible. Their energy minimized structures are
shown in Figure 2a. The detectable difference between these
two host structures is the spatial proximity among protons a,
b, c, and 2’ as shown in Figure 2a: For isomer I, proton
a should have nuclear Overhauser effect (NOE) contact with
proton b, whereas for isomer II, proton a is in close proximity
to proton c. By using a ROESY NMR experiment, it should be
easy to distinguish these two isomers and assign the absolute
configuration of 3 in the presence of 4d2+
.
Again, the NOE contacts among protons a, b, c, 2, and 2’ are
distinctly different for all the four structures. The ROESY NMR
spectrum (Figure 3b) of 5d2+@3 supports isomer I: 1) The
NOE effect between proton a and 2 is not observed (the Sup-
porting Information, Figure S9), consequently, isomers II and III
can be ruled out; 2) proton a has NOE correlation with proton
c and 2’, but not with proton b, excluding the isomer IV. Thus,
Figure 2. a) Energy minimized structures of two possible isomers of 4d2+@3
at the AM1 level of theory. The protons a, b, c, and 2’ are rendered to show
1
possible NOE contacts; b) partial H, 1H-ROESY NMR spectrum (500 MHz,
CDCl3/CD3CN=1:1, 4.0 mm, 300 K) of 4d2+@3.
The ROESY NMR spectrum of 4d2+@3 (Figure 2b) indicates
that proton a only has NOE contact with proton b but not
with proton c, thus supporting isomer I and that 3 is in its syn
configuration. This assignment is further supported by the
NOE correlations between the host and the guest (the
Supporting Information, Figure S7): For isomer I, one 1,4-diazo-
bicyclo[2.2.2]octane (DABCO) should have NOE contact with
the aromatic protons of the host, and the other is close to the
Figure 3. a) Energy minimized structures of four possible isomers of 5d2+@3
at the AM1 level of theory. The protons a, b, c, 2, and 2’ are rendered to
show possible NOE contacts. b) Partial H, H-ROESY NMR spectrum
(500 MHz, CDCl3/CD3CN=1:1, 4.0 mm, 300 K) of 5d2+@3.
1
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isomer I is the only structure that can explain the observed
NOE correlations, and thus 3 is in the anti-configuration.
The assignments of the configurations of 3 in the assemblies
4d2+@3 and 5d2+@3 are also supported by 1D NMR spectra.
For 3-syn, the alkyl groups of 1 and 2 experience similar chemi-
cal environments and should have similar chemical shifts. Al-
though in 3-anti, the two alkyl groups locate at the two sides
of the asymmetric aromatic backbone and experience different
chemical environments and thus may show different chemical
shifts. This is actually observed: The signals of two butyl
1
groups are almost indistinguishable in the H NMR spectrum of
4d2+@3 (e.g., see protons 11 and 11’ in the Supporting Infor-
mation, Figure S1f), whereas they show clearly different chemi-
1
cal shifts in the H NMR spectrum of 5d2+@3 (e.g., see protons
11 and 11’ in the Supporting Information, Figure S1b). This fur-
ther consolidates our assignments of 4d2+@3-syn and 5d2+
@3-anti. In addition, in the models of 4d2+@3-syn and 5d2+
@3-anti, only one alkyl group of the guests sits inside the host
cavity. This is also in line with the large upfield shift of alkyl
groups of guests.[29] Therefore, the structures of 4d2+@3-syn
and 5d2+@3-anti can be unambiguously assigned. Based on
the COSY and ROESY spectra (the Supporting Information,
Figures S4–S9), we can assign all the peaks in Figure 1b and c.
Besides the difference on the host alkyl protons, the more
diagnostic differences between these two host isomers are the
chemical shifts and patterns of protons b and c next to the
imine groups.[30]
Figure 4. a) Cavity sizes, and b) lengths of 3-syn and 3-anti, and c) structural
parameters of guests 4d2+ and 5d2+. These structures are the energy mini-
mized structures at the AM1 level of theory. The butyl groups in the hosts
were shortened to methyl groups for viewing clarity.
length in 4d2+ will significantly affect the template effect and
thus the distribution of 3-syn and 3-anti: An alkyl linker that is
too short will cause steric clashes between DABCO and the
host, disfavoring the formation of [1+1] macrocycle; however,
one that is too long will release the steric hindrance between
DABCO and the long cavity of 3-anti, thus encouraging the for-
mation of 3-anti. However, the change on the alkyl group of
5d2+ may not obviously influence the predominance of 3-anti.
To test this hypothesis, guest series 42+ and 52+ (Scheme 1)
with the alkyl length from two to eight methylene groups
It is striking that only one equivalent of template can
transform a complex dynamic covalent library into a dynamic
covalent assembly with well-controlled configuration in such
a dramatic and clean way. In particular, the predominant exis-
tence of 5d2+@3-anti is remarkable: Not only the host consti-
tution and configuration is well controlled through the guest
templation, but also the orientation of the guest inside the
asymmetric cavity of the host is perfectly aligned. High preci-
sion on tuning both the host structure and the “secondary
structure” of the final complex is achieved.
1
have been synthesized. H NMR experiments of the equimolar
mixture of 1, 2, and the individual guest have been performed
(the Supporting Information, Figures S10 and S17), and the
ratios between 3-syn and 3-anti in the presence of different
guests are listed in Table 1. Guests 4a2+ and 4b2+ with alkyl
lengths that are too short do not fit to any host cavity, show-
ing no obvious formation of 3. Four methylene groups in 4c2+
seems to be long enough to avoid the destructive steric repul-
sion between DABCO and the thin cavity of 3-syn. However,
broadened signals are already observed, suggesting the exis-
tence of unspecific structures. For the guests with longer than
five methylene groups, compound 3-anti was observed to-
gether with 3-syn, as confirmed by ROESY NMR and MS experi-
ments (the Supporting Information, Figures S11–S16). Their
ratio changes drastically by increasing the alkyl lengths of the
guests. For the guest 4g2+ with eight methylene groups, the
syn and anti isomers exist in an almost equal amount. This
supports our hypothesis that longer alkyl group releases the
potential steric repulsion between DABCO and 3-anti, encour-
aging the formation of 3-anti. In addition, for the guests 4e2+
–4g2+, there are also broadened peaks, indicating the exis-
tence of unspecified structures. Clearly, guest 4d2+ with five
methylene units, which can perfectly control the balance be-
tween the formation of [1+1] macrocycle and the selection of
the configuration, is the perfect fit to the cavity of 3-syn.
Origin of selectivity over syn/anti configuration
What determines the high selectivity of templates 4d2+ and
5d2+ in the formations of 3-syn and 3-anti, respectively? The
cavity sizes of 3-syn and 3-anti are similar (Figure 4a), but their
cavity lengths are remarkably different (Figure 4b): the cavity
of 3-syn is about 10 ꢁ long, whereas the length of the cavity of
3-anti is about 13 ꢁ. In addition, the cavity of 3-syn is narrow,
precluding the encapsulation of the bulky DABCO. In contrast,
the cavity of 3-anti is more open, and can shallowly swallow at
least one DABCO group.
The length between two quaternary nitrogen atoms in 4d2+
is 10 ꢁ (Figure 4c), which fits perfectly the cavity of 3-syn,
whereas the length of the effective binding site of 5d2+ also
matches that of the cavity of 3-anti. Guest 4d2+ has only one
more DABCO than the effective binding site of 5d2+. Thus, it
may be the second DABCO on 4d2+ that prevents the forma-
tion of 3-anti due to steric hindrance, leading to the quantita-
tive formation of 3-syn. If that is true, changing the alkyl
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Table 1. The ratio between 3-syn and 3-anti in the presence of individual
guest 4a2+–4g2+ or 5a2+–5g2+ as detected by NMR experiments.
4a2+ 4b2+
4c2+
4d2+
4e2+
4 f2+
4g2+
[a]
[a]
syn/anti
syn/anti
–
–
93:7[b] >99:1[c] 81:19 74:26 54:46[b]
5a2+ 5b2+
5c2+
5d2+
5e2+
5 f2+
5g2+
[a]
–
15:85[b] 8:92
5:95
11:89 15:85 16:84
[a] No templated formation of 3 was observed. [b] Unspecific structures
exist as indicated by the broadened signals in NMR spectra. [c] The anti
isomer was not detected.
As expected, changing the alkyl length of guest 5a2+ does
not obviously change the dominance of 3-anti. But at least
three methylene groups are needed to ensure the formation
of the [1+1] macrocycle 3. For guests 5b2+–5g2+, compound
3-anti is always the predominant structure in the solution ac-
companied by small amount of 3-syn (for ROESY NMR and ESI-
MS experiments, see the Supporting Information, Figures S18–
S26). There also exists some unspecific structures for guests
5b2+–5c2+ and 5e2+–5g2+ as indicated by the broadened
peaks. Compound 5d2+ with two pentyl groups is still the
best template for the formation of 3-anti, although there is
also barely detectable 3-syn.
With these results, compound 3-anti seems to be very sensi-
tive to the bulkiness of the terminal groups when the central
alkyl group is long but not too long; however, 3-syn is stricter
to the central alkyl length and also requires two bulky groups
to prevent the formation of 3-anti. Guests 4d2+ and 5d2+ are
still the best templates for 3-syn and 3-anti, respectively.
Figure 5. a) Space-filling, and b) stick models of energy minimized structures
of 4d2+@3-syn and 5d2+@3-anti to show CꢀH···p and hydrogen-bonding
interactions. Hydrogen bonds are considered to exist when the distance
between O/N atoms and H atoms is smaller than 2.9 ꢁ. The butyl groups in
the hosts were shortened to methyl groups for viewing clarity.
bonds[32] were shown to be possible between the polarized
DABCO protons next to the quaternary ammonium and all the
four butoxyl oxygen and one of acetal oxygen atoms on dia-
ldehyde 1. For 5d2+@3-anti, CꢀH···O hydrogen bonds may
exist between DABCO methylene protons and the two butoxyl
oxygen atoms of 2. But CꢀH···N hydrogen bonds between
DABCO methylene protons and imine nitrogen atoms are also
possible. This is presumably due to that the DABCO of 5d2+ is
shallowly swallowed into the imperfect cavity of 3-anti and
thus CꢀH···N hydrogen bonds are possible. These hydrogen
bonds surely contribute to the high stabilities of 4d2+@3-syn
and 5d2+@3-anti.
To test the role of these hydrogen bonds, guests 9a2+–134+
(Figure 6a) have been synthesized. The DABCO heads in
guests 4d2+ and 5d2+ were first abbreviated to trimethyl qua-
ternary ammoniums to obtain guests 9a2+ and 10a+. Almost
all the hydrogen bonds in 4d2+@3-syn survive in the complex
of 9a2+@3-syn (the Supporting Information, Figure S29), and
thus 9a2+ still selectively and efficiently templates the
formation of 3-syn (Figure 6b and the Supporting Information,
Figures S30–S32). In contrast, half of hydrogen bonds in
5d2+@3-anti have been lost in the complex 10a+@3-anti (the
Supporting Information, Figure S29). Therefore, significant
amount of 3-syn and unspecified structures (broadened peaks)
were detected, although 3-anti is still the major structure (Fig-
ure 6b and the Supporting Information, Figures S33–S35).
Guests 9b2+ and 10b+ with triethyl ammonium end groups,
which are too flexible and bulky and hinder the formation of
hydrogen bonds, do not work as templates at all (the Support-
ing Information, Figure S36).
Influence of noncovalent interactions on the template effect
What kind of noncovalent interactions are responsible for the
high stabilities of 4d2+@3-syn and 5d2+@3-anti? Their space-
filling models (Figure 5a) both show that the alkyl protons of
the guests in the cavities may have CꢀH···p interactions[31] with
the naphthalene panels of the hosts. To confirm this, two
guests (62+ and 72+; Figure 6a) have been synthesized by re-
placing one or two methylene groups in guests 4d2+ and
5d2+ with oxygen atoms. Surprisingly, these two guests do
not template the formation of 3 (the Supporting Information,
Figure S27), suggesting the importance of CꢀH···p interactions
in the highly selective and efficient formation of both 4d2+@3-
syn and 5d2+@3-anti.
However, CꢀH···p interactions alone are not sufficient to sta-
bilize the complexes. Guest series 8 with six methylene groups
show no template effect at all in the equimolar mixture of
1 and 2 (the Supporting Information, Figure S28), suggesting
that the DABCO heads in 4d2+ and 5d2+ are not just steric
groups and should also get involved in the interaction with
the host.
Changing the charge states on 4d2+ and 5d2+ may also in-
fluence these CꢀH···O/N hydrogen bonds. Guest 11+ mimics
the effective binding site of 5d2+ except that only one positive
charge exists. When compared with 5d2+, although 3-anti is
still the predominant structure under the templation of 11+
(Figure 6b and the Supporting Information, Figure S37), a little
more unspecific structures exist, as indicated by the broadened
Careful analysis of the models 4d2+@3-syn and 5d2+@3-anti
reveals the possible existence of multiple hydrogen bonds
(Figure 5b) between DABCO and the oxygen or nitrogen
atoms of the host. For 4d2+@3-syn, the CꢀH···O hydrogen
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In short, the high stabilities of 4d2+@3-syn and 5d2+@3-anti
is due to the delicate balance and cooperation of multiple
noncovalent interactions between the hosts and the guests,
including but not limited to CꢀH···p, hydrogen bonding, and
cation···p interactions.
Guest-controlled reconfiguration
Besides guests 4d2+ and 5d2+, we found that guest 9a2+ is
also highly efficient and selective in the templated formation
of 3-syn. By assuming that free 3-anti and 3-syn have the same
stability and they can only interconvert with each other, com-
petition experiments may be used to crudely rank the relative
stabilities of 4d2+@3-syn, 5d2+@3-anti, and 9a2+@3-syn (the
Supporting Information, Figure S47). The results are 5d2+@3-
antiꢁ9a2+@3-syn <4d2+@3-syn. With this ranking, controlled
interconversion between 3-anti and 3-syn may be achieved by
controlling the addition sequence and stoichiometry of these
guests.
Figure 6. a) Chemical structures of guests 62+–16. The counterions of all the
guests are PF6ꢀ; b) Partial H NMR spectra (400 MHz, CDCl3/CD3CN=1:1,
1
Compound 4d2+@3-syn is much more stable than 5d2+@3-
anti. Addition of only 2 equiv 4d2+ into the solution of 5d2+
@3-anti can induce the complete reconfiguration of 3-anti into
3-syn (the Supporting Information, Figure S48). To achieve
a more sophisticated interconversion (Figure 7a), we can start
with 9a2+@3-syn (Figure 7b). The addition of 20 equiv of 5d2+
into this solution can almost completely convert 3-syn to 3-
anti (Figure 7c). The subsequent addition of 40 equiv of 4d2+
can efficiently switch 3-anti back to 3-syn (Figure 7d). Thus,
the reconfiguration sequence 3-syn!3-anti!3-syn can be
4.0 mm, 300 K) of the equimolar mixture of 1 and 2 in the presence of one
equivalent of guest 9a2+, 10a+, 11+, 122+, 142+, or 15+. The protons
colored in red and blue are assigned to the syn and anti isomers of 3,
respectively.
peaks at d=8.5 ppm and under other peaks. This may be at-
tributed to slightly weaker CꢀH···O hydrogen bonds caused by
only one positive charge. Thus, one may think that guest 122+
better mimics the effective binding site of 5d2+ and is at least
a better template than 11+. The experiments prove otherwise:
A significant amount of 3-syn and unspecified structures exist
(Figure 6b), indicating that 122+ is even a worse template than
11+. More dramatically, guest 134+ with more charges and
more acidic methylene protons is not just slightly worse than
guest 4d2+, and no clear templation was detected at all (the
Supporting Information, Figure S38). These counterintuitive re-
sults may be due to the non-selective and competitive binding
of mono-methylated DABCO by other library constituents,
suggesting that the high stabilities of 4d2+@3-syn and
5d2+@3-anti are the outcome of a delicate balance between
many parameters.
readily achieved by the sequential additions of guests 9a2+
,
5d2+, and 4d2+ in appropriate amounts (the Supporting
Information, Figure S49).
Conclusion
With dialdehyde 1, diamine 2, and organic guests 4d2+ and
5d2+, we have demonstrated that a complex dynamic combi-
natorial library can be transformed into a dynamic imine
macrocycle with a well-controlled configuration when using
appropriate guests as templates. Not only is the host constitu-
tion and configuration well controlled through the guest
templation, but also the orientation of the guest inside the
asymmetric cavity of the host is perfectly aligned. The different
templating outcomes of guests 4d2+ and 5d2+ on the host
configurations are attributed to the different shape and steric
complementarities between the guests and their correspond-
ing host isomers. Detailed studies reveal that these dynamic
covalent assemblies rely on the delicate balance and coopera-
tion of multiple noncovalent interactions between the host iso-
mers and the guest templates, including CꢀH···p, hydrogen
bonding, and cation···p interactions. Noncovalent templation
was demonstrated to be able to finely tune the structure of
dynamic covalent assembly at both the constitutional and con-
figurational levels. In addition, with judicious selection of
guests and rational design of the procedure, controlled recon-
figuration on artificial dynamic architectures without involving
constitutional changes has been achieved for the first time.
Until now, only guests with positive charges succeed in the
templated formation of 3, suggesting that cation···p interac-
tions[33] may likewise contribute to the high stabilities of 4d2+
@3-syn and 5d2+@3-anti. This is in line with the space-filling
models (Figure 5a). Presumably, the pyridinium cations should
also be good templates. Indeed, both guests 142+ and 15+ ef-
ficiently template the formation of [1+1] macrocycle (Fig-
ure 6b and Figures S39–S45), but the selectivity on the syn and
anti-configurations of 3 is not as good as that of 4d2+ and
5d2+, respectively. For guest 142+, a small amount of 3-anti
coexists with the predominance of 3-syn; however, for 15+, 3-
syn and 3-anti coexist in a ratio of approximately 1:1. But the
neutral analogue 16 of guest 15+ shows no template effect
(the Supporting Information, Figure S46), clearly indicating that
cation···p interactions contribute as well.
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Keywords: host–guest chemistry · macrocycles · noncovalent
interactions · self-assembly · template synthesis
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1
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Received: November 1, 2014
Published online on && &&, 2014
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FULL PAPER
Reconfigurable macrocycle: Both syn
and anti configurational isomers of an
imine macrocycle can be selectively ac-
cessible by using appropriate templates.
These two isomers can interconvert
through structural reconfiguration when
adding competing guests in appropriate
amounts (see figure).
&
Host–Guest Chemistry
Z. He, G. Ye, W. Jiang*
&& – &&
Imine Macrocycle with a Deep Cavity:
Guest-Selected Formation of syn/anti
Configuration and Guest-Controlled
Reconfiguration
Chem. Eur. J. 2014, 20, 1 – 9
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These are not the final page numbers! ÞÞ