Consequences of cooperativity in racemizing supramolecular systems

Article abstract of DOI:10.1002/anie.201201701

Saluting the sergeant: Phg-BTA (see scheme) cooperatively self-assembles into helical aggregates and shows unprecedented racemization behavior in the presence of base. In thermodynamically controlled conditions, the addition of a small amount of chiral auxiliary to this mixture results in a deracemization reaction and a final enantiomeric excess of 32 %. A theoretical model is presented to understand in detail the results obtained. Copyright

Full text of DOI:10.1002/anie.201201701

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DOI: 10.1002/anie.201201701
Supramolecular Systems
Consequences of Cooperativity in Racemizing Supramolecular
Systems**
Seda Cantekin, Huub M. M. ten Eikelder, Albert J. Markvoort, Martijn A. J. Veld,
Peter A. Korevaar, Mark M. Green, Anja R. A. Palmans,* and E. W. Meijer*
Racemization, an irreversible process arising from the
reversible interconversion of enantiomers,[1] is governed by
simple first-order kinetics.[2] Racemization can occur under
a variety of conditions and is associated with the disappear-
ance of optical activity.[1] On the other hand, the conversion of
a racemic mixture into an excess of one enantiomer,
deracemization, is useful to yield nonracemic products out
of a racemic mixture without the intermediate separation of
materials.[3] In the examples of deracemization, chiral auxil-
iaries are used to favor the nonracemic product: such as chiral
catalysts in dynamic kinetic resolutions[4–7] or chiral host–
guest interactions.[8,9] More recently, attrition-enhanced Ost-
wald or Viedma ripening was used to obtain enantiomerically
pure crystals from racemic mixtures, in which the preference
of the handedness is determined by chiral external forces,
including chiral seeds.[4,10–14] Herein we present a supramolec-
ular system based on cooperative self-assembled helicity,
which exhibits strong chiral amplification and in which
racemization and deracemization processes are in thermody-
namic equilibrium and take an unprecedented form.
helical supramolecular polymers in solution and show strong
majority-rules behavior.[15–18] In a system under majority-rules
control, the major enantiomer dictates the helical sense of the
supramolecular polymer to which the minor enantiomer
adjusts. This unique behavior results in a strong nonlinear
relationship between the optical activity of the supramolec-
ular polymer and the overall enantiomeric excess (ee), which
were described and quantified by one-dimensional Ising
models adapted from the theory of covalent helical poly-
mers.[19] Recently, we introduced a novel method for quanti-
fying chiral amplification in a two-component self-assembling
BTA system by taking into account the dynamic equilibrium
between free monomers and the supramolecular polymer and
the cooperative growth of the corresponding polymer.[20,21]
Our method is based on a common reaction scheme in which
supramolecular polymerization is described as a sequence of
stepwise monomer addition and dissociation events. In this
model, the equilibrium concentrations of the BTA molecules
in the free monomer state and in the aggregated state are
predicted as a function of the overall ee value by solving the
mass–balance equations for the enantiomeric monomers.[20]
Calculations indicate that the majority-rules behavior in
BTA-based supramolecular polymers leads to a nonlinear
change in the concentration of enantiomeric free monomers
as a function of the overall ee value under the conditions at
which BTA monomers are mostly aggregated. In other words,
the ee value of the enantiomeric units participating in the
aggregate differs from the ee value of the free enantiomeric
molecules in the solution except at an ee value of either 0 or
100%. Similar nonlinear effects have been shown in asym-
metric catalysis and were reported by Kagan and co-work-
ers.[22,23]
In earlier work, we showed that enantiomeric N,N’,N’’-
trialkylbenzene-1,3,5-tricarboxamide (BTA) molecules form
[*] S. Cantekin, M. A. J. Veld, P. A. Korevaar, Dr. A. R. A. Palmans,
Prof. Dr. E. W. Meijer
Institute for Complex Molecular Systems
Laboratory of Macromolecular and Organic Chemistry
Eindhoven University of Technology
P.O. Box 513, 5600 MB Eindhoven (The Netherlands)
E-mail: a.palmans@tue.nl
e.w.meijer@tue.nl
Dr. H. M. M. t. Eikelder, Dr. A. J. Markvoort
Biomodeling and Bioinformatics Group, Institute of Complex
Molecular Systems, Eindhoven University of Technology
P.O. Box 513, 5600 MB Eindhoven (The Netherlands)
Inspired by these predictions, herein we superimpose on
this system racemization of the participating enantiomers and
elucidate the effects of cooperativity on reaction kinetics and
the nature of the final state. We have adapted the BTA
structure to allow racemization by incorporating phenyl-
glycine octyl ester units. The phenylglycine units were
selected because they racemize in solution upon the addition
of the base 1,8-diazabicycloundec-7-ene (DBU)[11] (Figure 1).
Herein we extend the two-component model describing the
majority-rules system to a racemizing system. We find that the
model is capable of a precise quantitative description of the
experimental data we obtained. In addition, we introduce
a new three-component model to explain why racemization
reactions of cooperatively self-assembled BTAs result in
deracemization in the presence of a chiral additive.
Prof. Dr. M. M. Green
Department of Chemical and Biological Sciences
Polytechnic Institute of New York University
Brooklyn, NY 11201 (USA)
[**] This work was supported by the NRSC-C foundation and the
Netherlands Organization for Scientific Research (Spinoza-NWO).
The effort at the Polytechnic Institute of New York University was
supported by the National Science Foundation of the U.S. We thank
L. L. J. van Dongen and X. Lou for assistance with chiral HPLC, B.
Boetzkes for assisting with the initial experiments, P. J. M. Stals for
providing compounds (R)-2 and (S)-2, T. F. A. de Greef for intrigu-
ing discussions, and K. Pieterse for the background picture in the
Table of Contents.
Supporting information for this article (experimental details) is
available on the WWW under http://dx.doi.org/10.1002/anie.
201201701.
We synthesized phenylglycine octyl ester-substituted
N’,N’’-dioctyl-N-[(phenyl)octyloxycarbonylmethyl]benzene-
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ence between the fraction of M- and P-type helical aggregates
(net helicity = ([P]ꢁ[M])/([P] + [M])). The origin of this
nonlinear behavior is explained by a theoretical model[20]
for a two-component self-assembling BTA system (see
Supporting Information for details). In this model, the two
enantiomers can aggregate into supramolecular polymers
with two types of helicity, in which the favorable enthalpy of
elongation (DH8e) is reduced by
a
mismatch penalty
[20]
(DH8mm
)
when a monomer ((R)-1 or (S)-1) assembles into
its nonpreferred helical sense. The value of this mismatch
penalty can be obtained from the majority-rules experiment
described in Figure 2a and is equal to ꢁ1.7 kJmolꢁ1 for this
system (Figure S13).
In Figure 2b, the concentrations of the enantiomeric units
inside and outside of the aggregates as predicted by this
model are presented as a function of the ee value (along the x-
axis). The y-axis in Figure 2b gives the predicted concen-
trations of the monomers that are not in the supramolecular
polymer. According to this two-component model, two
regimes, separated by a certain critical ee value (eecr), can be
distinguished. In the first regime, the absolute value of ee is
less than eecr (j ee j< eecr) the free monomer concentrations of
both enantiomers (Figure 2b, red and blue lines; i.e. those not
participating in the aggregate) have a weak dependence on
ee value and are almost equal, with a slight excess for the
major enantiomer. For the second regime, in which j ee j> eecr,
the free monomer concentration of the major enantiomer
increases whereas the free monomer concentration of minor
enantiomer decreases (moving to the right along the x-axis),
leading to a large difference between the concentrations of
the enantiomers in the free monomer state as the overall
ee value increases. On the other hand, the concentrations of
the enantiomeric units within the aggregated state, the
supramolecular polymers, change as seen in the graph at the
right within Figure 2b. For the first regime, in which j ee j<
eecr, the number of units entering the major helical sense is
increasing (moving to the right along the x-axis). Both
enantiomeric units enter this major aggregate from the
solution, while the number of units entering the minor helical
sense decreases linearly until the minor aggregate does not
exist at eecr. A detailed interpretation of Figure 2b is given in
the Supporting Information (Section 13c).
Now we turn our attention to the experimental conse-
quences of adding a racemization reaction to this system. We
investigated the racemization reaction of (S)-1 molecules
upon addition of DBU (1 equiv) in MCH. At 808C, under the
conditions at which almost all (S)-1 and (R)-1 monomers are
in the molecularly dissolved state (cfreemonomer ꢂ 9 ꢀ 10ꢁ4 m),
complete racemization (ee = 0%) is reached within 3 h (Fig-
ure 2c). The racemization reaction follows first-order reac-
tion kinetics, that is, the natural logarithm of the ee value
changes linearly as a function of time (Figure 2c, inset).
However, at 208C when (S)-1 molecules are almost fully
aggregated and only relatively few free monomers (cfreemonomer
ꢂ 6 ꢀ 10ꢁ6 m) are present in solution, the racemization process
proceeds extremely slowly and shows a remarkable and
unprecedented deviation from first-order reaction kinetics
(Figure 2d). Although the effect of temperature on the
reaction rate is inevitable, the unusually slow racemization
Figure 1. a) Molecular representations of N’,N’’-dioctyl-N-[(phenyl)-
octyloxycarbonylmethyl]benzene-1,3,5-tricarboxamide (Phg-BTA, 1).
Racemization takes place upon addition of DBU in MCH. b) Schematic
representation of Phg-BTA-based supramolecular polymers.
1,3,5-tricarboxamide (Phg-BTA) in both enantiomeric forms,
(R)-1 and (S)-1 (ee value of about 82% for each, as
determined by chiral HPLC; see Supporting Information
for details, Figures S1–S10). Similar to alkyl-substituted BTA
analogues,[24,25] the enantiomers of Phg-BTA form helical
supramolecular polymers by means of strong threefold
intermolecular hydrogen bonding in methylcyclohexane
(MCH) solution in a cooperative fashion (c = 1.2 mm, De =
ꢀ 38 Lmolꢁ1 cmꢁ1 at 223 nm at 208C determined for ee >
97%). The (S)-enantiomer forms right-handed (P) helical
supramolecular polymers while the (R)-enantiomer forms
left-handed (M) helical supramolecular polymers (Fig-
ure 1b). The mechanism of formation of these supramolec-
ular polymers and their preferred handedness are detected by
UV/Vis spectroscopy and circular dichroism (CD) spectros-
copy. The thermodynamic parameters characterizing the self-
assembly mechanism, such as the enthalpy of elongation
(DH8e), the entropy of elongation (DS8e), and the nucleation
penalty (DH8nuc), are obtained by fitting the temperature-
dependent data with the theoretical model (Figure S11). The
average number of monomers in a supramolecular polymer
was calculated to be 168 with an ee value of 100% under the
conditions applied (Figure S12).
Phg-BTA-based supramolecular polymers show majority-
rules behavior when the two enantiomers are mixed in
varying ratios. The mixing experiment results in a nonlinear
change in the net helicity as a function of the ee value
(Figure 2a). The ee value is defined as the difference between
the total concentrations of enantiomeric Phg-BTAs
added to the solutions (ee = ([(S)-1]ꢁ[(R)-1])/([(S)-1] +
[(R)-1])x100%) and the net helicity is defined as the differ-
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Figure 2. a) Net helicity as a function of the ee value obtained from the majority-rules experiment by mixing solutions of (S)-1 and (R)-1
(c=1.2 mm in MCH) at 208C (the line is to guide the eye). The net helicity is calculated by dividing De at every ee value by 38 Lmolꢁ1 cmꢁ1, which
is the maximal attainable value for De. b) Computed concentrations of free (S)-1 and (R)-1 monomers in solution as a function of ee value at
208C (ctot =1.2 mm). Graph on right: concentration of the monomers in the P and M type supramolecular polymers ([MP]) as a function of
ee value at 208C. The calculations are based on the majority-rules experiments and by using the thermodynamic parameters;
DH8mm =ꢁ1.7 kJmolꢁ1, DH8e =ꢁ72.4 kJmolꢁ1, DH8nuc =ꢁ12.2 kJmolꢁ1, DS8e =ꢁ0.15 kJmolꢁ1 Kꢁ1. c) Racemization of (S)-1 in the presence of
DBU (1 equiv) in MCH (ctot =1.2 mm) at 808C, monitored by chiral HPLC. Inset: natural logarithm of ee value as a function of time with
corresponding fit for first-order reaction kinetics (black line). d) Racemization of (S)-1 upon addition of DBU (1 equiv) in MCH (ctot =1.2 mm) at
208C (red dots) with predicted ee values using k=0.517 hꢁ1 over time (black line). Graph on right: natural logarithm of ee value as a function of
time with the corresponding fit for the first-order reaction kinetics (black line).
rate cannot be explained by the change in temperature only.
We propose that the racemization kinetics at low temperature
arises because only free monomers, those outside the
aggregate, can racemize. Furthermore, the shape of the
curve for the ee value as a function of time at 208C suggests
that the racemization of Phg-BTA can be described by two
distinct kinetic regimes; one regime (j ee j> eecr) has a faster
rate than the other (j ee j< eecr). The ee value at the interface
between the two regimes correlates with the eecr shown in the
majority-rules experiment. Similar two-rate kinetics was
reported previously for the racemization of asparagine.[26] It
was suggested that asparagine hydrolyses into aspartic acid
during the racemization reaction, simultaneously. The two
species, asparagine and aspartic acid, give rise to different
racemization kinetics; an initial rapid rate resulting from
aspartic acid racemization followed by a slow rate owing to
the asparagine racemization.[26]
To explain this unusual kinetic behavior of the racemiza-
tion reaction at 208C, we extended our two-component model
discussed above for the nonracemizing system, by combining
the racemization reaction with majority-rules behavior. We
assume that racemization and the dynamic equilibrium
between free monomers and supramolecular polymers take
place simultaneously. In addition, we assume that the
racemization takes place only on the free monomers and
that the dynamic exchange between monomers and the
supramolecular polymers is much faster than the racemiza-
tion. The racemization kinetics are computed starting from
a state with total concentrations [(S)-1]tot and [(R)-1]tot, and
corresponding free monomer concentrations [(S)-1] and
[(R)-1]; these concentrations come from Figure 2b. The free
monomers undergo racemization during a time interval Dt
following first-order kinetics with reaction constant k. The
resulting net change in (S)-1 concentration is defined as
D[(S)-1] = kDt([(R)-1]ꢁ[(S)-1]). Similarly, the net change in
(R)-1 monomers is given by D[(R)-1] = kDt([(S)-1]ꢁ[(R)-1]).
The total concentrations of (S)-1 and (R)-1 (i.e. monomers
within and outside of the supramolecular polymers) change
by D[(S)-1] and D[(R)-1], respectively. From the new total
concentrations, [(S)-1]tot and [(R)-1]tot, after the time interval
Dt, the new free monomer concentrations [(S)-1] and [(R)-1]
can be computed again using the theoretical model for the
nonracemizing system (Figure 2b). In other words, the
racemization during the time Dt leads to a change of the
total concentrations, [(S)-1]tot and [(R)-1]tot, which means
a change in the enantiomeric excess. Hence the system moves
along the x-axis of Figure 2b from a high ee value to an
ee value of zero.
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The time-dependent change of the ee value, which arises
from the racemization, is obtained by repeating this Dt step
using a sufficiently small value for Dt. The racemization
process goes to an equilibrium state where the free monomer
concentrations [(S)-1] and
far more than it would for a first-order rate process, as can be
seen in the logarithmic plot in Figure 2d (graph on right). This
result indicates that the racemization reaction is indeed
limited to the free monomers in solution. The applied model
provides us with detailed information on the composition of
the supramolecular polymer at different ee values and
explains the unusual racemization kinetics.
[(R)-1] are equal. This point corresponds to ee = 0 in Fig-
ure 2b. The only new parameter in this racemization process
is the constant k, which can be taken as the monomer
racemization rate constant when there are no supramolecular
polymers in the medium. By fitting the predicted racemiza-
tion curve to the experimentally determined curve, we can
find a suitable value for k (see Supporting Information for
details). Figure 2d (black line) displays the predicted race-
mization curve, which is in excellent agreement with the
experimental data (red dots). The fast rate in the first phase of
racemization can be rationalized by the large difference
between free (S)-1 and (R)-1 monomer concentrations,
because the racemizing system begins with a high enantio-
meric excess of (S)-1. However, in the second phase, when
considerable (R)-1 has been produced, and therefore at j ee j<
eecr, where the free monomer concentrations of both enan-
tiomers are almost equal (Figure 2b), the process slows down
The theoretical model, with and without racemization,
discussed above provides us with design rules to reach
a nonracemic situation under thermodynamic control during
the racemization of Phg-BTA. We investigated the conse-
quence of adding a chiral additive, a “sergeant”, which forms
P-type supramolecular polymers, similar to those formed by
(S)-1, but is chemically stable to base. The concentrations of
the free monomers in Figure 3a and the concentrations of the
monomers participating in the aggregates in the righthand
graph of Figure 3a were calculated using the same theory and
thermodynamic parameters (see Supporting Information for
details) that had been applied for results in Figure 2b but with
the addition of 8 mol% of the sergeant shown by the black
line in Figure 3a. As depicted in Figure 3a, the free monomer
concentrations in solution change in a nonsymmetrical
Figure 3. a) The computed concentration of free monomers; (S)-1 (blue), (R)-1 (red), and (R)-2 (black) in solution as a function of ee value at
208C; ctot (Phg-BTA)=1.2 mm, DH8mm(between (R)-1 and (S)-1)=ꢁ1.7 kJmolꢁ1, DH8e =ꢁ72.4 kJmolꢁ1, DH8nuc =ꢁ12.2 kJmolꢁ1
,
DS8e =ꢁ0.1477 kJmolꢁ1 Kꢁ1, and 8 mol% sergeant. The same thermodynamic parameters were used for the sergeant. Graph on right:
concentration of monomers residing in the P and M type supramolecular polymers as a function of ee value. b) Molecular representations of the
sergeants (methyl-substituted BTAs (S)-2 and (R)-2). c) The change in ee value over time for mixtures of (S)-1 or (R)-1 with added DBU (1 equiv)
and (S)-2 and (R)-2 as sergeant (8 mol%) at 208C; ctot (Phg-BTA)=1.2 mm in MCH. Triangles, initial ee=ꢁ12%, sergeant: (R)-2; stars, initial
ee=ꢁ4%, sergeant: (R)-2; squares, initial ee=0.2%, sergeant: (S)-2; circles, initial ee=22%, sergeant: (S)-2. d) The computed concentration of
free monomers; (S)-1 (blue), (R)-1 (red), and (R)-2 (black) in solution as a function of ee at 208C; ctot (Phg-BTA)=1.2 mm, DH8mm(between
(R)-1 and (S)-1)=ꢁ5.0 kJmolꢁ1, DH8e =ꢁ72.4 kJmolꢁ1, DH8nuc =ꢁ12.2 kJmolꢁ1, DS8e =ꢁ0.15 kJmolꢁ1 Kꢁ1, and 8 mol% sergeant. The same
thermodynamic parameters were used for the sergeant. Graph on right: concentration of monomers residing in the P and M type supramolecular
polymers ([MP]) as a function of ee value.
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manner as a function of the total ee value because of the
presence of the sergeant. In contrast to the results in
Figure 2b, the concentrations of free (S)-1 (blue line) and
(R)-1 (red line) become equal at a nonzero ee value. As the
sergeant preferably forms P-type aggregates with monomer
(S)-1, the concentration of free (S)-1 monomers decreases
more strongly than that of (R)-1, and interestingly, this
nonzero ee value seems to be approximately equal to eecr from
the two-component system.
When adding a racemization reaction to this three-
component system, racemization between (S)-1 and (R)-1
will consume free (R)-1 monomers to form (S)-1 monomers as
long as the free (R)-1 monomer concentration is higher than
the (S)-1 monomer concentration. As a result of this, the total
ee value increases, including all free enantiomers in solution
and the ones participating in the aggregates. Because the
sergeant favors the P helix formed by the (S)-1 monomer, the
helices formed have the (S)-1 enantiomer in the majority. The
(R)-1 monomers existing in this P helix adjust to the major
helical sense. In the equilibrium state reached in this process,
the free (S)-1 and (R)-1 monomer concentrations are equal.
The overall ee value is determined by the ee value of these
free monomers in combination with the ee value within the
aggregates, which favors (S)-1. The result is a 32% ee value
favoring the (S)-1 enantiomer.
which are important for the reliability of dating methods
based on racemization.[26] We also rationalize how a final
ee value different from zero can be obtained under racemiz-
ing and thermodynamically controlled conditions by adding
a sergeant as chiral auxiliary. This final ee value depends on
the mismatch penalty of the aggregating system. In the
experimental work herein, we achieved the transformation of
a racemic Phg-BTA mixture into a mixture where one of the
enantiomers is present in excess by making use of a chiral
sergeant. The results presented show the strength of combin-
ing theoretical models with experiments. This combination
allows us to understand in detail the supramolecular poly-
merization behavior of a multi-component system and
provides design rules to acheive a nonracemic mixture
under thermodynamic equilibrium in cooperative supra-
molecular systems.
Received: March 2, 2012
Published online: May 16, 2012
Keywords: deracemization · enantiomeric excess ·
.
nonlinear effects · self-assembly · supramolecular chemistry
[1] K. Mislow, Introduction to stereochemistry, Benjamin, New York,
1965, pp. 69.
[2] E. L. Eliel, S. H. Wilen, Stereochemistry of organic compounds,
Wiley, New Jersey, 1994, pp. 426.
We validated our theoretical predictions with experiments
and prepared mixtures of (S)-1 and (R)-1 in MCH (c =
1.2 mm) with varying ee values. We added a small amount
(8 mol%) of nonracemizing (R)-methyl-substituted BTA
((R)-2) as sergeant to these solutions (Figure 3b). The
racemization reaction at room temperature was initiated by
adding DBU (1 equiv) to each solution. Samples were
collected and the total ee values were measured by chiral
HPLC. As shown in Figure 3c, racemization in the presence
of (R)-2 leads to the formation of (S)-Phg-BTA ((S)-1) in
excess and results in an increase in ee value up to 32%
independent of the initial total ee value.
Similarly, application of (S)-methyl-substituted BTA, (S)-
2, as the sergeant resulted in the formation of (R)-Phg-BTA
((R)-1) in excess and the ee value changed to ꢁ32% (Fig-
ure 3c). These experimental results are in excellent agree-
ment with the predicted maximum ee value that can be
obtained by the system. Finally, we investigated the param-
eters that influence the final ee value of a racemizing
supramolecular polymer in the presence of base and sergeant.
Calculations revealed that the position of the eecr is strongly
dependent on the DH8mm between (R)-1 and (S)-1. As shown
in Figure 3d, our model predicts that a racemizing supra-
molecular system with a DH8mm decreased from the value of
[3] K. Faber, Chem. Eur. J. 2001, 7, 5004.
[4] D. B. Amabilino, R. M. Kellogg, Isr. J. Chem. 2011, 51, 1034.
[5] O. Pꢁmies, J. E. Backvall, Chem. Rev. 2003, 103, 3247.
[6] H. Pellissier, Adv. Synth. Catal. 2011, 353, 659.
[7] K. M. Wiggins, C. W. Bielawski, Angew. Chem. 2012, 124, 1672;
Angew. Chem. Int. Ed. 2012, 51, 1640.
[8] W. H. Pirkle, D. S. Reno, J. Am. Chem. Soc. 1987, 109, 7189.
[9] H. Kaku, S. Takaoka, T. Tsunoda, Tetrahedron 2002, 58, 3401.
[10] C. Viedma, Phys. Rev. Lett. 2005, 94, 065504.
[11] W. L. Noorduin, T. Izumi, A. Millemaggi, M. Leeman, H.
Meekes, W. J. P. v. Enckevort, R. M. Kellogg, B. Kaptein, E.
Vlieg, D. G. Blackmond, J. Am. Chem. Soc. 2008, 130, 1158.
[12] W. L. Noorduin, H. Meekes, A. A. C. Bode, W. J. P. van Enck-
evort, B. Kaptein, R. M. Kellogg, E. Vlieg, Cryst. Growth Des.
2008, 8, 1675.
[13] W. L. Noorduin, A. A. C. Bode, M. van der Meijden, H. Meekes,
A. F. v. Etteger, W. J. P. van Enckevort, P. C. M. Christianen, B.
Kaptein, R. M. Kellogg, T. Rasing, E. Vlieg, Nat. Chem. 2009, 1,
729.
[14] J. P. van Enckevort, H. Meekes, B. Kaptein, R. M. Kellogg, J. C.
Tully, J. M. McBride, E. Vlieg, Angew. Chem. 2010, 122, 8613;
Angew. Chem. Int. Ed. 2010, 49, 8435.
[15] A. R. A. Palmans, E. W. Meijer, Angew. Chem. 2007, 119, 9106;
Angew. Chem. Int. Ed. 2007, 46, 8948.
[16] L. Brunsveld, A. P. H. J. Schennning, M. A. C. Broeren, H. M.
Janssen, J. A. J. M. Vekemans, E. W. Meijer, Chem. Lett. 2000,
292.
[17] J. van Gestel, A. R. A. Palmans, B. Titulaer, J. A. J. M. Veke-
mans, E. W. Meijer, J. Am. Chem. Soc. 2005, 127, 5490.
[18] M. M. J. Smulders, P. J. M. Stals, T. Mes, T. F. E. Paffen,
A. P. H. J. Schenning, A. R. A. Palmans, E. W. Meijer, J. Am.
Chem. Soc. 2010, 132, 620.
[19] J. van Gestel, Macromolecules 2004, 37, 3894.
[20] A. J. Markvoort, H. M. M. ten Eikelder, P. A. J. Hilbers, T. F. A.
de Greef, E. W. Meijer, Nat. Commun. 2011, 2, 509.
the current experiment (ꢁ1.7 kJmolꢁ1
;
Figure 3c) to
ꢁ5.0 kJmolꢁ1, reaches an ee value of 74% in the presence
of the sergeant (Figure 3d). Furthermore, the application of
more sergeant (> 8 mol%) and higher Phg-BTA concentra-
tion did not influence the final ee value obtained by the
system (Figure S20).
In conclusion, we studied racemization in a system form-
ing helical supramolecular polymers. The unusual features of
this system can be understood by a theoretical model. One of
the features leads to non-first-order racemization kinetics,
6430 www.angewandte.org
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Angew. Chem. Int. Ed. 2012, 51, 6426 –6431

Angewandte
Chemie
[21] H. M. M. ten Eikelder, A. J. Markvoort, T. F. A. de Greef,
P. A. J. Hilbers, J. Phys. Chem. B 2012, DOI: 10.1021/jp300622m.
[22] M. Tsukamoto, K. Gopalaiah, H. B. Kagan, J. Phys. Chem. B
2008, 112, 15361.
[23] D. Guillaneux, S. H. Zhao, O. Samuel, D. Rainford, H. B. Kagan,
J. Am. Chem. Soc. 1994, 116, 9430.
[24] M. M. J. Smulders, A. P. H. J. Schenning, E. W. Meijer, J. Am.
Chem. Soc. 2008, 130, 606.
[25] P. J. M. Stals, M. M. J. Smulders, R. M. Rapun, A. R. A. Palmans,
E. W. Meijer, Chem. Eur. J. 2009, 15, 2071.
[26] J. Robins, M. Jones, E. Matisoo-Smith, Amino Acid Racemiza-
tion Dating in New Zealand: An Overview and Bibliography,
Aukland University, Aukland, 2001.
Angew. Chem. Int. Ed. 2012, 51, 6426 –6431
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
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