A metal-ion-driven supramolecular chirality pendulum

Article abstract of DOI:10.1002/anie.201004460

Tick tock: The arms of a chirality pendulum can be completely and reversibly moved forward and backward like the pendulum of a clock by coordination and removal of a metal center (see picture). Each motion leads to a complete inversion of the configuratio

Full text of DOI:10.1002/anie.201004460

Communications
DOI: 10.1002/anie.201004460
Molecular Machines
A Metal-Ion-Driven Supramolecular Chirality Pendulum**
Gebhard Haberhauer*
Dedicated to Professor Gꢀnter Helmchen on the occasion of his 70th birthday
The control of molecular states and the mechanical motion of
single molecules by external stimuli is a rapidly expanding
field that is the subject of extensive research.[1,2] A central
aspect of this topic is the control of chirality in order to result
in, for example, unidirectionally controllable rotary motions.
Unidirectionality is one of the most important basic require-
ments for the construction of synthetic molecular machines
whose functionality is based on the
synchronized directed rotary motion of the
machine parts, in analogy to their macro-
scopic models.[3–6]
reversible inversion with high-amplitude motion has not been
reported to date.[10]
We aimed to construct a supramolecular chirality pendu-
lum that can be switched completely and reversibly with high-
amplitude motion between two configurations. Such a system
is presented in Scheme 1. The chiral peptidic clamp[11] in 1
results in the clamp-bound pyridine rings being fixed in a
A particular challenge is the construc-
tion of a chirality pendulum that, like a
mechanically driven pendulum, can be
completely and reversibly transferred from
one configuration to the other with high-
amplitude motion. The problem of con-
structing such a chirality pendulum lies in
the nature of chirality, as enantiomers are
energetically equal in an achiral environ-
ment. Thus it is not possible to shift the
equilibrium toward one state by using
achiral reagents. Therefore the creation of
diastereomers is often applied as a trick for
controlling a chiral state, as one or more
additionally inserted chirality elements lead
to the stabilization of the configuration of
the desired chirality element. A higher
stabilization results in a larger proportion
Scheme 1. Principle of a metal-ion-driven supramolecular chirality pendulum: The diastereo-
mer (P)-1 is energetically stabilized with respect to (M)-1 and can be reversibly converted
into the pseudoenantiomer [(M)-1*M2]4+ by addition of metal ions (M2+).
of the system present in the desired config-
uration. However, the crux of the problem
is that if a certain configuration is highly
stabilized, it is difficult to find a condition
that allows a reversible change of config-
uration, which requires the opposite configuration to also be
stabilized. An inversion of configuration for the systems
described to date, for example, biphenyls,[7] foldamers,[8] and
atranes,[9] could therefore only be obtained by a nontrivial
change, for example, solvent exchange. A complete and
cycle, and thus these units adopt an unambiguous orientation
with respect to each other. As 2,2’-biypridine units show an
N-C-C-N dihedral angle of 1808 in the noncomplexed state, in
order to avoid the repulsion between the lone pairs of
electrons on the nitrogen atoms and to allow a maximum
conjugation over both heteroaromatic rings, the two arms
(red rectangles) on the flexible pyridine rings of the bipyr-
idine ligands have a definite relative spatial configuration
(here the P configuration). A stronger discrimination by the
chiral clamp results in a larger proportion of the P configura-
tion in 1. We did not wish to stabilize the M configuration of 1
during switching because this stabilization would lead to the
above-mentioned difficulties; instead a rotation of the
flexible pyridine rings of the bipyridine ligands should lead
to the change of configuration. This design means that there
should be no change of the overall orientation of the
[*] Prof. Dr. G. Haberhauer
Institut fꢀr Organische Chemie, Fakultꢁt fꢀr Chemie
Universitꢁt Duisburg-Essen
Universitꢁtsstrasse 7, 45117 Essen (Germany)
E-mail: gebhard.haberhauer@uni-due.de
[**] This work was generously supported by the Deutsche Forschungs-
gemeinschaft (DFG). The author thanks Dr. Andreea Schuster and
Dipl.-Chem. Silvia Ernst for helpful support.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201004460.
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bipyridine ligands, as during the transition from (P)-1 to
(M)-1; only the distal parts of the bipyridine ligands should be
rotated by complexation of the 2,2’-bipyridine ligands with
M2+ ions (e.g., Zn2+ or Cu2+), such as during the transition
indeed provides the required discrimination, the energies of
the M and P configurations of 7, which is the basic scaffold of
all chirality pendulums, and the energies of 1a,b were
calculated.[15,16] The H–H distances in 7 and 1a were
determined by 2D NOESY experiments, and CD measure-
ments of 1a–c were carried out and compared with the
calculated spectra of 1a,b.
The structures of (M)-7, (P)-7, (M)-1a,b, and (P)-1a,b
were determined by geometry optimization using B3LYP and
the 6-31G* basis set (Figure 1). The obtained energy differ-
ence between the P and M isomers amounts to 21.7 kJmolꢀ1
for 7, 32.6 kJmolꢀ1 for 1a, and 28.3 kJmolꢀ1 for 1b. Thus, in
all cases, there is an unambiguous preference of the P confi-
guration. On the basis of the Boltzmann distribution, the
chirality pendulums 1 should almost completely (> 99.99%)
adopt the P configuration.
from (P)-1 to [(M)-1*M2]4+ [12]
Nevertheless, the result is the
.
same: in both cases, the arms on the bipyridine ligands are M-
configured. As the complexation of 2,2’-bipyridine ligands by
M2+ ions is a process that goes to completion very rapidly,[13]
a
complete chirality inversion with high-amplitude motion can
occur. Removal of the M2+ ions by addition of a very strong
complexing agent, such as 1,4,8,11-tetraazacyclotetradecane
(cyclam) makes the system reversible.[13]
The synthesis of the chirality pendulums 1 is shown in
Scheme 2. The tetrabromide 5, which contains two ethano-
bridged pyridine units, can be obtained in a few steps from the
commercially available pyridine 2. The secondary nitrogen
atoms of the imidazole units in the chiral clamp 6[11] can be
alkylated with the tetrabromide 5 by using Cs2CO3 as a base.
A double Stille coupling with the tin compound 8 leads to the
chirality pendulum 1a, which has two bromine atoms as arms.
These arms can be elongated by the substitution of the
bromine atoms by methoxyphenylacetylene in a Sonogashira
reaction (1b) or by a zinc tetraarylporphyrin in a Suzuki
reaction (1c).
The first essential requirement for a chirality pendulum is
a distinct energetic discrimination of the P isomer with
respect to the M isomer, so that only the former exists in
solution. To verify whether the effect of the peptidic clamp
Figure 1. Molecular structures of (M)-1b, (P)-1b, and [(M)-1b*(ZnF2)2]
calculated by B3LYP/6-31G*. All hydrogen atoms were omitted for
clarity.
Scheme 2. Synthesis of the chirality pendulums (P)-1. Reaction conditions: a) N-iodosuccinimide, MeOH; b) N-bromosuccinimide, CCl4, 56% (2
steps); c) [CoCl(PPh3)3], toluene, 56%; d) LiAlH4, CH2Cl2; e) HBr/AcOH 90% (2 steps); f) Cs2CO3, CH3CN, reflux, 40%; g) [Pd(PPh3)4], toluene,
35%, h) RH, [PdCl2(PPh3)2], CuI, Et3N, DMF, 55% (for (P)-1b); [Pd(PPh3)4], R’B(C6H12O2),[14] K2CO3, H2O, toluene, 45% (for (P)-1c).
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A further proof for the exclusive existence of 7 and 1 in
1
the P configuration can be found in the H NMR spectra,
which contain only one single set of signals and the protons of
the ethano bridge between the bipyridine ligands show a
typical AA’BB’ set of signals, which indicates a fixed
conformation of this bridge. Moreover, from the H–H
distances in 7 and 1a (determined by 2D NOESY experi-
ments) the three-dimensional structure of 7 and 1 can be
concluded. The spatial structure, which was obtained on
the basis of the distances between the hydrogen atoms,
contains spatially fixed pyridine units that are unambiguously
P-configured.
An unambiguous assignment of the preferred configura-
tion of the arms on the bipyridine ligands should also be
possible on the basis of the CD spectra of 1. The CD spectra of
1a–c were measured in highly dilute CH2Cl2 solution
(Figures 2 and 3). For a better assignment and interpretation,
Figure 3. CD spectra of (P)-1c (blue) and with 6.0 equiv Zn(OTf)2 (!
[(M)-1c*Zn2]4+ , red; c=1.0ꢂ10ꢀ6 m in CH2Cl2).
Cotton effect for (P)-1a; for (M)-1a the Cotton effect
is negative. The calculated spectra of 1a show negative
Cotton effects at approximately 240 nm for (P)-1a as well as
for (M)-1a. These different effects are caused by the peptidic
clamp, which has the same absolute configuration in both
systems. The chirality pendulum 1b also shows similar
behavior (Figure 2). In this case, the absorption band of the
bipyridine ligands is bathochromically shifted to 324 nm
because of the conjugation with the methoxyphenyl moieties
across the triple bond, and shows a positive Cotton effect
(+ 31). This result is consistent with a P configuration of the
phenylacetylene units, as, according to the calculations, the
spectrum of the P isomer exhibits a positive Cotton effect,
whereas the spectrum of the M isomer shows a negative band.
The interpretation of the CD spectrum of 1c is even easier
than the interpretation of the CD spectra of 1a,b, for which
calculations were needed to assign the CD bands. In this case,
the arms on the bipyridine ligands are zinc porphyrin systems,
which exhibit an intense absorption at approximately 420 nm
(the Soret band), for which the rules of exciton chirality can
be applied:[17] strongly absorbing chromophores result in a
very intensive CD pair, and the relative orientation of the
chromophores can be determined by the algebraic sign of the
pair (defined as the algebraic sign of the component with the
higher wavelength). A positive band at a higher wavelength
corresponds to a P configuration. This feature is exactly what
can be observed in the CD spectrum of 1c. Accordingly, we
could show that all chirality pendulums exist exclusively in the
P configuration.
Figure 2. a) CD spectra of (P)-1b (blue) and with 6.0 equiv Zn(OTf)2
(![(M)-1b*Zn2]4+, red; c=1.0ꢂ10ꢀ5 m in CH2Cl2). b) CD spectra of
(P)-1b (blue), (M)-1b (green), and [(M)-1b*(ZnF2)2] (red) calculated
using TD-DFT-PBE1PBE/6-31G* in CH2Cl2.
The second essential requirement for use as a chirality
pendulum is the complexation of the bipyridine ligands with
M2+ ions, which should lead to a 1808 rotation of the flexible
pyridine units (high-amplitude motion) and thus to an
inversion of the configuration of their arms. Zn2+ and Cu2+
ions, both of which bind strongly to bipyridine ligands, were
used in the complexation experiments. In order to prevent the
formation of metal complexes with more than one bipyridine
ligand per metal, the complexation experiments were carried
out at high dilutions and with an excess of metal ions. The
complexation was studied by analyzing the changes in the UV
and CD spectra, which showed similar behavior for both
metal salts. Additionally, the structure of the complex formed
by coordination of (P)-1b with two fragments of ZnF2 was
determined by using B3LYP/6-31G*, and the CD spectrum of
the CD spectra of (M)-1a,b and (P)-1a,b in CH2Cl2 were
simulated with time-dependent density functional theory
(TD-DFT) with the PBE1PBE functional, and by employing
the 6-31G* basis set.[15] As the intensities of the calculated
curves are always higher, they were normalized to the
experimentally determined intensities.
Comparison of the measured with the calculated CD
spectra shows that both 1a and 1b adopt the P configuration
in solution, as can be most clearly observed in the absorption
band of the bipyridine ligands. In the case of 1a, this band
occurs at 297 nm with a positive Cotton effect (+ 42).
Calculations show that this band only exhibits a positive
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As expected, the calculation shows that the complexation
of the bipyridine ligands of (P)-1b by the ZnF2 fragments
leads to an inversion of the configuration of the arms on the
bipyridine ligands and that the complex [(M)-1b*(ZnF2)2]
adopts the M configuration (Figure 1). The complexation and
the concomitant inversion of configuration can also be
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after complexation, as the band for the absorption of the
bipyridine ligands is bathochromically shifted to 353 nm upon
complexation (Figure 2). There is also a simultaneous tran-
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the change of the configuration of the bipyridine arms. Both
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spectrum of [(M)-1b*(ZnF2)2] (Figure 2). The inversion of
chirality in the pendulum 1c, which can be observed by
monitoring the porphyrin Soret band, is particularly impres-
sive; the inversion of configuration leads to a algebraic sign
change of both bands, as predicted by the rules of exciton
chirality.
Swinging of the pendulum in one direction (P!M) can
thus be unambiguously proved. Swinging of the pendulum in
the other direction (M!P), that is, the backward motion,
occurs chemically by addition of cyclam, which forms stronger
complexes with the Zn2+ and Cu2+ ions than the bipyridine
ligands of 1. After the addition of cyclam, the CD spectra of 1
again show the original curve shape. This forward and
backward motion can be repeated several times.
In conclusion, we have shown that it is possible to
construct a supramolecular chirality pendulum. Like the
pendulum of a clock, the arms of the chirality pendulum are
able to swing from one configuration to the other. This
process is reversible, can be repeated several times, is
complete compared to other reported chirality pendulums,
and proceeds with a high change of amplitude. The two
concomitant 1808 rotary motions are therefore suitable for
the construction of more complex molecular machines.
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[15] All calculations were performed with the Gaussian 03 program
package: Gaussian03, Revision C.02, M. J. Frisch et al., Gaus-
sian, Inc., Wallingford CT, 2004.
Received: July 21, 2010
Revised: August 16, 2010
[16] The descriptors M and P used for compound 7 refer to the
configuration of the bridge over the chiral clamp 6. The
descriptors M and P for the chirality pendulums 1 describe the
relative orientation of the arms on the bipyridine ligands.
[17] a) N. Berova, L. Di Bari, G. Pescitelli, Chem. Soc. Rev. 2007, 36,
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Published online: October 21, 2010
Keywords: chirality · circular dichroism · molecular machines ·
.
molecular switches · stereocontrol
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