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MOSC endo cavity. Such a steric effect was even more evident
when TMA+ was replaced by a series of related cationic
regulators, such as tetraethylammonium (TEA+), tetrapropy-
lammonium (TPA+), and tetrabutylammonium (TBA+). The
increasingly larger size of the cations led to growing sterics
that effectively cancelled out the positive electrostatic effect
and resulted in a gradual decrease of the reaction yield
(Supporting Information, Figure S5). As indicated above,
a similar steric effect was also implicated in the MOSC-
catalyzed reaction involving 2b.
To further pinpoint how the tetraalkylammonium cations
interacted with the MOSC, we obtained MOSC-1’, an
isomeric structure to MOSC-1, by replacing CoII with ZnII
in the synthesis (see the Supporting Information). The
diamagnetic nature of MOSC-1’ allowed us to use the NMR
spectroscopy to probe the ammonium binding of the MOSC
in CDCl3. In the absence of a guest, the 1H NMR spectrum of
MOSC-1’ featured broad and poorly separated peaks (Sup-
porting Information, Figure S6), which we attributed to the
MOSC molecules aggregating in the solution. While adding
the aldehydes or 2a did not improve the spectrum, the
addition of an excess amount of TBA+ to the solution led to
a drastically simpler spectrum with well-defined peaks
(Figure 2). The protons of one equivalent of TBA+ underwent
their faster motion in and out of the endo cavity (Supporting
Information, Figures S9–S11).[20]
The validation of molecular recognition occurring at both
the endo and exo sites underscored the exciting potentials
afforded by the trademark multi-pore architecture of the
MOSCs, and begged the intriguing question of whether the
exo binding event also contributed to regulating the catalysis.
Comparing the kinetic profiles of the reactions involving 1e,
2a, MOSC-1, and 0–9 equivalents of TMA+ indicated that the
reactivity was strongly influenced by the amount of TMA+
added (Supporting Information, Figure S12). Since there is
only one equivalent of TMA+ residing inside the endo cavity,
and additional TMA+ equivalents must be located outside the
substrate binding pocket, this finding suggested that the
MOSC-based catalyst system likely employed an unconven-
tional allosteric mechanism, in which electrostatic interac-
tions, instead of, or in addition to, conformational changes,
were used to regulate the catalysis.[7a,21]
In short, we successfully utilized a new class of container
molecules to harvest several trademark features of enzymatic
catalysis. We made use of two particularly important ele-
ments, namely selective substrate recognition and electro-
static/allosteric regulation, to switch on supramolecular
catalysis. The ability to demonstrate such biomimetic charac-
teristics in synthetic and non-aqueous systems has profound
implications for designing highly functional, complex, and
modular enzyme mimics. In particular, the viability to employ
task-specific small-molecule regulators to modulate chemical
reactions is anticipated to afford unprecedented opportunities
in asymmetric catalysis, photocatalysis, and other related
areas.
Acknowledgements
This research was supported by a National Science Founda-
tion CAREER Award CHE-1352279. Z.W., Y.Q., and J.L.
also acknowledge an NSF MRI Award CHE-1229035 for the
purchase of a Bruker 400 MHz NMR spectrometer.
Figure 2. 1H NMR spectrum of TBA+@MOSC-1’ in CDCl3. The molar
ratio of TBA+:MOSC-1’ is ca. 6.
a significant upfield shift, indicating its encapsulation inside
the endo cavity. The much larger up-field shift of a-protons
(Dd ꢀ 2.02 ppm), compared with that of d-protons (Dd
ꢀ 0.26 ppm), suggested that the positive charge of TBA+
was located deeper inside the binding pocket than its alkyl
ends, consistent with the proposed electrostatic mechanism.
The 1:1 binding ratio was verified by the Jobꢀs plot based on
a UV/Vis study of MOSC-1 (Supporting Information, Fig-
ure S7). The endo-capsulation of TBA+ by the MOSC was
Keywords: calixarenes · container molecules ·
Knoevenagel condensation · supramolecular catalysis ·
tetraalkylammonium
[1] a) C.-H. Wong, G. M. Whitesides, Enzymes in synthetic organic
chemistry, 1st ed., Pergamon, Elsevier Science Oxford, UK,
Tarrytown, N.Y., 1994; b) K. Drauz, H. Grçger, O. May, Enzyme
catalysis in organic synthesis: a comprehensive handbook, 3rd
ed., Wiley-VCH, Weinheim, 2012; c) A. M. Klibanov, Nature
[3] J. M. Lehn, Supramolecular Chemistry, Wiley, New York, 1995.
2011; c) J. M. Kang, J. Santamaria, G. Hilmersson, J. Rebek, J.
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unambiguously confirmed by a H–1H nuclear Overhauser
effect spectroscopy (NOESY) experiment (Supporting Infor-
mation, Figure S8). While the excess TBA+ did not show any
noticeable up-field shift, the NOESY spectrum revealed its
binding to the exo cavities.[19] Replacing TBA+ with TPA+,
TEA+, or TMA+ similarly improved the 1H NMR spectrum of
MOSC-1’, although it exhibited a strong dependency on the
cation size, as the smaller TEA+ and TMA+ gave rise to
a more complex NMR pattern, which is presumably due to
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Angew. Chem. Int. Ed. 2016, 55, 1 – 6
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