A torsional strain mechanism to tune pitch in supramolecular helices

Article abstract of DOI:10.1002/anie.200701328

(Figure Presented) On the turn: Torsional strain has been used to control the pitch of helical nanostructures in the range of tens to hundreds of nanometers. In this method, sterically induced torsional strain on the primary helices forces the secondary h

Full text of DOI:10.1002/anie.200701328

Angewandte
Chemie
DOI: 10.1002/anie.200701328
Helical structures
A Torsional Strain Mechanism To Tune Pitch in Supramolecular
Helices**
Liang-shi Li, Hongzhou Jiang, Benjamin W. Messmore, Steve R. Bull, and Samuel I. Stupp*
Inspired by biology, contemporary chemistry is challenged
with the synthesis of architecturally defined functional
structures that are much larger than ordinary molecules.[1]
One emerging strategy is the use of noncovalent interactions
in polymolecular assemblies to craft the shapes, dimensions,
and functions of nanostructures. The scientific goal is to gain
access to unknown static and dynamic functions with supra-
molecular systems which could be designed with the same
ease that small molecules are now synthesized. Supramolec-
ular pores,[2] tubes,[3] cylinders,[4] helices,[5] and mushroomlike
noncentrosymmetric clusters[6] have been among the targets
of recent work in this area. We report here a torsional strain
mechanism to tune the pitch of micrometer-long helical
assemblies in the range of tens to hundreds of nanometers.
Helices in biology, such as double-helical DNA, protein
coiled coils, and twisted b sheets,[7] have inspired an extensive
amount of work on synthetic helical nanostructures.[5] Arti-
ficial structures containing peptide b sheets have been of
particular interest[8,9] since they only require short amino acid
sequences to form and also because of their relevance in
diseases linked to amyloid fibrils. During our recent work on
the functionalization of cylindrical nanofibers formed by
tripeptide amphiphiles in organic solvents (such as cyclohexyl
chloride),[9,10] we found that simple modification of the
compounds led to nanostructures with dramatically different
morphologies.
Compounds 1 and 2 were synthesized with an acetate and
a dimethyl acetate end group, respectively, and we used
atomic force microscopy (AFM) to examine the morphology
of the supramolecular aggregates they form. At a concen-
tration of 1% (by weight) both compounds dissolve in
cyclohexyl chloride at about 808C and form translucent self-
supporting gels upon cooling to room temperature. AFM
studies of the diluted gels dried on silicon substrates revealed
straight cylindrical fibers for compound 1 (Figure 1a). In
contrast, AFM images of the aggregates formed by molecules
of compound 2 show helices with a regular pitch (Figure 1b)
of 22(ꢀ2) nm (Figure 1c), and the orientation of the height
contour clearly indicates these helices have a left-handed
sense.
The significant change in the morphology of the assembly
when the acetate end group in 1 was replaced by a dimethyl
acetate substituent in 2 suggested that a bulkier substituent at
the terminus of the alkyl segment causes twisting of the
initially cylindrical assemblies. To gain a mechanistic view of
this process, we considered first the driving force for
aggregation in these systems. In a low polarity solvent, the
amphiphilic molecules studied here assemble as a result of
solvophobic interactions as well as the formation of an
intermolecular b sheet between the peptide segments.[9] The
charged tetraalkylammonium head groups are buried inside
the nanofibers as a result of their low affinity for the organic
solvent, and the less polar tails are present on the surfaces of
the nanofibers. Infrared absorbance spectroscopy reveals the
formation of parallel b sheets[11] in these aggregates. To
establish the twisted nature of the b sheets[7] in these systems,
we synthesized a diacetylene-containing tripeptide amphi-
phile compound without any bulky substituent in the alkyl
segment and subsequently polymerized the diacetylene
moieties to introduce chromophores into the aggregates.
Circular dichroism spectroscopy on the polymerized aggre-
gates confirmed the helical nature of the b sheets in the
cylindrical nanostructures, which do not reveal any helicity
under AFM.[11] This finding is consistent with the twisted
nature (with left-sense handedness) of the b sheets of almost
all natural proteins.[7]
[*] Dr. L.-S. Li, B. W. Messmore, S. R. Bull, Prof. Dr. S. I. Stupp
Department of Chemistry
Northwestern University
Evanston, IL 60208 (USA)
Fax: (+1)847-491-3010
E-mail: s-stupp@northwesten.edu
Prof. Dr. S. I. Stupp
Feinberg School of Medicine
Northwestern University
Evanston, IL 60208 (USA)
H. Jiang, Prof. Dr. S. I. Stupp
Department of Materials Science and Engineering
Northwestern University
Evanston, IL 60208 (USA)
Dr. L.-S. Li
Permanent address:
Department of Chemistry
Indiana University
Bloomington, IN 47405 (USA)
[**] This work was supported by the US Department of Energy and by
the National Science Foundation.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Angew. Chem. Int. Ed. 2007, 46, 5873 –5876
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5873

Communications
Figure 2. a) Schematic representation of a twisted helical telephone
cord: when a left-handed cord (primary helix) is overwound, its axis
(red) relaxes into a secondary helix (superhelix), and the superhelix is
also left-handed (the green line represents the axis of the superhelix).
The pitch of the superhelix is always larger than that of the primary
helix, and can be varied by changing the magnitude of the torsional
strain applied. A larger torsional strain leads to a smaller pitch and
vice versa. The superhelix has handedness opposite to the primary
helix if the primary helix is unwound (not shown). b) Schematic
representation of an aggregate of tripeptide amphiphile molecules
shaped as a cylindrical nanofiber. One of the internal twisted b sheets
of the aggregate is highlighted in green, and defines a left-handed
primary helix. c) Schematic representation of a superhelix formed by
the supramolecular aggregate as a result of sterically driven internal
strain. One of the b sheets in the superhelix is highlighted in green,
with its axis now making a secondary helix with a much larger pitch.
with superhelices made by overwinding left-handed primary
helices (Figure 2a).[12] The primary helical structures cannot
be resolved with AFM, presumably because of the presence
of multiple b sheets inside the fibers and the flexible alkyl tails
on the surface.
To provide support for the torsional strain mechanism in
the formation of the superhelices, we synthesized three series
of additional compounds 3–11 (Table 1) with end groups of
widely different bulkiness. Compounds 3–11 all formed self-
supporting gels in cyclohexyl chloride. AFM measurements
indicate the formation of helices with the pitch values listed in
Table 1; the estimated van der Waals volume[13] of the end
groups are also given. Straight cylindrical fibers are described
as assemblies having infinite pitch, and as expected the helices
are all left-handed when l-amino acids are used in the
synthesis. Within each of the series (1–3, 4–8, and 9–11), the
pitch of the helices decreases as the van der Waals volume of
the end groups increases. This trend is qualitatively consistent
with the van der Waals picture of liquids and solids,[14] in
which the steric effects produced by the short-range repulsive
forces primarily determine the arrangement of the molecules.
Interestingly, there appears to be a lower limit in the pitch
values for the first two series and the value is the same
(ca. 22 nm) in both series, despite the structural differences in
their end groups. This common limiting value may result from
the requirement to maintain the hydrogen bonds in the
b sheets and to change it further may require variation in the
peptide sequence.
Figure 1. AFM images of the aggregates formed by compounds: a) 1
and b) 2 in cyclohexyl chloride. c) The height profile along the line
connecting the reverse triangles in (b), with the corresponding
positions labeled. Statistical analysis show that these helices have a
pitch of 22(ꢀ2) nm. Scale bars: 100 nm.
The twisted b sheets in cylindrical assemblies indicate the
helical ones formed by compound 2 are actually superhelices
(Figure 2a). The b sheets in these aggregates define the
primary helices (Figure 2b), and the presence of the bulky
end groups could be generating torsional strains that drive the
formation of the superhelix (Figure 2c). Torsional strain
caused by steric repulsion between the bulky substituents may
overwind the b sheets. We propose that the axis of the
b sheets forms a superhelix to accommodate the bulky groups
on the periphery of the b sheets without disrupting the
hydrogen-bonded network (Figure 2c). The observed left-
sense in the assemblies formed by compound 2 is consistent
The pitch of the helices appears to also depend on the
shape and packing of the end groups within the assemblies.
This effect can account for the apparent discrepancy when
comparing compounds across the series listed in Table 1. For
5874
www.angewandte.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2007, 46, 5873 –5876

Angewandte
Chemie
Table 1: Chemical structure of 1–12[a], pitch of the supramolecular helices
they form[b], and estimated van der Waals volumes[c] of their R substituents.
Compound[a]
R
Pitch [nm][b] van der
Waals volu-
me [Š3][c]
Figure 3. a) AFM image of the aggregates formed by 10 and b) height
1
2
1
58.1
profile along the line connecting the reverse triangles in (a). The pitch
of the helices is 90(ꢀ10) nm from statistical analysis. Scale bar:
200 nm.
22(ꢀ2)
92.7
planarity in 6 and 7 can lead to greater strain and thus a
smaller pitch.
3
4
22(ꢀ2)
110.0
It will be some time before we can quantitatively predict
the pitch of the helical molecular assemblies, since the
collective forces involved are complex and difficult to
model in atomistic detail. However, our work clearly shows
that steric forces on the twisted b sheets play an important
role in the tunability of the pitch in the supramolecular
assemblies. We describe this effect here as a torsional strain
mechanism to tune the pitch of a superhelix, analogous to the
observed macroscopic relaxation of primary helices strained
by an applied torque.[12]
The class of compounds studied here share common
characteristics with many others that form helical aggregates,
such as chirality and the ability to form intermolecular
hydrogen bonds or p stacks,[16] and thus we speculate that the
superhelix mechanism described here may be quite general.
Previously, the formation of helical aggregates by chiral
molecules was explained by macroscopic continuum elastic
theories.[17] However, a mechanism bridging molecular chir-
ality and helical morphology over larger length scales has not
been available.[16] We believe the superhelix formation
described here offers a mechanism to fill this gap.
1
113.4
130.7
148.0
5
6
160(ꢀ30)
40(ꢀ3)
7
8
22(ꢀ2)
22(ꢀ2)
165.3
182.6
Potential applications for nanostructures with tunable
pitch include systems to control stereoselective chemistry[18]
and nonlinear optics.[19] In addition, they may also be used for
dynamic processes such as sensing or actuation, provided the
end groups can be modified in situ to impart greater steric
forces through chemical changes. As a proof of principle, we
exposed a suspension of nanofibers made of 12 (Table 1) in
cyclohexyl chloride to UV radiation with a wavelength of
360 nm,[11] and used AFM to study the actuation of the helices
as a result of the trans-to-cis isomerization of the azobenzene
moiety (Figure 4). We observed (Figure 4a and b) that the
light-induced molecular isomerization leads to a reduction in
the pitch of the supramolecular helices. As the cis isomer is
less planar than the trans isomer,[20] the isomerization should
result in an increase of the sterically induced torque, thus
leading to a reduction in the superhelical pitch. The decrease
in the pitch caused by illumination with UV light appears to
vary from nanostructure to nanostructure, thus suggesting an
inhomogeneous level of isomerization in each supramolecular
assembly. Interestingly, however, each nanostructure appears
to have a uniform pitch, which in turn is an indication that the
torque-induced actuation is the result of a relaxation process
throughout the entire assembly. Many opportunities may thus
9
1
104.4
218.2
10
90(ꢀ10)
11
12
60(ꢀ10)
74(ꢀ6)
235.5
292.3
[a] All compounds were synthesized using l-amino acids. [b] The pitch values
are averages obtained from AFM height images of tens of nanostructur-
es.[c] van der Waals volumes are calculated for compounds with the formula
R-H by using the empirical equations in Ref. [13].
example, we expect that the phenyl groups in compound 4
would tend to stack, thereby reducing the torsional strain in
the assembly. Similarly, the nearly disclike shape of benzo-
phenone[15] in 10 would explain the large pitch in the
supramolecular aggregate (Figure 3), while deviation from
Angew. Chem. Int. Ed. 2007, 46, 5873 –5876
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5875

Communications
Saeki, S. Seki, S. Tagawa, M.
Taniguchi, T. Kawai, T.
Aida, Science 2006, 314,
1761.
[4] J. D. Hartgerink, E. Beniash,
Science 2001, 294, 1684.
[5] A. E.
Rowan,
R. J. M.
Nolte, Angew. Chem. 1998,
110, 65; Angew. Chem. Int.
Ed. 1998, 37, 63.
[6] S. I. Stupp, V. LeBonheur,
K. Walker, L. S. Li, K. E.
Huggins, M. Keser, A.
Amstutz, Science 1997, 276,
384.
[7] C. Chothia, J. Mol. Biol.
1973, 75, 295.
[8] J. J. L. M.
J. J. J. M.
Cornelissen,
Donners,
W. S.
R.
Gras-
de Gelder,
winckel, G. A. Metselaar,
A. E. Rowan, N. A. J. M.
Sommerdijk, R. J. M. Nolte,
Science 2001, 293, 676.
Figure 4. AFM height images of the fibers: a) before and b) after exposure to UV light,[11] as well as the
height profiles (c and d) along the straight lines connecting reverse triangles in (a) and (b), respectively. The
helices before illumination are made of the trans isomer, and have a uniform pitch of 78(ꢀ6) nm from
statistical analysis. After exposure to UV light the helix pitch is reduced as the light induces formation of the
nonplanar cis isomer.[20] The pitch value varies from nanostructure to nanostructure, and ranges from 40 nm
to 70 nm. As an example, (b) shows one nanostructure with a pitch of 56(ꢀ)4 nm. Scale bars: 100 nm.
[9] N. Yamada, K. Ariga, M.
Naito, K. Matsubara, E.
Koyama, J. Am. Chem. Soc.
1998, 120, 12192.
[10] L.-S. Li, S. I. Stupp, Angew.
Chem. 2005, 117, 1867;
Angew. Chem. Int. Ed.
2005, 44, 1833.
[11] See the Supporting Information.
emerge in the future for artificial dynamic systems since the
torque prescribing the pitch can be varied by tuning the
interaction between the building blocks within the aggregates.
[12] W. R. Bauer, F. H. C. Crick, J. H. White, Sci. Am. 1980, 243, 118.
[13] Y. H. Zhao, M. H. Abraham, A. M. Zissimos, J. Org. Chem.
2003, 68, 7368.
[14] D. Chandler, J. D. Weeks, H. C. Andersen, Science 1983, 220,
787.
[15] E. B. Fleischer, N. Sung, S. Hawkinson, J. Phys. Chem. 1968, 72,
4311.
Received: March 26, 2007
Published online: July 2, 2007
[16] A. Brizard, R. Oda, I. Huc, Top. Curr. Chem. 2005, 256, 167.
[17] a) J. V. Selinger, M. S. Spector, J. M. Schnur, J. Phys. Chem. B
2001, 105, 7157; b) W. Helfrich, Langmuir 1991, 7, 567.
[18] a) I. Sato, K. Kadowaki, H. Urabe, J. H. Jung, Y. Ono, S. Shinkai,
K. Soai, Tetrahedron Lett. 2003, 44, 721; b) E. M. Wilson-
Kubalek, R. E. Brown, H. Celia, R. A. Milligan, Proc. Natl.
Acad. Sci. USA 1998, 95, 8040.
[19] M. Kauranen, T. Verbiest, C. Boutton, M. N. Teerenstra, K. C.
Clays, A. J. Schouten, R. J. M. Nolte, A. Persoons, Science 1995,
270, 966.
Keywords: helical structures · nanostructures · self-assembly ·
superhelices · torsional strain
.
[1] a) J.-M. Lehn, Proc. Natl. Acad. Sci. USA 2002, 99, 4763;
b) G. M. Whitesides, J. P. Mathias, C. T. Seto, Science 1991, 254,
1312.
[2] V. Percec, A. E. Dulcey, V. S. K. Balagurusamy, Y. Miura, J.
Smidrkal, M. Peterca, S. Nummelin, U. Edlund, S. D. Hudson,
P. A. Heiney, H. Duan, S. N. Magonov, S. A. Vinogradov, Nature
2004, 430, 764.
[20] a) C. J. Brown, Acta Crystallogr. 1966, 21, 146; b) A. Mostad, C.
Romming, Acta Chem. Scand. 1971, 25, 3561.
[3] a) T. Shimizu, M. Masuda, H. Minamikawa, Chem. Rev. 2005,
105, 1401; b) Y. Yamamoto, T. Fukushima, Y. Suna, N. Ishii, A.
5876
www.angewandte.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2007, 46, 5873 –5876