A helical molecule that exhibits two lengths in response to an applied potential

Article abstract of DOI:10.1002/anie.200502240

(Figure Presented) Outstanding in the electric field: Bundles of helical peptides undergo stochastic switching in response to the applied bias polarity as observed by STM. This behavior results from a conformational change between the α-helical (left) and

Full text of DOI:10.1002/anie.200502240

Communications
Molecular Switches
(Aib-Ala)4-OCH3 forms an a helix in the crystalline state.[17]
However, the critical chain length is expected to be longer (10
or 12 residues) for the present case, in which the peptides
immobilized on gold are examined in air or under ultrahigh
vacuum (UHV) because less-polar media tends to favor the
formation of 310 helices in peptides, whereas media of higher
polarity favors the a-helical conformation, as discussed
previously.[16]
In an earlier study, we succeeded in single-molecule
observations of upright helical peptides incorporated into an
alkanethiolate self-assembled monolayer (SAM) by STM.[18]
Notably, these helical peptides display a large dipole moment
parallel to the helical axis from the C terminus to the
N terminus. Therefore, such peptides should be responsive
to an applied electric field. Figure 1a illustrates our exper-
imental design with a helical peptide in which the molecular
length is modulated with the applied bias. The helical
dodecapeptide is immobilized to the gold surface by the
N terminus to expose the negatively charged C terminus at
the top. The peptide can be contracted to the a helix by
placing the STM tip of negative potential on the peptide
C terminus. Alternatively, the peptide favors the 310-helical
conformation by the extension force of the STM tip bearing a
DOI: 10.1002/anie.200502240
A Helical Molecule That Exhibits Two Lengths in
Response to an Applied Potential**
Kazuya Kitagawa, Tomoyuki Morita, and
Shunsaku Kimura*
Molecular devices are expected to play an important role in
advanced electronics in the form of molecular diodes,[1]
molecular transistors,[2] and molecular switches.[3] However,
the electron-transfer mechanism of organic molecules on
metal surfaces—the most fundamental aspect of molecular
devices—still awaits elucidation.[4–6] In an effort to shed light
on this issue, we applied helical peptides as mediators for
long-range electron transfer,[7] a scaffold for chromophores to
accelerate electron transfer,[8] and a viable system for
molecular photodiodes.[9]
Stochastic on–off switching phenomena of molecular
conductance in organic molecules have been observed in
numerous cases through careful observation by scanning
tunneling microscopy (STM).[10–13] These phenomena are
considered to be caused by fluctuations in the hybridization
of the sulfur atom that accompanies the change in molecular
orientation. Our focus is on the use of this mechanism in a
molecular memory device, because one bit may be recognized
by a change in molecular length. For this purpose, however,
the molecule should be able to exhibit two distinct lengths in
response to outer stimuli. Herein, we propose helical peptides
as an appropriate system for the controlled switching of
molecular length on a bulk substrate.
Peptides that contain a-aminoisobutyric acid (Aib) have
the unique ability to adopt two different helical structures: an
a-helical conformation with a short overall length (1.5 Š for
each amino acid residue) and a longer 310-helical conforma-
tion (2.0 Š for each amino acid residue).[14,15] Whereas Boc-
(Ala-Aib)4-OCH3 in crystalline form has been reported to
adopt a 310-helical structure, crystals of Boc-(Ala-Aib)8-OCH3
favor an a-helical structure (Boc = tert-butoxycarbonyl).[16]
This suggests that an intermediate-length dodecapeptide
could have dual a-helical and 310-helical character. The
critical chain length which determines the favored helix
type may be an octapeptide, because para-bromobenzoyl-
[*] K. Kitagawa, Dr. T. Morita, Prof. S. Kimura
Department of Material Chemistry
Graduate School of Engineering, Kyoto University
Kyoto-Daigaku-Katsura, Nishikyo-ku, 615-8510 Kyoto (Japan)
Fax: (+81)75-383-2401
E-mail: shun@scl.kyoto-u.ac.jp
[**] This work is partly supported by a Grant-in-Aid for Scientific
Research B (15350068) from the Ministry of Education, Culture,
Sports, Science, and Technology, Japan. K.K. acknowledges the
Research Fellowships of the Japan Society for the Promotion of
Science for Young Scientists.
Figure 1. a) Conformational change of a dodecapeptide immobilized
onto a gold surface by the N terminus. a Helices and 310 helices are
stabilized by applying a positive (left) and negative (right) bias, respec-
tively. b) Structures of the two dodecapeptides used for the work
reported herein.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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positive potential. Indeed, we observed conductance switch-
ing for the first time in which the apparent molecular lengths
are altered as a function of the polarity of the applied bias
through the use of the two helical dodecapeptides (Fig-
ure 1b). For the experiments reported herein, benzyl ester
was used instead of tert-butyl ester as the protecting group for
the C terminus of the SL12B peptide for synthetic purposes.
However, as the size of benzyl ester of SL12B is similar to that
of a Boc group in the BL12S peptide, the different terminat-
ing groups are not expected to affect the length of the
peptides on the substrate.
Conformational energies of the peptide Ac-(Leu-Aib)n-
OCH3 (n = 4, 6, 8) in a-helical and 310-helical conformations
are calculated semiempirically. The heats of formation
(kcalmolÀ1) are indicated in the parentheses as follows: Ac-
(Leu-Aib)4-OCH3 a helix (À491.759), 310 helix (À492.390);
Ac-(Leu-Aib)6-OCH3
a helix
(À699.056),
310 helix
(À697.146); Ac-(Leu-Aib)8-OCH3 a helix (À907.733),
310 helix (À902.486). The dodecapeptide with the intermedi-
ate length exhibits a small energy difference between the a-
helical and 310-helical conformations, which suggests that
there is facile exchange between the two helical types.
Characterizations of BL12S in solution and in SAMs on
gold were carried out similarly to those of the previous report
on SL12B.[18] Circular dichroism (CD) studies of BL12SAc in
2,2,2-trifluoroethanol and reflection–absorption spectroscopy
(RAS) of the BL12S SAM revealed its a-helical conforma-
tion. From the RAS spectrum, the tilt angle of the helical axis
from the surface normal was calculated to be 458 (Supporting
Information).[7,9,19,20]
We previously observed single molecules or bundles of
SL12B incorporated into dodecanethiolate (C12) SAMs as
bright spots by STM under UHV.[18] BL12S in a C12 SAM is
also observed as bright spots (Figure 2a). Notably, time-
resolved STM images of the BL12S molecules clearly show
switching. Each circle shown in Figure 2a represents a fixed
observation point for the peptide helices. Peptides are
observed as bright spots with apparent length differences of
5 Š from the surrounding dodecanethiolate SAM surface
(ON state). However, these protrusions stochastically disap-
peared (OFF state) and reappeared (ON state) over a time
span of three to four hours.
The effect of the density of the surrounding alkanethiolate
matrix on switching was examined.[10,13] Dodecanethiolate
molecules were found to desorb from the gold surface if
SAMs were left under UHV ( ꢀ 10À8 Pa) for a long period
even at room temperature which resulted in a rearrangement
of the SAM surface structure.[21] Figure 2b shows a series of
STM images of the SL12B/C12 SAM after leaving the sample
under UHV for a long period. The striped pattern of the
matrix monolayer is clearly observable, indicating that the C12
molecules lie down on the surface owing to low surface
coverage. Under these conditions, the molecular motion of
the peptides is allowed more freedom than that of tightly
packed peptides in freshly prepared SAMs. The switching
behaviors shown in Figure 2b, however, occur at a frequency
similar to those shown in Figure 2a; these stochastic switching
data are summarized in Table 1. The average number of
switching events is nearly the same for the loosely packed
Figure 2. a) STM images of BL12S incorporated into the dodecanethio-
late SAM. Images were obtained at a sample bias of 1.4 V and a set-
point current of 2.5 pA. b) STM images of SL12B incorporated into the
dodecanethiolate SAM after leaving the sample under UHV for a long
period (several days). Images were obtained at a sample bias of
À1.3 V and set-point current of 5.0 pA.
Table 1: Summary of stochastic conductance switching events.
Peptide
Parameter
SL12B
BL12S
Alkanethiol density
Number of samples
Observation time [min]
Total number of
tight
9
305
loose
6
306
tight
6
207
loose
9
211
switching events[a]
Average number of
switching events
36
27
19
14
[minÀ1 (500”500 nmÀ2)]
0.50
0.85
0.55
0.47
[a] The total number of switching events was counted by all changes
from ON to OFFand vice versa observed in the STM images between the
two successive scans. Each scan required an average of ꢀ6 min. With an
observation time of 305 min, ꢀ50 images were recorded.
SAM as it is for the tightly packed SAM. The surrounding C12
molecules do not influence the switching behavior, which
suggests that the apparent length change is not a result of the
change of the molecular orientation as has been reported for
oligo(phenylene ethynylene) groups in alkanethiolate
SAMs.[10,13]
The variation of the apparent molecular length of BL12S
is plotted as a function of time (Figure 3a). The dodecapep-
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Communications
ing, then SL12B, which has an orientation opposite to that of
BL12S and which was immobilized to the gold surface by the
N terminus, should also show switching behavior, but with the
opposite response to the applied bias polarity. Figure 4b
shows the bias dependence of the STM images of SL12B.
Indeed, SL12B helices were observed as bright spots at the
negative sample bias, but nearly all peptides apparently
disappeared from the STM image at the positive bias. Taken
together, the dodecapeptides take on a physically elongated
state upon application of an electric field in accordance with
the direction of the dipole moment. The peptide adopts
physically shortened state if the applied electric field is
opposite in direction to the dipole moment. It is speculated
that under a parallel electric field, the peptides are most
stable in a 310-helical conformation (elongated), and under an
opposing electric field direction, the peptides are most stable
in an a-helical conformation (shortened; Figure 1a).
Figure 3. a) Time-lapse STM images (first image, upper left; final
image, lower right) of BL12S peptide molecules incorporated into the
dodecanethiolate SAM; conditions are the same as those reported in
Figure 2. b) Measured molecular length (l) for each image in part a).
The dependence of helical peptide conductivity on the
applied bias polarity was further investigated by scanning
tunneling spectroscopy (STS) at 77 K. Current–voltage (I–V)
curves of the C12 molecules and the peptide helices in the
SAMs are shown in Figure 5. The I–V curve of the matrix C12
tide shows two apparent molecular lengths, and the switching
occurs stochastically in transition between these two states.
As the dodecapeptide is allowed to take both a-helical and
310-helical conformations, the two states may be explained by
an a helix representing the ON state, and a 310 helix
corresponding to the OFF state. This interpretation is
supported strongly by the length difference of 5 Š between
the two states (Figure 3b), which is in agreement with the
molecular-length difference between an a helix and
10 helix.
Because both helix types display a large dipole moment
a
3
along the helical axis,[22] it is expected that the polarity of the
applied voltage between the STM tip and the gold substrate
influences the STM image of the peptides.[23,24] BL12S was
observed by STM under application of the positive sample
bias as described above. When the sample bias was inverted
from positive to negative, the bright spots of BL12S disap-
peared within a few scans, but they reappeared with a return
to the positive bias (Figure 4a).
Figure 5. Current–voltage (I–V) curves of dodecanethiolate (thin
dotted line), BL12S (thick dotted line), and SL12B (thick solid line)
acquired at the temperature of liquid nitrogen (77 K). The lines repre-
sent the average of 20–30 individual responses.
If the interaction of the peptide dipole moment with the
applied electric field is the origin of this conductance switch-
molecules shows a featureless monotonic increase in the
range from À2 to +2 V.[25,26] On the contrary, asymmetric I–V
responses are observed for the helices. In the case of BL12S,
the current increased more dramatically at the positive
sample bias than at the negative bias. On the other hand,
the current through SL12B increased more strongly at the
negative bias than that at the positive bias. Both results
indicate that the current through the helix is enhanced by
applying the bias voltage such that the direction of the electric
field coincides with the helical dipole moment. Therefore, the
I–V characteristics of the helices also support the interpreta-
tion that the helix dipole moment interacts with the external
electric field to convert between a-helical and 310-helical
conformations.
Figure 4. Sequential STM images of a) BL12S (set-point current of 4.5 pA) and
b) SL12B (set-point current of 5.0 pA) incorporated into the dodecanethiolate
SAM with alternation of the polarity of the applied sample bias voltage.
In conclusion, we observed conductance switching of
peptide helix bundles by STM. The conductance and the
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[23] C. G. Worley, R. W. Linton, E. T. Samulski, Langmuir 1995, 11,
apparent molecular length were observed to undergo sto-
chastic changes with time. The conductance of the helix
alternated between two states by changing the polarity of
applied bias. This novel behavior can be explained by the
conformational change between an a helix and a 310 helix.
The helical structure is influenced by the applied electric field
as a result of the interaction with the large dipole moment of
the helix. This means that the apparent molecular length can
be regulated by an external stimulus. The precise control of
the switching of the helices is now under investigation.
3805.
[24] Y. Miura, S. Kimura, S. Kobayashi, M. Iwamoto, Y. Imanishi, J.
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[26] D. J. Wold, C. D. Frisbie, J. Am. Chem. Soc. 2001, 123, 5549.
Received: June 25, 2005
Keywords: electron transfer · helical structures · monolayers ·
.
peptides · scanning probe microscopy
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