A molecular leverage for helicity control and helix inversion

Article abstract of DOI:10.1021/ja205570z

The helical tetranuclear complex [LZn₃La(OAc)₃] having two benzocrown moieties was designed and synthesized as a novel molecular leverage for helicity control and helix inversion. Short alkanediammonium guests H₃N⁺(CH₂)_nNH₃ ⁺ (n = 4, 6, 8) preferentially stabilized the P-helical isomer of [LZn₃La(OAc)₃], while the longer guest H₃N ⁺(CH₂)₁₂NH₃⁺ caused a helix inversion to give the M-helical isomer as the major isomer. The differences in the molecular lengths were efficiently translated into helical handedness via the novel molecular leverage mechanism using the gauche/anti conversion of the trans-1,2-disubstituted ethylenediamine unit.

Full text of DOI:10.1021/ja205570z

COMMUNICATION
pubs.acs.org/JACS
A Molecular Leverage for Helicity Control and Helix Inversion
Shigehisa Akine,* Sayaka Hotate, and Tatsuya Nabeshima*
Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8571, Japan
S Supporting Information
b
Scheme 1. (a) Helicity Control of a Tetranuclear Complex
ABSTRACT: The helical tetranuclear complex [LZn3La-
(OAc)3] having two benzocrown moieties was designed and
synthesized as a novel molecular leverage for helicity control
and helix inversion. Short alkanediammonium guests H3N+-
by a Chiral Auxiliary; (b) Design of a Helical Metal Complex
for Strategic Helix Inversion by a Molecular Leverage
Mechanism
+
(CH2)nNH3 (n = 4, 6, 8) preferentially stabilized the
P-helical isomer of [LZn3La(OAc)3], while the longer guest
H3N+(CH2)12NH3+ caused a helix inversion to give the M-
helical isomer as the major isomer. The differences in the
molecular lengths were efficiently translated into helical
handedness via the novel molecular leverage mechanism
using the gauche/anti conversion of the trans-1,2-disubsti-
tuted ethylenediamine unit.
elical structures are frequently seen in functional biomole-
H
cules such as DNA and proteins. Their helical handedness
principally depends on the chiral structures of their constituents,
such as deoxyribose and amino acids. However, inversion of their
helical handedness sometimes takes place.1,2 Developing such a
helix inversion system based on artificial molecular frameworks
has been a fascinating research objective that has attracted many
chemists. For example, there have been reports of artificial mole-
cules or polymers whose handedness can be changed by external
stimulation such as a change in temperature3 or solvent,4 redox
reaction,5 light irradiation,6 addition of chemical species,7 dis-
solution of crystals,8 or various combinations of these stimulating
events.9
In this study, we aimed to create a novel helix inversion system
that is remotely driven using a molecular leverage mechanism
(Figure 1). To date, various kinds of molecular machines10 such
as molecular shuttles and motors have been developed, and
recently, much attention has focused on molecular systems that
can convert linear motion into rotary motion.11 However, there
have been no reports of a mechanism that can convert linear
motion into helix inversion. To realize such a conversion, a rational
and well-programmed mechanism should be incorporated into an
invertible helix such as a labile helical metal complex,12 which is
flexible enough to undergo helix inversion upon capture of the
external stimulus. We now report the first molecular machinery
mechanism in which molecular length as an input is translated into
helical handedness as an output by means of a novel leverage
mechanism (Figure 1) based on the gauche/anti conversion of the
trans-1,2-disubstituted ethylenediamine unit (Scheme 1).
The helix inversion strategy in this study was inspired by our
previous study13,14 of helicity control of single-helical tetra-
nuclear complexes bearing a chiral auxiliary. In these complexes,
the helicity of the preferred isomer depends on the relatively
small chiral auxiliary, an ethylenediamine moiety, located at the
Received: June 15, 2011
Published: July 29, 2011
Figure 1. Concept of a molecular leverage mechanism for helix
inversion.
r
2011 American Chemical Society
13868
dx.doi.org/10.1021/ja205570z J. Am. Chem. Soc. 2011, 133, 13868–13871
|

Journal of the American Chemical Society
COMMUNICATION
Scheme 2. Synthesis of H6L
Figure 2. CD spectral changes of [LZn3La(OAc)3] upon the addition
of G4 in 1:1 chloroform/methanol at 0.02 mM concentration.
periphery of the molecule (Scheme 1a). Therefore, if we change
the NꢀCꢀCꢀN torsion angle of the ethylenediamine moiety
from +60° to ꢀ60° (or vice versa), we can invert the handedness
of the helical scaffold of the tetranuclear complex moiety.
To realize this idea, we designed a helical metal complex
equipped with a new transducer mechanism based on the (S,S)-
trans-1,2-disubstituted ethylenediamine unit, whose helical hand-
edness can be inverted by taking advantage of the hostꢀguest
interaction between the diammonium guests and 18-crown-6
substituents (Scheme 1b). When the complex recognizes a long
(or short) diammonium guest, the two crown ether substituents
are in the anti (or gauche) position relative to each other. This
geometry corresponds to an NꢀCꢀCꢀN torsion angle of ꢀ60°
(or +60°) in the ethylenediamine moiety, which defines the
preferred handedness of the helical scaffold as M (or P). Using
this molecular leverage mechanism, we can efficiently control
the helical handedness by changing the molecular length of the
diammonium guests.
of the diamine unit as a chiral auxiliary (50% diastereomeric
excess) presumably results from the fact that there is only a small
difference in the two conformations (18-crown-6 moieties in the
anti and gauche positions), which means that the arrangement of
the crown moieties does not perfectly control the helicity.
However, this diastereomeric ratio of the right- and left-
handed isomers was changed by molecular recognition of the
+
alkanediammonium guests H3N+(CH2)nNH3 (TsOꢀ)2 (Gn;
n = 4, 6, 8, 10, 12) at the 18-crown-6 sites. It is well-known that
18-crown-6 derivatives can strongly interact with a primary
alkylammonium cation in the cavity. We expected that a shorter
alkanediammonium guest Gn would shorten the distance
between the two 18-crown-6 moieties while a longer one would
extend it.
When the short guest G4 was added to a solution of
[LZn3La(OAc)3] in 1:1 chloroform/methanol, the Cotton effect
of the [LZn3La(OAc)3] at 352 nm increased (Figure 2). The
intensity increased by up to 61% relative to that of [LZn3La-
(OAc)3] itself when 5 equiv of G4 was present. The binding
constant for the 1:1 hostꢀguest complexation was calculated to
be log Ka = 4.36 (Ka in Mꢀ1). Since the absorption spectra did
not significantly change upon hostꢀguest complexation, this
increase can be ascribed to the change in the P/M diastereomeric
ratio. The major isomer (the P isomer) was preferentially stabi-
lized by the recognition of the diammonium guest G4. In contrast,
The synthesis of the new tris(chelate) ligand H6L bearing two
18-crown-6 moieties is shown in Scheme 2. Chiral diamine 3
bearing two 18-crown-6 moieties was synthesized by enantiose-
lective [3,3]sigmatropy15 using 4-formylbenzo-18-crown-6 (1)16
and chiral diamine 2. The reaction of diamine 3 with aldehyde 417
afforded the H6L ligand. Complexation of the H6L ligand with
zinc(II) acetate (3 equiv) and lanthanum(III) acetate (1 equiv)
afforded the tetranuclear complex [LZn3La(OAc)3] (Figures S1
and S2 in the Supporting Information). The formation of the
tetranuclear species was confirmed by the electrospray ionization
(ESI) mass spectrometry (m/z 1839.7 for [LZn3La(OAc)2]+
and 890.3 for [LZn3La(OAc)]2+). The [LZn3La(OAc)3] com-
plex showed a UVꢀvis spectrum similar to that of the com-
plex without crown moieties, indicating that the zinc(II) and
lanthanum(III) ions are in the peripheral N2O2 and the central
O8 binding sites, respectively. The tetranuclear complex [LZn3-
La(OAc)3] existed as a mixture of two diastereomers; the diaste-
reomeric ratio was determined to be 75:25 in1:1 CDCl3/CD3OD
the addition of a monoammonium cation, C12H25NH3 Clꢀ, did
+
not change the CD spectrum at all. Therefore, the change in the
CD spectrum upon the addition of G4 can be attributed to
binding of the guest in a bridging fashion. The change in the dia-
stereomeric ratio was confirmed by NMR spectroscopy. When
2 equiv of G4 was added, the 75:25 ratio changed to 85:15. The
increase in the diastereomeric excess from 50% to 70% is
responsible for the increase in the CD intensity.
Similar changes were observed in the case of the longer guests
G6 and G8. The CD intensities increased by 50% and 35% when
5 equiv of G6 and G8, respectively, were added (Figure S4). In
contrast, no change was observed upon the addition of G10. It
1
using H NMR spectroscopy. The helical handedness of the
major isomer was determined to be P on the basis of the CD
spectrum in 1:1 chloroform/methanol, which showed a positive
Cotton effect at 352 nm (Figure S3).13b The relatively weak effect
13869
dx.doi.org/10.1021/ja205570z |J. Am. Chem. Soc. 2011, 133, 13868–13871

Journal of the American Chemical Society
COMMUNICATION
Scheme 3. Equilibrium Constants for P/M Isomerization
and Guest Binding of [LZn3La(OAc)3]
isomers as well as the chemical shifts (Figure 4). Upon the
addition of G12, the mole fraction of the P isomer decreased and
that of the M isomer increased. The P/M ratio of 75:25 changed
to 34:66 upon the addition of 2 equiv of G12. This corresponds to
a reversal of the diastereomeric excess from 50% to ꢀ32%. The
equilibrium constants for P/M isomerization and guest binding
(Scheme 3), which were determined by nonlinear least-squares
regression of the NMR data, clearly showed the reversal of the
0
P/M preference (Kiso = 0.37 to Kiso = 2.2) upon guest binding
and a 6-fold higher guest-binding affinity of the M isomer relative
to the P isomer.
Figure 3. CD spectral changes of [LZn3La(OAc)3] upon the addition
of G12 in 1:1 chloroform/methanol at 0.02 mM concentration.
Consequently, binding of G12 to [LZn3La(OAc)3] produces
helical handedness opposite to that for G4 binding. As we
expected, the longer guest G12 extends the distance between
the two 18-crown-6 moieties to make the NꢀCꢀCꢀN torsion
angle negative, which stabilizes the M isomer of the helix. On the
other hand, the shorter guest G4 keeps the distance short,
resulting in a positive NꢀCꢀCꢀN torsion angle and stabiliza-
tion of the P isomer. The difference in the molecular lengths is
efficiently transferred into a change in helical handedness.
This reported helix inversion system is of interest as the first
molecular transducer that changes linear motion (extension
and contraction) into helix inversion (right-handed and left-
handed). The conversion between the anti and gauche forms of
the trans-1,2-disubstituted ethylenediamine unit enables this
strategic helix inversion. The basic concept of this mechanical
helicity inversion could also be applied to the switching of a
variety of chiral functions. The combination of this system with
other mechanical motions such as molecular shuttles and cranks
would lead to well-controlled molecular machinery on the
nanometer scale.
Figure 4. 1H NMR spectral changes of [LZn3La(OAc)3] upon the
addition of the longer guest G12 (400 MHz, 1:1 CDCl3/CD3OD,
1 mM). The P/M ratios were determined by deconvolution of the peak
profiles.
’ ASSOCIATED CONTENT
S
Supporting Information. Synthetic procedure for
b
appeared that the intensity change was smaller as the chain length
increased.
[LZn3La(OAc)3], 1H NMR spectra of H6L and [LZn3La(OAc)3],
and CD spectra of [LZn3La(OAc)3]. This material is available free of
charge via the Internet at http://pubs.acs.org.
However, the longer guest G12 had a drastically different
effect. The addition of G12 to the solution resulted in a decrease
in the Cotton effect at 352 nm followed by inversion (Figure 3).
When 5 equiv of the guest was present, the CD spectrum showed
a significant negative Cotton effect at 362 nm. This strongly
indicated that the binding to G12 caused inversion of the helical
handedness, with the M isomer becoming preferred. The ESI
massspectrum of[LZn3La(OAc)3] in the presence of G12 showed
’ AUTHOR INFORMATION
Corresponding Author
akine@chem.tsukuba.ac.jp; nabesima@chem.tsukuba.ac.jp
peaks at m/z 680.7, 718.0, and 755.4 for [LZn3LaX2 H3N-
3
(CH2)12NH3]3+ (X = OAc, OTs), indicating the formation of
1:1 hostꢀguest complex.
’ ACKNOWLEDGMENT
To study the inversion in more detail, the complexation was
investigated using 1H NMR spectroscopy. The addition of guest
G12 resulted in changes in the mole fractions of the P and M
This work was supported by Grants-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports, Sci-
ence and Technology, Japan.
13870
dx.doi.org/10.1021/ja205570z |J. Am. Chem. Soc. 2011, 133, 13868–13871

Journal of the American Chemical Society
COMMUNICATION
’ REFERENCES
(14) For related salen-containing chiral helices, see: (a) Zhang, F.;
Bai, S.; Yap, G. P. A.; Tarwade, V.; Fox, J. M. J. Am. Chem. Soc. 2005,
127, 10590. (b) Dong, Z.; Karpowicz, R. J., Jr.; Bai, S.; Yap, G. P. A.; Fox,
J. M. J. Am. Chem. Soc. 2006, 128, 14242. (c) Dong, Z.; Yap, G. P. A.; Fox,
J. M. J. Am. Chem. Soc. 2007, 129, 11850.
(15) (a) Kim, H.-J.; Kim, H.; Alhakimi, G.; Jeong, E. J.; Thavarajah,
N.; Studnicki, L.; Koprianiuk, A.; Lough, A. J.; Suh, J.; Chin, J. J. Am.
Chem. Soc. 2005, 127, 16370. (b) Kim, H.; Nguyen, Y.; Yen, C. P.-H.;
Chagal, L.; Lough, A. J.; Kim, B. M.; Chin, J. J. Am. Chem. Soc. 2008,
130, 12184.
(16) D’Souza, F.; Chitta, R.; Gadde, S.; McCarty, A. L.; Karr, P. A.;
Zandler, M. E.; Sandanayaka, A. S. D.; Araki, Y.; Ito, O. J. Phys. Chem. B
2006, 110, 5905.
(17) (a) Akine, S.; Taniguchi, T.; Saiki, T.; Nabeshima, T. J. Am.
Chem. Soc. 2005, 127, 540. (b) Akine, S.; Matsumoto, T.; Sairenji, S.;
Nabeshima, T. Supramol. Chem. 2011, 23, 106.
(1) (a) Herbert, A.; Rich, A. Genetica 1999, 106, 37. (b) Wells, R. D.
Trends Biochem. Sci. 2007, 32, 271. (c) Bacolla, A.; Wells, R. D. Mol.
Carcinog. 2009, 48, 273. (d) Zhao, J.; Bacolla, A.; Wang, G.; Vasquez,
K. M. Cell. Mol. Life Sci. 2010, 67, 43.
(2) (a) Blout, E. R.; Karlson, R. H. J. Am. Chem. Soc. 1958, 80, 1259.
(b) Hashimoto, M.; Aritomi, J. Bull. Chem. Soc. Jpn. 1966, 39, 2707.
(c) Toriumi, H. Macromolecules 1984, 17, 1599. (d) Sasaki, S.; Ogawa,
H.; Kimura, S. Polym. J. 1991, 23, 1325. (e) Inai, Y.; Komori, H.; Ousaka,
N. Chem. Rec. 2007, 7, 191.
(3) (a) Bouman, M. M.; Meijer, E. W. Adv. Mater. 1995, 7, 385. (b)
Maeda, K.; Okamoto, Y. Macromolecules 1999, 32, 974. (c) Fujiki, M. J.
Am. Chem. Soc. 2000, 122, 3336. (d) Peterca, M.; Imam, M. R.; Ahn,
C.-H.; Balagurusamy, V. S. K.; Wilson, D. A.; Rosen, B. M.; Percec, V.
J. Am. Chem. Soc. 2011, 133, 2311.
(4) (a) Okamoto, Y.; Nakano, T.; Ono, E.; Hatada, K. Chem. Lett.
1991, 525. (b) Bidan, G.; Guillerez, S.; Sorokin, V. Adv. Mater. 1996, 8,
157. (c) Nakako, H.; Nomura, R.; Masuda, T. Macromolecules
2001, 34, 1496. (d) Maeda, K.; Morino, K.; Yashima, E. J. Polym.
Sci., Part A: Polym. Chem. 2003, 41, 3625. (e) Miyake, H.; Sugimoto, H.;
Tamiaki, H.; Tsukube, H. Chem. Commun. 2005, 4291. (f) Okoshi, K.;
Sakurai, S.-i.; Ohsawa, S.; Kumaki, J.; Yashima, E. Angew. Chem.,
Int. Ed. 2006, 45, 8173. (g) Sakurai, S.-i.; Okoshi, K.; Kumaki, J.;
Yashima, E. J. Am. Chem. Soc. 2006, 128, 5650. (h) Johnson, R. S.;
Yamazaki, T.; Kovalenko, A.; Fenniri, H. J. Am. Chem. Soc. 2007, 129,
5735.
(5) (a) Zahn, S.; Canary, J. W. Science 2000, 288, 1404. (b) Canary,
J. W.; Zahn, S. Trends Biotechnol. 2001, 19, 251. (c) Barcena, H. S.;
Holmes, A. E.; Zahn, S.; Canary, J. W. Org. Lett. 2003, 5, 709. (d) Zahn,
S.; Das, D.; Canary, J. W. Inorg. Chem. 2006, 45, 6056.
(6) Maxein, G.; Zentel, R. Macromolecules 1995, 28, 8438.
(7) (a) Yano, S.; Nakagoshi, M.; Teratani, A.; Kato, M.; Onaka, T.;
Iida, M.; Tanase, T.; Yamamoto, Y.; Uekusa, H.; Ohashi, Y. Inorg. Chem.
1997, 36, 4187. (b) Yashima, E.; Maeda, Y.; Okamoto, Y. J. Am. Chem.
Soc. 1998, 120, 8895. (c) Miyake, H.; Yoshida, K.; Sugimoto, H.;
Tsukube, H. J. Am. Chem. Soc. 2004, 126, 6524. (d) Miyake, H.; Kamon,
H.; Miyahara, I.; Sugimoto, H.; Tsukube, H. J. Am. Chem. Soc. 2008,
130, 792. (e) Miyake, H.; Hikita, M.; Itazaki, M.; Nakazawa, H.;
Sugimoto, H.; Tsukube, H. Chem.—Eur. J. 2008, 14, 5393. (f) Meudtner,
R. M.; Hecht, S. Angew. Chem., Int. Ed. 2008, 47, 4926. (g) Kim, H.; So,
S. M.; Yen, C. P.-H.; Vinhato, E.; Lough, A. J.; Hong, J.-I.; Kim, H.-J.;
Chin, J. Angew. Chem., Int. Ed. 2008, 47, 8657.
(8) (a) Gregoliꢀnski, J.; Lisowski, J. Angew. Chem., Int. Ed. 2006,
ꢀ
45, 6122. (b) Gregoliꢀnski, J.; Slepokura, K.; Lisowski, J. Inorg. Chem.
2007, 46, 7923. (c) Gregoliꢀnski, J.; Starynowicz, P.; Hua, K. T.; Lunkley,
J. L.; Muller, G.; Lisowski, J. J. Am. Chem. Soc. 2008, 130, 17761.
(9) (a) Zhao, H.; Sanda, F.; Masuda, T. Macromol. Chem. Phys. 2005,
206, 1653. (b) Maeda, K.; Mochizuki, H.; Watanabe, M.; Yashima, E.
J. Am. Chem. Soc. 2006, 128, 7639.
(10) For reviews, see: (a) Balzani, V.; Credi, A.; Raymo, F. M.;
Stoddart, J. F. Angew. Chem., Int. Ed. 2000, 39, 3348. (b) Kay, E. R.;
Leigh, D. A.; Zerbetto, F. Angew. Chem., Int. Ed. 2007, 46, 72.
(c) Champin, B.; Mobian, P.; Sauvage, J.-P. Chem. Soc. Rev. 2007,
36, 358. (d) Kinbara, K.; Aida, T. Chem. Rev. 2005, 105, 1377.
(11) (a) Hiraoka, S.; Shiro, M.; Shionoya, M. J. Am. Chem. Soc. 2004,
126, 1214. (b) Hiraoka, S.; Hirata, K.; Shionoya, M. Angew. Chem., Int.
Ed. 2004, 43, 3814. (c) Kinbara, K.; Muraoka, T.; Aida, T. Org. Biomol.
Chem. 2008, 6, 1871. (d) Okuno, E.; Hiraoka, S.; Shionoya, M. Dalton
Trans. 2010, 39, 4107.
(12) (a) Lehn, J.-M. Supramolecular Chemistry: Concepts and Per-
spectives; VCH: Weinheim, Germany, 1995. (b) Constable, E. C. Tetra-
hedron 1992, 48, 10013. (c) Piguet, C.; Bernardinelli, G.; Hopfgartner,
G. Chem. Rev. 1997, 97, 2005.
(13) (a) Akine, S.; Taniguchi, T.; Matsumoto, T.; Nabeshima, T.
Chem. Commun. 2006, 4961. (b) Akine, S.; Matsumoto, T.; Nabeshima,
T. Chem. Commun. 2008, 4604. (c) Akine, S.; Hotate, S.; Matsumoto, T.;
Nabeshima, T. Chem. Commun. 2011, 47, 2925.
13871
dx.doi.org/10.1021/ja205570z |J. Am. Chem. Soc. 2011, 133, 13868–13871