Crystal Growth & Design
Article
calixarene capsules are packed in an antiparallel configuration
(Figure 2B). The encapsulation of the guest molecule in the
calixarene pocket perturbed the customary quasi-hexagonal
hydrogen bond motif found in the guest-free structure (Figure
3). A singular common feature of guest-free G4SC and G1.5SC
guanidinium-sulfonate hydrogen bonds that ordinarily com-
plete the GS sheet.
The deficiency of guanidinium ions in G1.5SC ⊃ Δ1-pyrroline
suggests the presence of other countercations to balance the
four negative charges of the 4-sulfocalix[4]arene anion.
Refinement of the crystal structure found only one water
molecule per 4-sulfocalix[4]arene anion, associated through
hydrogen bonding with one of the sulfonate groups.
Thermogravimetric analysis (TGA) upon heating to 200 °C,
however, revealed a mass loss corresponding to approximately
five equivalents of water in the crystal and one equivalent of Δ1-
pyrroline (Figure S9 of the Supporting Information). The
NMR data did not reveal any species other than water and no
other source of cations was present in the crystallization
medium, arguing for charge compensation by hydronium ions
in the crystal lattice. This was supported by the observation that
15 mg G1.5SC ⊃ Δ1-pyrroline crystals in 1 mL of water afforded
acidic solutions with pH = 2 (the calculated pH based on 2.5
equivalents of hydronium is 1.5), whereas the pH for the guest-
free compound was nearly neutral (pH = 6).
In accordance with previous reports,4 the Δ1-pyrroline
monomer is stable in DMSO for the four days and even less
in aqueous solution. The intensities of the original NMR peaks
declined noticeably over four days in D2O. Upon standing at
ambient temperature in D2O for two weeks, the characteristic
NMR peaks for both monomer and trimer were no longer
observed, due to polymerization. The pure liquid pheromone
gradually converts to a dark solid because of polymerization
after four months storage in neat liquid form. In contrast, the
monomer can be stored indefinitely in the G1.5SC framework
with no decomposition evident from NMR, IR, and single
crystal X-ray data. This illustrates that polymerization of the
otherwise unstable Δ1-pyrroline monomer was prevented by its
sequestration in the solid state. Moreover, crystals of G1.5SC ⊃
Δ1-pyrroline become opaque within ten minutes upon standing
in open air. TGA revealed that all the lattice water was lost
within 10 min at 30 °C. Upon further heating of the remaining
solid, Δ1-pyrroline exits the solid at ∼40 °C. When sealed in
humid air, however, the crystals were stable indefinitely.
1H NMR spectroscopy revealed that the equilibrium between
the Δ1-pyrroline monomer (M) and its trimer (T) is achieved
immediately upon adding the pheromone to an aqueous
solution. The equilibrium constant at ambient temperature
(298 K) was Keq = 1.3 × 10−2 M2, calculated from [M]:[T] =
Figure 3. (A) Hydrogen bond motif of guest-free G4SC. G ions
bridging three sulfonates at the upper rim of each 4-sulfocalix[4]arene
are depicted as yellow balls-and-sticks. G ions bridging three sulfonates
on two neighboring sulfocalixarenes are depicted as green balls-and-
sticks. G ions bridging three sulfonates on three neighboring
sulfocalixarenes are depicted as spacefilled. (B) Hydrogen bond
motif of G1.5SC ⊃ Δ1-pyrroline.
1
1.0:0.6 from integration of the monomer and trimer H NMR
1
⊃ Δ1-pyrroline is the presence of G ions, bridging three
sulfonate groups on three neighboring calixarenes, a natural
consequence of the 3-fold symmetry of the G ion (Figure 3,
depicted as spacefilled). These G ions define a rhombus with
dimensions of 14.0 × 14.0 Å, reflecting a significant expansion
compared with guest-free G4SC, in which the G ions define a
parallelogram with dimensions of 12.5 × 14.2 Å, suggesting an
expansion of the 2D sheet. The G ions that otherwise cap the
top rim of the calixarene in guest-free G4SC (Figure 3, yellow
ball-and-stick) are absent, their positions occupied by the
encapsulated Δ1-pyrroline. Inclusion of the Δ1-pyrroline guest
also distorts the calixarene (S−S distances of 6.98 Å and 7.35 Å
on the upper rim compared with the guest-free values of 6.96
and 7.08 Å), which frustrates incorporation of a G ion at a third
site occupied in guest-free G4SC (Figure 3, green ball-and-
stick). The absence of a G ion at the upper rim of the calixarene
illustrates that the binding of the Δ1-pyrroline guest by the
calixarene is sufficiently strong to overcome the loss of
peaks. Variable temperature H NMR revealed that the [M]:
[T] ratio increased with increasing temperature (ΔS = +313 J
mol−1 K−1). Upon addition of one equivalent of G4SC to a 0.06
M (based on monomer) aqueous solution of the pheromone,
the NMR peaks assigned to the monomer and trimer shifted
upfield, consistent with association of both species with the
calixarene pocket and in agreement with the 1H NMR spectrum
observed for dissolved crystals of G1.5SC ⊃ Δ1-pyrroline (see
above). No free pheromone, in either the monomer or the
triplet form, was apparent. This illustrates that the calixarene
binds the monomer and trimer equally well in the solution
phase. During crystallization, however, only the monomer is
encapsulated due to the prohibitive size of the trimer (Figure
4).
These observations illustrate the separation of an active
pheromone monomer from its inactive trimer form through
sequestration in an appropriately sized molecular capsule in a
solid-state framework, adding to emerging discoveries that
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dx.doi.org/10.1021/cg4005906 | Cryst. Growth Des. XXXX, XXX, XXX−XXX