Molecular marriage through partner preferences in covalent cage formation and cage-to-cage transformation

Article abstract of DOI:10.1021/ja310083p

Unprecedented self-sorting of three-dimensional purely organic cages driven by dynamic covalent bonds is described. Four different cages were first synthesized by condensation of two triamines and two dialdehydes separately. When a mixture of all the comp

Full text of DOI:10.1021/ja310083p

Communication
pubs.acs.org/JACS
Molecular Marriage through Partner Preferences in Covalent Cage
Formation and Cage-to-Cage Transformation
Koushik Acharyya, Sandip Mukherjee, and Partha Sarathi Mukherjee*
Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560012, India
S
* Supporting Information
Chart 1
ABSTRACT: Unprecedented self-sorting of three-dimen-
sional purely organic cages driven by dynamic covalent
bonds is described. Four different cages were first
synthesized by condensation of two triamines and two
dialdehydes separately. When a mixture of all the
components was allowed to react, only two cages were
formed, which suggests a high-fidelity self-recognition. The
issue of the preference of one triamine for a particular
dialdehyde was further probed by transforming a non-
preferred combination to either of the two preferred
selectivity (one specific combination) when a mixture of the
combinations by reacting it with the appropriate triamine
two triamines and one dialdehyde was used. Moreover, in a
or dialdehyde.
more complex situation, when all four components were
allowed to react, they produced only two of the cages that were
formed in the previous experiment. In other words, they
combined with their preferred partners. To further establish
ature, especially in biological systems, utilizes self-sorting
Nto achieve “order out of chaos” by discriminating “self”
these partner preferences, we show that a non-self-sorted cage
from “non-self” in a complex reaction mixture. Self-sorting has
the ability to reduce the number of components by arranging
into specific high-fidelity combinations.1 In abiological systems,
non-covalent self-sorting, especially hydrogen-bonding and
donor−acceptor interaction driven self-recognitions, has been
widely explored.2 Lehn, Stang, and others have reported
examples of self-recognition based on dynamic coordination-
driven self-assembly.3,4 Very recently, a few examples have
come up in which dynamic covalent bonds have been utilized
along with metal−ligand coordination to construct self-sorted
hybrid macrocycles and cages.5 In contrast, though there are
quite a few reports in the literature of self-sorted organic
macrocycles, purely organic self-sorted 3D architectures have
not been studied.
could be transformed to either one of the self-sorted cages by
allowing it to react with the appropriate triamine or dialdehyde.
These transformations become viable because the bonds that
assemble the components together (namely, the imine bonds)
are dynamic in nature. Thus, the preferred combination of
components can form in solution, even though we started from
a non-preferred combination.
Nanoscopic organic cages A3X2, A3Y2, B3X2, and B3Y28 were
synthesized (Supporting Information) by condensing 2 equiv of
flexible triamine (X or Y) with 3 equiv of dialdehyde (A or B)
in CHCl3−EtOH (1:10). Products were fully characterized by
1H NMR, 13C NMR, COSY, HMQC, FTIR, and ESI-MS.
These results confirmed the formation of 3:2 (dialdehyde:tri-
amine) self-assembled cages through imine bond formation in
all cases.
Purely organic three-dimensional cages can be synthesized
utilizing dynamic covalent bond (such as imine bond)
formation to avoid tedious multistep reactions. These porous
cages have attracted much attention recently, and many of them
have been utilized for various functions, such as sensing, gas
storage and separation, catalysis, and drug delivery.6,7 The
dynamic bonds may potentially allow self-sorting in multi-
component systems, generating specific cages of intended
multiple functionalities. This would also allow cage-to-cage
transformations in solutiona very useful feature that can be
utilized to change the cage system (in situ) when necessary.
Here, we report one such attempt with two dialdehydes [A =
1,3-bis(4-formylphenylethynyl)benzene, B = bis(4-
formylphenyl)methane] and two triamines [X = 1,3,5-tris-
(aminomethyl)-2,4,6-trimethylbenzene, Y = tris(2-aminoethyl)-
amine], which were found to form four cages (Chart 1) when
treated separately in pairs but showed remarkable partner
We were also able to crystallize the cage B3X2 from its
chloroform solution by n-pentane vapor diffusion as 2-
(B3X2)·7.5CHCl3. As expected, the crystal structure confirmed
the 3:2 self-assembled structure of this cage. Interestingly, the
asymmetric unit contains two cage molecules along with several
CHCl3 molecules situated both inside and outside the cage
molecules. The cage is roughly ellipsoidal in shape. The
distance between the centroids of the benzene rings of the
triamine parts is ∼14 Å, which can be defined as the length of
the cage (Figures 1a and S24).
The three methylene carbon atoms at the central part of the
cage form roughly equilateral triangles of length ∼12 Å. As
expected, all the imine bonds are trans in nature. However, the
Received: October 12, 2012
© XXXX American Chemical Society
A
dx.doi.org/10.1021/ja310083p | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
CHCl3−EtOH (1:10 v/v) at room temperature for 24 h
1
(Scheme 2). Despite the innumerable possibilities, H NMR
and ESI-MS (Figures 2 and S18) analyses of the precipitated
mixture revealed the exclusive formation of cages A3Y2 and
B3X2. 1H NMR monitoring of the reaction shows that
characteristic peaks corresponding to aldehydes A and B
completely vanished, and peaks corresponding to cages A3Y2
and B3X2 arose during the reaction. In the initial stage of the
transformation, there were several intermediate byproducts, as
1
indicated by H NMR. Those intermediates were gradually
consumed, leading to the formation of two specific
combinations among the myriad possibilities; in other words,
self-sorting is observed.
All four cages are sparingly soluble in the solvent mixture
[CHCl3−EtOH (1:10)] used for the self-sorting experiment, so
the self-sorting may be a result of the faster precipitation of two
of the cages (A3Y2 and B3X2) as compared to the other two
(A3X2 and B3Y2). In other words, the self-sorting may be
precipitation induced.9
Figure 1. (a) Ball-and-stick diagram of the single-crystal X-ray
structure of B3X2. Hydrogen atoms and solvent molecules (CHCl3)
have been removed for clarity. (b) Energy-optimized [DFT, B3LYP]
structure of B3X2.
cages lack C3 symmetry, as the three arms are not equivalently
disposed in space. The energy-optimized (DFT, B3LYP, 631-
G) structures of all four cages show them to be ellipsoidal in
shape (lacking C3 symmetry), with all the imine bonds in trans
disposition (Figure S27), much like the crystal structure of
B3X2. In fact, the molecular dimensions of the cage B3X2 in its
crystal structure and energy-optimized geometry are remarkably
similar (Figures 1b, S24, and 25). This also encouraged us to
use these optimized structures and their energies as a guide to
calculate theoretically the heats of the reactions as described
later.
After the four cages were synthesized, the first question that
came to our minds was, what would happen if two triamines (X
and Y) and one dialdehyde (A or B) were present in the same
reaction mixture? To address this, two sets of experiments were
carried out with two triamines and one aldehyde. In a typical
experiment we treated 3 equiv of B with a mixture of 2 equiv of
X and 2 equiv of Y in CHCl3−EtOH (1:10) at room
temperature with stirring for 48 h. The precipitate that formed
during the course of the reaction was washed with ethanol and
characterized by NMR. Surprisingly, 1H NMR showed exclusive
formation of cage B3X2 (Scheme 1). Thus, aldehyde B was
found to select X as its preferred partner, although Y was also
present in the solution in an equivalent amount. In contrast,
aldehyde A under similar conditions displayed a remarkable
preference for triamine Y over triamine X and led to the
exclusive formation of cage A3Y2 (Scheme 1).
To investigate this possibility, the reaction rates of individual
cage formations need to be probed, but complexities due to
precipitation make any such rate constant determination
unreliable for this solvent system [CHCl3−EtOH (1:10)].
However, the cages are soluble in chloroform. Still, the exact
rate laws could not be established due to the complexity
(several uncharacterized intermediates) of the reactions. So to
get a glimpse of the reaction kinetics, the individual cage
formations were monitored in CDCl3 for a fixed period of time.
It was found that within 5 h the conversion of the individual
pairs of reactants to the cages A3X2, A3Y2, B3X2, and B3Y2 was
respectively 19%, 97%, 17%, and 78%. These experimental
results suggested that cages A3Y2 and B3Y2 exhibit faster self-
assembly kinetics. However, when the four-component self-
sorting experiment was carried out in CDCl3 (monitored by 1H
NMR up to 130 h, Figure S21), again only A3Y2 and B3X2
could be detected. So, the same two cages are self-sorted in
both solvent systems. This result demonstrates that precip-
itation, if any, has little effect. It is also evident that the reaction
rates alone cannot explain the outcome of self-sorting in
chloroform. So, we performed theoretical calculations to get
some insight into the energetics of these reaction processes.
Solvent effects and entropy play major roles in these
reactions. However, it is very difficult to calculate theoretically
the energetics of these reactions taking these factors in account.
A compromise can be achieved by calculating the energy
differences between the reactants (2 mol of triamine + 3 mol of
dialdehyde) and the products (1 mol of the cage + 6 mol of
water). This process can provide rough estimates of the heats of
the reactions (ΔHr). The optimized energies of the
components involved were obtained through DFT (B3LYP,
Naturally, the next question that arise from these findings is,
would similar selectivity still be observed in a more complex
mixture of all four components (X, Y, A, and B)? If so, then the
system can be defined as a self-sorting system of four
components. This kind of self-sorting of purely organic cages
has so far not been explored in the literature. To address this
new question, we allowed a solution of triamines X and Y to
react with a mixture of dialdehydes A and B (ratio 2:2:3:3) in
Scheme 1
B
dx.doi.org/10.1021/ja310083p | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
Scheme 2
to a self-sorted cage (preferred marriage) by exchanging either
component in solution.
Cage B3Y2 (1 equiv) was allowed to react with dialdehyde A
(3.5 equiv) in CDCl3, which led to complete conversion to cage
A3Y2 (Scheme 3) within 30 h at room temperature with the
Scheme 3
Figure 2. 1H NMR of the precipitated mixture of products of the self-
sorting experiment and the individual cages recorded in CDCl3.
631-G) calculations.10 All calculated heats of reactions were
found to be positive, illustrating the crucial role played by the
positive entropy changes in the cage formations. The heats of
reactions range from 40 to 50 kcal/mol. According to these
calculations, the formation of A3Y2 is slightly more energy
demading than that of A3X2 (∼2.3 kcal/mol). The calculations
also revealed that the formation of B3Y2 is much more energy
demanding (∼5.9 kcal/mol) than that of B3X2. Therefore, A3Y2
and B3Y2 are energetically unfavored (but they form faster in
solution). The self-sorting process can be thought to be two
parallel reactions, with the reactants for each reaction selected
by nature as preferred partners. If the overall process were
kinetically controlled, a mixture of products dominated by A3Y2
and B3Y2 (as their rates of formation are considerably higher)
would be expected. So, the self-sorting must be thermodynami-
cally controlled, which can explain the formation of B3X2. The
formation of A3Y2 is probably forced by the resulting
unavailability of B and X. In addition, A3Y2 is only very slightly
more energy demanding than A3X2 (shortcomings of the
theoretical calculations regarding solvent and entropy effects
must also be kept in mind). It is evident from the theoretical
calculations that, in a mixture of B, X, and Y, the
thermodynamically preferred product is B3X2. The addition
of A to this mixture helps the equilibrium by removing Y from
the solution (very fast), resulting in the overall thermodynamic
preference for B3X2 and A3Y2. These results point to the well-
known fact that, in self-sorting, collective behavior may not
always reflect the conclusions drawn from studies on individual
components or reaction system in isolation.1
Figure 3. 1H NMR spectra recorded over time during the
transformation of cage B3Y2 to cage A3Y2 in CDCl3, with spectra of
the pure components involved for comparison. Peaks indicated by
different symbols were used for monitoring the reaction progress.
1
release of B (Scheme 3). H NMR monitoring (Figure 3)
revealed that, during the course of the transformation,
characteristic aromatic peaks corresponding to cage B3Y2, at δ
= 7.03 and 7.18 ppm, completely vanished with the arrival of
new characteristic peaks assigned to aromatic protons of cage
A3Y2, at δ = 6.76 and 8.01 ppm. Furthermore, ESI-MS analysis
of the final reaction mixture also confirmed the formation of
cage A3Y2 along with the presence of aldehyde B (Figure S22).
In a similar manner, when the cage B3Y2 was treated with
amine X, cage conversion took place within 115 h (Scheme 3).
1
Formation of cage B3X2 was similarly confirmed by H NMR
(Figure S20) and ESI-MS (Figure S23) analyses. In a similar
way, conversion of A3X2 to A3Y2 was very facile, though the
reverse was not feasible. To the best of our knowledge, this
represents the first example of cage-to-cage transformation
involving purely organic imine-based assemblies.
To summarize, we were able to show, for the first time, the
self-sorting behavior of a mixture of two different triamines and
The dynamic nature of the reaction system as well as the
high-fidelity self-sorting should effect a cage-to-cage trans-
formation. A non-self-sorted cage system (a non-preferred
marriage of a triamine and a dialdehyde) is expected to convert
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Journal of the American Chemical Society
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ASSOCIATED CONTENT
* Supporting Information
Synthetic and characterization data (NMR, FTIR, ESI-MS),
crystallographic details for the cage B3X2, details of the DFT
calculations, and single-crystal X-ray data for B3X2 in CIF
format. This material is available free of charge via the Internet
at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
psm@ipc.iisc.ernet.in
Notes
■
Am. Chem. Soc. 2011, 133, 6650. (i) Mateus, P.; Delgado, R.; Brandao,
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P.; Felix, V. J. Org. Chem. 2012, 77, 6816. (j) Alberto, R.; Bergamaschi,
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M. Chem. Commun. 2012, 48, 9861. (l) Kumar, R.; Guchhait, T.; Mani,
G. Inorg. Chem. 2012, 51, 9029.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
K.A. and S.M. gratefully acknowledge the CSIR, New Delhi,
India, for Research Fellowships. The authors are grateful to Mr.
Sanjoy Mukherjee for help in the theoretical calculations. The
authors also thank the DST, India, for research grant.
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