Angewandte Chemie International Edition
10.1002/anie.201709563
COMMUNICATION
Ercolani defined the expression: Kref·EM ≥ 185·n, (n being the
number of monomers in the cycle; n = 4), as the condition for
equally. For instance, we believe the reason why GC4 exhibited
a slightly anomalous behaviour in some of the experiments is
because of the presence of two consecutive aryl groups equipped
with alkoxy chains. This spacer was designed in this way in order
to keep the same symmetry as in the others, but rotation (for
instance) around the -bonds connecting these two units should
be considerably affected by the presence of the 4 neighbouring
alkyl chains. As a matter of fact, GC4 is the only compound that
did not assemble as cyclic tetramers at room temperature in THF
[5a,c]
quantitative cycle assembly at a given concentration.
We are
showing as horizontal dashed lines in Figure 4a the threshold
above which this condition is met for the three main solvents
studied herein: DMF, THF and CHCl
from Figure 2, this condition is (hardly) met by GC1 (4 -bonds)
in DMF, GC3 (8 -bonds) in THF and GC4 (10 -bonds) in CHCl
3
. As can also be deduced
3
.
Monomer GC5 (12 -bonds), on the contrary, is not able to cyclize
1
quantitatively in any of these solvents. Obviously, strengthening
(see H NMR in Figures S2A and S5B and CD spectra in Figure
S6A), thus deviating from the simulated trends displayed in Figure
2. Only lower temperatures (10 C; see Figure S5B) or more
5
-1 [11]
G:C association in apolar solvents (in toluene Kref > 10 M )
would allow GC5 and longer monomers to form quantitatively.
3 4
apolar environments (CHCl ) promoted cGC4 macrocyclization.
Another way of answering this question would be to estimate
for which monomer length the macrocyclization process becomes
endergonic, that is, the length at which cyclic species would not
be able to compete at all with linear oligomers, independently of
the concentration. Figure 4b displays the G° values of the
cyclotetramerization process, calculated in THF either via G =
In short, we have analyzed the effect of monomer lenght on a
supramolecular ring-chain equilibrium. The extrapolation of our
trends afforded an estimation on how large we can build a cyclic
assembly in competition with linear oligomers. The quantitative
results obtained in this work only apply to our particular monomer
structure, but the analysis performed and our general conclusions
could in principle be extended to many supramolecular cycles or
cages in which size is tuned.[12] Thus, a careful design of the
respective building blocks, linking motifs, and the substituents that
confer solubility must be carried out to limit the number of degrees
of freedom that are lost upon cyclization, so that the desired
supramolecular structure can be assembled with high fidelity.
H-TS (from the variable temperature NMR experiments; Figure
S5B) or via G = -RT ln K (from the NMR dilution experiments;
T
Figure S2A), which show a satisfactory match. The extrapolation
to G° = 0 indicates that the cyclotetramerization process
becomes energetically unfavourable in THF when the number of
1
-bonds in the spacer reaches ca. 26, which would correspond to
2 phenylene-ethynylene units. Again, this analysis strongly
depends on Kref, which can be tuned by the solvent employed.
Reinforcing H-bonding strength in CHCl would make this number
3
higher, while decreasing it in DMF would make it lower. In fact,
Figure 2 shows that GC5, with 12 -bonds, would be unable to
cyclize in DMF independently of the concentration, and only linear
oligomers are formed in the high concentration regime.
Acknowledgements
Funding from the European Union (ERC-Starting Grant 279548)
and MINECO (CTQ2014-57729-P) is gratefully acknowledged.
Keywords: Supramolecular Chemistry • Noncovalent Synthesis
•
Chelate Effect • Nucleoside Self-assembly • Effective Molarity
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Figure 4. Plots of (a) Ln EM vs number of σ-bonds for GC1-GC5 in THF (green
[
3]
4]
M. I. Page, Chem. Soc. Rev. 1973, 2, 295-323.
circles) and CHCl
which the Kref·EM ≥ 185·n condition is met for DMF, THF and CHCl
3
(blue squares). Dashed lines show the threshold above
. (b) ΔH,
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The analysis made herein is of course only applicable to our
particular monomer structure and binding interaction. Any change
to the repeating unit in the central spacer may lead to important
deviations. We are also ignoring the influence of the lateral alkyl
chains in the spacers, which had to be installed due to synthetic
and solubility reasons. The length and relative position of these
chains can influence the moments of inertia around -bonds and
introduce diverse local solvation, conformational and steric effects
that make that not all -bonds in the spacer rotate and bend
2
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