Chirally twisted oligo(phenyleneethynylene) by cyclization with α-helical peptide

Article abstract of DOI:10.1021/jo9001905

A novel cyclic conjugate of a helical decapeptide and oligo(phenyleneethynylene) (OPE), C-OPE10, was synthesized. The conformation and the optical properties of the cyclic conjugate were studied by circular dichroism (CD), absorption, and emission spectro

Full text of DOI:10.1021/jo9001905

Chirally Twisted Oligo(phenyleneethynylene) by Cyclization with
r-Helical Peptide
Hidenori Nakayama and Shunsaku Kimura*
Graduate School of Engineering, Kyoto UniVersity, Kyoto-Daigaku-Katsura, Nishikyo-ku,
Kyoto 615-8510, Japan
shun@scl.kyoto-u.ac.jp
ReceiVed February 11, 2009
A novel cyclic conjugate of a helical decapeptide and oligo(phenyleneethynylene) (OPE), C-OPE10,
was synthesized. The conformation and the optical properties of the cyclic conjugate were studied by
circular dichroism (CD), absorption, and emission spectroscopies. In the cyclic conjugate, the rotational
motion around the molecular axis of the OPE moiety was hindered to take a chirally twisted conformation,
which is a distorted form from the coplanar conjugated structure, as revealed by observation of an induced
negative Cotton effect of the OPE moiety. Molecular simulation using time dependant-density functional
theory indicated a right-handed twist conformation of the OPE moiety for the negative Cotton effect.
This conjugate therefore provides a new way to obtain a π-conjugated compound having main-chain
chirality. The optical properties of the OPE moiety taking the twist conformation in the cyclic conjugate
are also discussed in depth.
Introduction
when quenching due to molecular stacking is avoided,19-21
which are also useful for application to high-sensitive chemical
sensors.22-30
Poly- and oligo(phenylenethynylene)s (PPE/OPEs) are highly
π-conjugated compounds with rigid linear backbone,1-5 which
are currently attracting great interest in electronic and optical
engineering fields. Because one of the emerging applications
of the π-conjugated compounds is opto-electronics materials,
the fluorescence and the electron transport properties have been
studied extensively both from experimental6-14 and theoreti-
cal15-18 aspects. Further, PPEs/OPEs become highly fluorescent
Allara, D. L. Nano Lett. 2005, 5 (1), 61–65.
(11) Cygan, M. T.; Dunbar, T. D.; Arnold, J. J.; Bumm, L. A.; Shedlock,
N. F.; Burgin, T. P.; Jones, L.; Allara, D. L.; Tour, J. M.; Weiss, P. S. J. Am.
Chem. Soc. 1998, 120 (12), 2721–2732.
(12) Moore, A. M.; Dameron, A. A.; Mantooth, B. A.; Smith, R. K.; Fuchs,
D. J.; Ciszek, J. W.; Maya, F.; Yao, Y.; Tour, J. M.; Weiss, P. S. J. Am. Chem.
Soc. 2006, 128 (6), 1959–1967.
(1) Bunz, U. H. F. Chem. ReV. 2000, 100 (4), 1605–1644.
(2) Tour, J. M. Acc. Chem. Res. 2000, 33 (11), 791–804.
(3) Tour, J. M.; Rawlett, A. M.; Kozaki, M.; Yao, Y.; Jagessar, R. C.; Dirk,
S. M.; Price, D. W.; Reed, M. A.; Zhou, C.-W.; Chen, J.; Wang, W.; Campbell,
I. Chem.sEur. J. 2001, 7 (23), 5118–5134.
(4) Hwang, J.-J.; Tour, J. M. Tetrahedron 2002, 58 (52), 10387–10405.
(5) Price, D. W.; Dirk, S. M.; Maya, F.; Tour, J. M. Tetrahedron 2003, 59
(14), 2497–2518.
(13) Moore, A. M.; Mantooth, B. A.; Donhauser, Z. J.; Yao, Y.; Tour, J. M.;
Weiss, P. S. J. Am. Chem. Soc. 2007, 129 (34), 10352–10353.
(14) Beebe, J. M.; Kim, B.; Frisbie, C. D.; Kushmerick, J. G. ACS Nano
2008, 2 (5), 827–832.
(15) Yin, X.; Li, Y.; Zhang, Y.; Li, P.; Zhao, J. Chem. Phys. Lett. 2006, 422
(1-3), 111–116.
(16) Segal, D.; Nitzan, A.; Davis, W. B.; Wasielewski, M. R.; Ratner, M. A.
J. Phys. Chem. B 2000, 104 (16), 3817–3829.
(6) Dhirani, A.; Lin, P. H.; Guyot-Sionnest, P.; Zehner, R. W.; Sita, L. R.
J. Chem. Phys. 1997, 106 (12), 5249–5253.
(7) Sachs, S. B.; Dudek, S. P.; Hsung, R. P.; Sita, L. R.; Smalley, J. F.;
Newton, M. D.; Feldberg, S. W.; Chidsey, C. E. D. J. Am. Chem. Soc. 1997,
119 (43), 10563–10564.
(17) Kushmerick, J. G.; Holt, D. B.; Yang, J. C.; Naciri, J.; Moore, M. H.;
Shashidhar, R. Phys. ReV. Lett. 2002, 89 (8), 086802-086802.
(18) Seminario, J. M.; Zacarias, A. G.; Tour, J. M. J. Am. Chem. Soc. 1998,
120 (16), 3970–3974.
(19) Halkyard, C. E.; Rampey, M. E.; Kloppenburg, L.; Studer-Martinez,
S. L.; Bunz, U. H. F. Macromolecules 1998, 31 (25), 8655–8659.
(20) Li, H.; Powell, D. R.; Hayashi, R. K.; West, R. Macromolecules 1998,
31 (1), 52–58.
(8) Bumm, L.; Arnold, J.; Cygan, M.; Dunbar, T.; Burgin, T.; Jones, L.;
Allara, D.; Tour, J.; Weiss, P. Science 1996, 271 (5256), 1705–1707.
(9) Zangmeister, C. D.; Robey, S. W.; vanZee, R. D.; Yao, Y.; Tour, J. M.
J. Phys. Chem. B 2004, 108 (41), 16187–16193.
(21) Remmers, M.; Schulze, M.; Wegner, G. Macromol. Rapid Commun.
1996, 17 (4), 239–252.
(10) Selzer, Y.; Cai, L.; Cabassi, M. A.; Yao, Y.; Tour, J. M.; Mayer, T. S.;
3462 J. Org. Chem. 2009, 74, 3462–3468
10.1021/jo9001905 CCC: $40.75 2009 American Chemical Society
Published on Web 04/07/2009

Chirally Twisted Oligo(phenyleneethynylene)
Fundamental spectroscopic properties of PPE/OPEs have been
studied intensively. One of the interesting features in these
compounds is an unusual strong asymmetry between absorbance
and emission spectra.31-35 To interpret this phenomenon several
theoretical models have been proposed. Liu et al.36 have
successfully reproduced absorption spectra of PPE/OPEs with
ab initio calculation using the quadratic coupling model.37,38
Another characteristic feature is appearance of a sharp batho-
chromic band in absorption spectra in poor solvents or solid
state.19,26,39,40 Kim et al. have explained the phenomenon in
terms of the conformation of PPE confined in a Langmuir film.40
They clearly showed that cofacial π-aggregation was the reason
for the sharp band. Masuo et al. encapsulated a PPE rigid chain
within dendrimers and found that no bathochromic band was
observed even in poor solvating environment or in solid state
for the PPE.26
The spectroscopic spectra of PPE/OPEs are strongly depend-
ent on molecular conformation. The rotational barrier of adjacent
phenyl rings around the acetylene linkage is known to be less
than 1 kcal/mol.18,41 The rotational barrier is therefore compara-
tive to kBT in a solution at room temperature, resulting in near-
to-free rotation of the phenyl rings. Since the π-conjugation state
of PPE/OPEs is strongly coupled to the dihedral angle of
adjacent phenyl rings, spectroscopic properties of PPE/OPEs
are tunable by regulating the phenyl ring rotation. Indeed, several
efforts have been made to promote the planar conformation of
PPE/OPEs.42-45 Hu et al. have recently succeeded in inducing
the planar conformation of the OPE using intramolecular
hydrogen bond formation.45 They showed that the maximum
absorption wavelength of the planar OPE was 20-40 nm longer
than nonplanar ones. Reversely, if a PPE/OPE is fixed in a
twisted conformation, its absorption should show a hypsochro-
mic shift as shown by Brizius et al. who have studied on twisted
diphenylacetylenes.46 Yang et al. have also reached to the same
conclusion from the experiment using pentiptycene-modified
OPEs.47
In the present work, we tried to regulate rotation of phenyl
rings by clipping the two points of OPE with a helical peptide
to induce a chirally twisted conformation in the OPE. The key
point of using the helical peptide as a bridge for the two
terminals of the OPE is to induce main-chain chirality with help
of the chiral helicity of the peptide. We synthesized a novel
OPE-peptide cyclic conjugate C-OPE10 as well as a linear
conjugate L-OPE10 as a reference compound (Figure 1). OPE
having two carboxyl groups was bridged by a helical decapep-
tide composed of alternating alanine (Ala) and R-aminoisobu-
tylic acid (Aib). Aib rich oligopeptides are known to take a
310- or an R-helical structure.48 The molecular length of a helical
decamer is estimated to be 1.5-2 nm, which is close to that of
OPE (1.7 nm). The helical peptide should be effective not only
for restriction of the rotational motion in OPE but also for
induction of a chiral twist on it. The conformation of the peptide
decamer and the OPE moiety were studied by circular dichroism
(CD) spectroscopy, and the electronic structures of the OPE
moiety were discussed based on absorption and emission
spectroscopies. For detailed discussion on CD measurements,
ab initio calculations were performed using time dependent
(TD)-density functional theory (DFT).
(22) Zhou, Q.; Swager, T. M. J. Am. Chem. Soc. 1995, 117 (50), 12593–
12602.
(23) Zhou, Q.; Swager, T. M. J. Am. Chem. Soc. 1995, 117 (26), 7017–
7018.
(24) Yang, J. S.; Swager, T. M. J. Am. Chem. Soc. 1998, 120 (46), 11864–
11873.
Results and Discussion
(25) Yang, J. S.; Swager, T. M. J. Am. Chem. Soc. 1998, 120 (21), 5321–
5322.
(26) Masuo, S.; Yoshikawa, H.; Asahi, T.; Masuhara, H.; Sato, T.; Jiang,
D. L.; Aida, T. J. Phys. Chem. B 2003, 107 (11), 2471–2479.
(27) Sato, T.; Jiang, D. L.; Aida, T. J. Am. Chem. Soc. 1999, 121 (45), 10658–
10659.
(28) Ogoshi, T.; Takashima, Y.; Yamaguchi, H.; Harada, A. Chem. Commun.
2006, (35), 3702–3704.
(29) McQuade, D. T.; Pullen, A. E.; Swager, T. M. Chem. ReV. 2000, 100
(7), 2537–2574.
(30) Satrijo, A.; Swager, T. M. J. Am. Chem. Soc. 2007, 129 (51), 16020–
16028.
(31) Cornil, J.; Beljonne, D.; Heller, C. M.; Campbell, I. H.; Laurich, B. K.;
Smith, D. L.; Bradley, D. D. C.; Mullen, K.; Bredas, J. L. Chem. Phys. Lett.
1997, 278 (1-3), 139–145.
(32) Sluch, M. I.; Godt, A.; Bunz, U. H. F.; Berg, M. A. J. Am. Chem. Soc.
2001, 123 (26), 6447–6448.
(33) Karabunarliev, S.; Baumgarten, M.; Bittner, E. R.; Mullen, K. J. Chem.
Phys. 2000, 113 (24), 11372–11381.
(34) Gierschner, J.; Mack, H.-G.; Luer, L.; Oelkrug, D. J. Chem. Phys. 2002,
116 (19), 8596–8609.
(35) Heimel, G.; Daghofer, M.; Gierschner, J.; List, E. J. W.; Grimsdale,
A. C.; Mullen, K.; Beljonne, D.; Bredas, J.-L.; Zojer, E. J. Chem. Phys. 2005,
122 (5), 054501-11.
(36) Liu, L. T.; Yaron, D.; Sluch, M. I.; Berg, M. A. J. Phys. Chem. B 2006,
110 (38), 18844–18852.
Conformation of Peptide. To investigate the conformation
of the peptide moieties of L-OPE10 and C-OPE10, CD spectra
were measured in methanol at room temperature (Figure 2a).
The spectrum of L-OPE10 showed a weak positive Cotton
effect around 220 nm, suggesting that two moieties of the
peptide pentamers in L-OPE10 take a disordered conforma-
tion,49 although some pentamers consisted of Ala and Aib
residues are known to take a 310- or an R-helical structure.50
On the other hand, C-OPE10 showed clearly a double-minimum
pattern (peaks at 208 and 222 nm), which is characteristic of
an R-helical structure.49,51 Otoda et al. have investigated on the
critical length for transition from a 310- to an R-helix of Boc-
(Ala-Aib)n-OMe to be eight residues on the basis of X-ray
analysis of the crystalline structures.48 The present observation
for the peptide decamer in C-OPE10 is in agreement with the
previous finding.
Although the CD spectrum of C-OPE10 showed the clear
pattern of R-helix, the structure was not so stable. The helix
content was determined as 23% and decreased further upon
raising temperature from 10 to 50 °C (Figure 2b). These facts
(37) Keil, T. H. Phys. ReV. 1965, 140 (2A), A601–A601.
(38) Myers, A. B.; Trulson, M. O.; Mathies, R. A. J. Chem. Phys. 1985, 83
(10), 5000–5006.
(39) Fiesel, R.; Halkyard, C. E.; Rampey, M. E.; Kloppenburg, L.; Studer-
Martinez, S. L.; Scherf, U.; Bunz, U. H. F. Macromol. Rapid Commun. 1999,
20 (3), 107–111.
(40) Kim, J.; Swager, T. M. Nature (London) 2001, 411 (6841), 1030–1034.
(41) Okuyama, K.; Hasegawa, T.; Ito, M.; Mikami, N. J. Phys. Chem. 1984,
88 (9), 1711–1716.
(42) Crisp, G. T.; Bubner, T. P. Tetrahedron 1997, 53 (34), 11899–11912.
(43) Crisp, G. T.; Bubner, T. P. Tetrahedron 1997, 53 (34), 11881–11898.
(44) McFarland, S. A.; Finney, N. S. J. Am. Chem. Soc. 2002, 124 (7), 1178–
1179.
(45) Hu, W.; Zhu, N.; Tang, W.; Zhao, D. Org. Lett. 2008, 10 (13), 2669–
2672.
(46) Brizius, G.; Billingsley, K.; Smith, M. D.; Bunz, U. H. F. Org. Lett.
2003, 5 (21), 3951–3954.
(47) Yang, J. S.; Yan, J. L.; Hwang, C. Y.; Chiou, S. Y.; Liau, K. L.;
GavinTsai, H. H.; Lee, G. H.; Peng, S. M. J. Am. Chem. Soc. 2006, 128 (43),
14109–14119.
(48) Otoda, K.; Kitagawa, Y.; Kimura, S.; Imanishi, Y. Biopolymers 1993,
33 (9), 1337–1345.
(49) Chen, Y.-H.; Yang, J. T.; Martinez, H. M. Biochemistry 1972, 11 (22),
4120–4131.
(50) Vijayakumar, E. K. S.; Balaram, P. Tetrahedron 1983, 39 (16), 2725–
2731.
(51) Holzwarth, G.; Doty, P. J. Am. Chem. Soc. 1965, 87 (2), 218–228.
J. Org. Chem. Vol. 74, No. 9, 2009 3463

Nakayama and Kimura
FIGURE 2. Circular dichroism (CD) spectra of (a) C-OPE10 (solid)
and L-OPE10 (dot), and (b) temperature dependence of CD spectra of
C-OPE10 with raising from 10 (blue) to 50 °C (orange; every 10 °C).
of a rigid rod-shaped OPE like a molecular splint. One reason
for failure in stabilization of the helical structure should be
unsuitable geometry for the OPE moiety to bridge the two points
of the peptide with taking R-helical structure. The distance
between the two terminal residues of the R-helical decapeptide
may be longer than the OPE counterpart, because the side chains
of the two terminal residues make a dihedral angle of about
80° around the helix axis and are not straight along the helix
axis. Another reason for instability in the R-helix may be
competition between 310- and R-helical structures. When the
temperature was raised to 50 °C, the peak at 222 nm nearly
disappeared and became a shoulder, which is close to the typical
CD spectrum pattern for 310-helical structure.56
FIGURE 1. Chemical structures and schematic presentations of (a)
C-OPE10 and (b) L-OPE10.
indicate that the R-helical structure is most dominant in the
decamer but has only a little advantage in stabilization against
other structures.52-55 Because the molar ellipticity per residue
of the C-OPE10 (ca. -1 × 104 deg cm-2 dmol-1 residue-1 at
222 nm) was close to that of the free dodecamer of five repeats
of the Ala-Aib alternating sequence,52 the decapeptide moiety
was not stabilized in its helical structure despite the connection
Characterization of the OPE Moiety. Absorption and
emission spectra of C-OPE10 and L-OPE10 in methanol were
measured (Figure 3). The absorption spectra of C-OPE10 and
L-OPE10 showed well-resolved vibrational bands at 373, 340,
and 320 nm, which is typical for OPE with a few functional
(52) Miura, Y.; Kimura, S.; Imanishi, Y.; Umemura, J. Langmuir 1998, 14
(24), 6935–6940.
(53) Morita, T.; Kimura, S.; Kobayashi, S.; Imanishi, Y. J. Am. Chem. Soc.
2000, 122 (12), 2850–2859.
(54) Kitagawa, K.; Morita, T.; Kimura, S. J. Phys. Chem. B 2004, 108 (39),
15090–15095.
(55) Kai, M.; Takeda, K.; Morita, T.; Kimura, S. J. Pept. Sci. 2008, 14 (2),
192–202.
(56) Toniolo, C.; Polese, A.; Formaggio, F.; Crisma, M.; Kamphuis, J. J. Am.
Chem. Soc. 1996, 118 (11), 2744–2745.
3464 J. Org. Chem. Vol. 74, No. 9, 2009

Chirally Twisted Oligo(phenyleneethynylene)
FIGURE 4. CD spectra of C-OPE10 and L-OPE10 in methanol.
FIGURE 3. Normalized absorption and emission spectra of C-OPE10
(solid) and L-OPE10 (dot) in methanol.
C-OPE10 and L-OPE10 were homogeneously dissolved in
methanol. Therefore, the negative induced CD of C-OPE10
should reflect a twist conformation of the OPE moiety upon
bridging by a right-handed helix. As far as we know, this is the
first example to prepare a π-conjugated compound having main-
chain chirality by bridging the twisted OPE terminals with a
chiral helix, which is distinctly different from the previous report
by Fiesel et al. who have also synthesized soluble PPPs having
main-chain chirality.63
The negative Cotton effect of C-OPE10 shows little change
with increasing temperature, which is a sharp contrast to the
peptide moiety. The reason may be due to the flexible linker
between the OPE moiety and the helical peptide to buffer the
influence of the thermal fluctuation of the helical peptide on
the OPE moiety, but the detail remains to be solved.
groups.36,57,58 No sharp band at the longer wavelength was
observed in both absorption spectra under the present conditions
(ca. 15 µM for both C-OPE10 and L-OPE10). The emission
spectra of the both compounds also showed clear vibrational
bands as the absorption spectra. The mirror image symmetry
between absorption and emission spectra was broken similarly
to the other reports on PPE/OPEs32,57 as well as poly(phenyle-
nevinylene)s (PPVs)19,31,34 and poly(p-phenylene)s (PPPs).35
When the two absorption spectra were normalized by the
intensity at 320 nm, C-OPE10 shows nearly identical absorption
and emission spectra with L-OPE10. There are two possible
interpretations for the identical spectra: one is the helix bridge
does not hinder the free rotation of the aromatic groups around
the ethynylene axis, and the other is the fixed conformation of
the OPE moiety by the helix bridge happens to show similar
spectra to the average conformation of the OPE moiety in
L-OPE10, where nearly frictionless rotation is allowed around
the ethynylene axis.18,41 We conclude the latter interpretation
is applied to the present case as following.
To investigate the conformation of the OPE moiety, CD
spectra were recorded in the absorption region of the OPE
(260-360 nm). A negative Cotton effect was observed with
C-OPE10 (Figure 4), whereas no peaks with L-OPE10. CD
spectra of π-conjugate polymers such as PPE,59 PPV,60 and
PPP61,62 have been examined for the purpose of fabrication of
circularly polarized electroluminescence materials. Cotton effects
of those compounds appeared upon formation of chiral ag-
gregation due to the chirality introduced in aliphatic side chains.
This chiral aggregation is, however, not the case for C-OPE10,
because no aggregation band in the absorption spectrum was
observed in the present concentration range (13-16 µM). Both
The conformation of the OPE moiety is further studied by
ab initio calculations on model compounds. To start with,
geometry 1 (Figure 5) was prepared by optimization with the
DFT method on the B3LYP/6-31G(d,p) level. The vibration
analysis revealed that 1 located at a local minimum in the energy
potential. The dihedral angles of the three phenyl rings of 1
were less than 1°. Geometries 2, R15, and L15 (Figure 5) were
prepared by changing the dihedral angles between the phenyl
rings from 1. Geometry 2 is a coplanar conformation, where
two substituents of the OPE moiety were located at the same
side. Geometry R15 has a dihedral angle of 15° between two
adjacent phenyl rings in a right-handed way, whereas L15 in a
left-handed way. Single-point calculation on the four geometries
were performed using TD-DFT method using B3LYP/6-
31G(d,p) basis set. The predicted absorption and CD spectra
are shown in Figure 6. The maximum absorption wavelength
is 364 nm for 1 and 2, and 361 nm for R15 and L15. This
reflects that the π-conjugation is weakened in R15 and L15
because the coplanar geometry of 2 is twisted. The calculated
CD spectra of R15 and L15 show a negative and positive Cotton
effect at the maximum absorbance wavelength, respectively
(Figure 6b). It is thus concluded that the OPE moiety in
C-OPE10 should take the right-handed conformation. However,
(57) Levitus, M.; Schmieder, K.; Ricks, H.; Shimizu, K. D.; Bunz, U. H. F.;
Garcia-Garibay, M. A. J. Am. Chem. Soc. 2001, 123 (18), 4259–4265.
(58) James, P. V.; Sudeep, P. K.; Suresh, C. H.; Thomas, K. G. J. Phys.
Chem. A 2006, 110 (13), 4329–4337.
(59) Fiesel, R.; Halkyard, C. E.; Rampey, M. E.; Kloppenburg, L.; Studer-
Martinez, S. L.; Scherf, U.; Bunz, U. H. F. Macromol. Rapid Commun. 1999,
20 (3), 107–111.
(60) Peeters, E.; Christiaans, M. P. T.; Janssen, R. A. J.; Schoo, H. F. M.;
Dekkers, H. P. J. M.; Meijer, E. W. J. Am. Chem. Soc. 1997, 119 (41), 9909–
9910.
the calculated ellipticity of R15 (-3.3 × 104 deg cm2 dmol-1
)
is five times larger than the measured value (ca. -6 × 103 deg
cm2 dmol-1). CD spectra of 2 were calculated with varying the
dihedral angles from 5 to 90° (Figure 7). The Cotton effect at
(61) Oda, M.; Nothofer, H. G.; Lieser, G.; Scherf, U.; Meskers, S. C. J.;
Neher, D. AdV. Mater. 2000, 12 (5), 362–365.
(62) Fiesel, R.; Scherf, U. Acta Polym. 1998, 49 (8), 445–449.
(63) Fiesel, R.; Huber, J.; Apel, U.; Enkelmann, V.; Hentschke, R.; Scherf,
U.; Cabrera, K. Macromol. Chem. Phys. 1997, 198 (9), 2623–2650.
J. Org. Chem. Vol. 74, No. 9, 2009 3465

Nakayama and Kimura
FIGURE 5. Geometries of the model compounds. A gray ball represents a carbon atom, white represents hydrogen, red represents oxygen, and
blue represents nitrogen.
FIGURE 7. Calculated CD spectra on right-hand twisted geometries
with varying the dihedral angles between two phenyl rings around the
molecular axis.
5°. This estimation, however, is not reliable due to the impre-
cision of the calculated intensity. At the moment, the twisted
angle is considered to be less than 15°.
Conclusions
Novel helical peptide-OPE conjugates C-OPE10 (cyclized)
and L-OPE10 (linear) were prepared. From CD measurements,
the decapeptide moiety in C-OPE10 was revealed to take
R-helical structure, whereas two pentamers in L-OPE10 took
random structure. Observation of the induced negative Cotton
effect of the OPE moiety in C-OPE10 indicated a twisted
conformation of the OPE moiety in C-OPE10 because two
phenyl rings were bridged by the R-helical decapeptide.
Calculations showed a right-handed twist conformation of the
OPE moiety. We provide here a new method to prepare a
π-conjugated compound having main-chain chirality by bridging
the OPE with a chiral helix. Such compounds will be applied
for interesting chiroptical materials. Further modification of OPE
with another helical peptide to load more tension on the OPE
moiety is now under investigation.
FIGURE 6. Computed (a) absorption and (b) CD spectra of geometries
1 (dot), R15 (solid), and L15 (dash). The absorption and CD spectra
of 2 are nearly identical to those of 1. The absorption spectra of R15
and L15 are also identical.
the maximum absorption wavelength increases as the twisting
angle increases from 0 to 60°. If the twist angle is more than
60°, the negative Cotton effect starts decreasing sharply and
finally drops down to zero at 90°, where chirality disappears.
When the measured molar ellipticity is compared with the
computed ones, the twisted angle is estimated to be less than
Experimental Section
Materials. C-OPE10 and L-OPE10 were synthesized according
to Scheme S1 in Supporting Information. The peptides were
3466 J. Org. Chem. Vol. 74, No. 9, 2009

Chirally Twisted Oligo(phenyleneethynylene)
synthesized by the conventional liquid-phase method. The OPEs
were synthesized by the Sonogashira coupling. Tetrahydrofuran
(THF) used as solvent in the Sonogashira coupling was distilled
over calcium hydride and butylated hydroxyl toluene. The other
reagents were used as purchased. All intermediates were identified
by 1H NMR spectroscopy and some of them were further confirmed
by fast atom bombardment (FAB) mass spectrometry. The NMR
peak assignments for compounds 1-8 were confirmed with HH-
COSY. The purity of the products was checked by thin layer
chromatography (TLC). The purity of the final compounds were
further analyzed by HPLC (ODS column, eluant: CH3CN/H2O/
trifluoroacetic acid ) 45/55/0.05 for C-OPE10; CH3CN/H2O )
90/10 for L-OPE10; flow rate: 1 mL/min; monitor at 355 nm).
Synthesis. Boc-(Ala-Aib)2-OPac (2). To Boc-(Ala-Aib)2-OH
(550 mg, 1.29 mmol) in DMF were added phenacylbromide (513
mg, 2.58 mmol) and triethylamine (TEA; 360 µL, 2.58 mmol) at 0
°C. The reaction mixture was stirred at room temperature for 3 h,
followed by concentration under reduced pressure. The residue was
taken up with chloroform and washed with 4% aq NaHCO3 (3×),
brine, 4% aq KHSO4 (2×), and brine. The organic layer was dried
over MgSO4 and concentrated under reduced pressure. The residue
was washed with hexane and diisopropylether, giving 677 mg (1.23
mmol, 95% yield).
(m, 1H, AlaCR), 5.07 (dd, 2H, COOCH2Ph), 5.12 (s, 1H, OrnNHδ),
5.33 (dd, 2H, OCH2COPh), 6.80 (s, 1H, OrnNHCR), 6.93 (d, 1H,
AlaNH), 7.06-7.13 (m, 2H, AibNH), 7.29-7.36 (m, 6H, aromatic
and AibNH), 7.49 (t, 2H, aromatic), 7.62 (m, 1H, aromatic), 7.92
(d, 2H, aromatic).
Ac-Orn(PhI)-(Ala-Aib)2-OPac (5). Compound 4 (630 mg, 0.852
mmol) was treated with HBr/AcOH. The HBr salt was washed with
diethlether. To the peptide in DMF were added 3-iodobenzoic acid
(434 mg, 1.75 mmol), HATU (1.33 g, 3.5 mmol), and DIEA (914
µL, 5.25 mmol) at 0 °C, and the mixture was kept stirring under a
N2 atmosphere at room temperature for 30 h. The mixture was
concentrated under reduced pressure. The residue was taken up with
chloroform and washed with water, 4% aq NaHCO3 (3×), brine,
4% aq KHSO4 (2×), and brine. The organic layer was dried over
MgSO4 and concentrated under reduced pressure. The residue was
further purified with a column chromatography (silica gel, chloroform/
methanol ) 30/1) and washed with diisopropylether, giving 448
mg (0.537 mmol, 61% yield).
1H NMR (400 MHz, CDCl3) δ 1.37-1.60 (m, 20H, AibCꢀ,
AlaCꢀ, OrnCꢀ), 1.81 (m, 2H, OrnCγ), 2.06 (s, 3H, Ac), 3.51 (m,
2H, OrnCδ), 4.07 (m, 1H, AlaCR), 4.35 (m, 1H, AlaCR), 4.44 (m,
1H, OrnCR), 5.30 (dd, 2H, OCH2COPh), 6.78-6.83 (m, 2H,
OrnNHδ, AibNH), 7.07-7.13 (m, 2H, AlaNH, OrnNHR), 7.15-7.21
(m, 2H, AlaNH, aromatic), 7.32 (s, 1H, AibNH), 7.50 (m, 2H,
aromatic), 7.62 (m, 1H, aromatic), 7.85 (d, 1H, aromatic), 7.85-7.96
(m, 3H, aromatic), 8.18 (s, 1H, aromatic). FAB-MS (matrix: NBA)
Calcd for C36H48IN6O9 [(M + H)+], 835.24; found, 835.3.
Boc-(Ala-Aib)2-Orn(Z)-OMe (6). To 1 (1.36 g, 3.16 mmol) and
the HCl salt of Orn(Z)-OMe (1.20 g, 3.79 mmol) in DMF were
added HATU (1.80 g, 4.74 mmol) and DIEA (1.93 mL, 11.1 mmol)
at 0 °C. The reaction mixture was kept stirring under a N2
atmosphere for 22 h. The mixture was concentrated under reduced
pressure. The residue was taken up with ethyl acetate and washed
with water, 4% aq NaHCO3 (3×), brine, 4% aq KHSO4 (2×), and
brine. The organic layer was dried over MgSO4 and concentrat-
ed under reduced pressure. The product was further purified with
a column chromatography (silica gel, chloroform/methanol ) 50/
1), giving 1.36 g (1.96 mmol, 62%).
1H NMR (400 MHz, CDCl3) δ 1.35-1.39 (m, 6H, AlaCꢀ), 1.42
(s, 9H, Boc), 1.57 (s, 3H, AibCꢀ), 1.61 (s, 3H, AibCꢀ), 1.64 (s,
3H, AibCꢀ), 1.70 (s, 3H, AibCꢀ), 3.95 (m, 1H, AlaCR), 4.47 (m,
1H, AlaCR), 4.99 (s, 1H, urethane), 5.33 (s, 2H, OCH2COPh), 6.56
(s, 1H, NHCO), 7.32 (s, 1H, NHCO), 7.33 (s, 1H, NHCO), 7.49
(t, 2H, aromatic), 7.62 (d, 1H, aromatic), 7.92 (d, 2H, aromatic).
FAB-MS (matrix: 3-nitrobenzylalcohol (NBA)) calcd for
C27H41N4O8 [(M + H)+], 549.28; found, 549.4.
Boc-Orn(Z)-(Ala-Aib)2-OPac (3). Compound 2 (676 mg, 1.23
mmol) was treated with 4 N HCl/dioxane. The HCl salt was washed
with diethylether. To the peptide in DMF were added Boc-Orn(Z)
(667 mg, 1.82 mmol), O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetram-
ethyluronium hexafluorophosphate (HATU; 923 mg, 2.43 mmol),
and diisopropylethylamine (DIEA; 739 µL, 4.25 mmol) at 0 °C.
The reaction mixture was stirred under a N2 atmosphere at room
temperature for 30 h. Additional portions of HATU (200 mg, 0.53
mmol) and DIEA (120 µL, 0.70 mmol) were added to the mixture
at 0 °C. The mixture was further stirred for 10 h and concentrated
under reduced pressure. The residue was taken up with ethyl acetate
and washed with water, 4% aq NaHCO3 (3×), brine, 4% aq KHSO4
(2×), and brine. The organic layer was dried over MgSO4 and
concentrated under reduced pressure. The residue was further
purified with column chromatography (silica gel, chloroform/
methanol ) 50/1), giving 830 mg (1.03 mmol, 85% yield).
1H NMR (400 MHz, CDCl3) δ 1.37-1.60 (m, 29H, AibCꢀ,
AlaCꢀ, OrnCꢀ, Boc), 1.75 (m, 2H, OrnCγ), 3.24-3.17 (m, 2H,
OrnCδ), 4.02 (s, 1H, OrnCR), 4.02 (s, 1H, OrnCR), 4.11 (m, 1H,
AlaCR), 4.41 (m, 1H, AlaCR), 5.07 (s, 2H, COOCH2Ph), 5.12 (s,
1H, OrnNHδ), 5.33 (s, 2H, OCH2COPh), 5.42 (s, 1H, OrnNHR),
6.72 (s, 1H, AlaNH), 7.06 (d, 1H, AlaNH), 7.16 (s, 1H, AibNH),
7.29-7.36 (m, 6H, aromatic and AibNH), 7.49 (t, 2H, aromatic),
7.62 (m, 1H, aromatic), 7.92 (d, 2H, aromatic). FAB-MS (matrix:
NBA) Calcd for C40H57N6O11 [(M + H)+], 797.40; found, 797.3.
Ac-Orn(Z)-(Ala-Aib)2-OPac (4). Compound 3 (830 mg, 1.04
mmol) was treated with 4 N HCl/dioxane. The HCl salt was washed
with diethylether. To the peptide were added acetic anhydride (3
mL) and pyridine (9 mL). The reaction mixture was stirred at room
temperature for 30 h, and the solution was poured into water. The
aqueous layer was extracted with chloroform. The organic layer
was washed with brine, dried over MgSO4, and concentrated under
reduced pressure. The residue was purified with column chroma-
tography (silica gel, chloroform/methanol ) 50/1, then 10/1), giving
630 mg (0.85 mmol, 88%).
1H NMR (400 MHz, CDCl3) δ 1.37-1.64 (m, 27H, AibCꢀ, Boc,
AlaCꢀ), 1.76-1.90 (m, 4H, OrnCꢀ, OrnCγ), 3.21 (s, 2H, OrnCδ),
3.68 (s, 3H, OCH3), 3.88 (m, 1H, AlaCR), 4.05 (m, 1H, AlaCR),
4.44 (m, 1H, OrnCR), 5.05 (s, 2H, COOCH2Ph), 5.20 (s, 1H,
AlaNH), 5.67 (s, 1H, OrnNHδ), 6.49 (s, 1H, AibNH), 7.28 (s, 1H,
OrnNHR), 7.31 (s, 5H, aromatic), 7.62 (d, 1H, AlaNH). FAB-MS
(matrix: NBA) Calcd for C33H53N6O10 [(M + H)+], 693.37; found,
693.4.
Boc-(Ala-Aib)2-Orn(PhI)-OMe (7). To 6 (1.3 g, 1.88 mmol)
in methanol was added Pd/C (260 mg). The reaction mixture was
kept stirring under a H2 atmosphere for 24 h. Another portion of
Pd/C (50 mg) was added to the mixture and stirred for another
26 h. The catalyst was filtered off, and the filtrate was concentrated
under reduced pressure. To the peptide in DMF were added
3-iodobenzoic acid (592 mg, 2.39 mmol), HATU (1.51 g, 3.98
mmol), and DIEA (0.832 µL, 4.78 mmol) at 0 °C. The reaction
mixture was kept stirring under a N2 atmosphere for 14 h at room
temperature. Additional portions of HATU (600 mg, 1.6 mmol)
and DIEA (554 µL, 3.2 mmol) were added to the mixture and stirred
for 24 h. The mixture was concentrated under reduced pressure.
The residue was taken up with chloroform and washed with water,
4% aq NaHCO3 (3×), brine, 4% aq KHSO4 (2×), and brine. The
organic layer was dried over MgSO4 and concentrated under
reduced pressure. The residue was further purified by a column
chromatography (silica gel, chloroform/methanol ) 50/1, then 10/
1), giving 451 mg (0.80 mmol, 35%).
1H NMR (400 MHz, CDCl3) δ 1.37-1.68 (m, 27H, AibCꢀ, Boc,
AlaCꢀ), 1.72 (m, 2H, OrnCγ), 1.98 (m, 2H, OrnCꢀ), 3.37 (m, 2H,
OrnCδ), 3.69 (s, 3H, OCH3), 3.93 (m, 1H, AlaCR), 4.21 (m, 1H,
AlaCR), 4.50 (m, 1H, OrnCR), 6.42 (s, 1H, AlaNH), 7.12 (m, 1H,
aromatic), 7.31 (m, 1H, OrnNHCR), 7.35 (s, 1H, AibNH), 7.54 (S,
1H NMR (400 MHz, CDCl3) δ 1.37-1.60 (m, 20H, AibCꢀ,
AlaCꢀ, OrnCꢀ), 1.81 (m, 2H, OrnCγ), 2.03 (s, 3H, Ac), 3.17-3.24
(m, 2H, OrnCδ), 4.02 (s, 1H, OrnCR), 4.11 (m, 1H, AlaCR), 4.41
J. Org. Chem. Vol. 74, No. 9, 2009 3467

Nakayama and Kimura
1H, OrnNHCδ), 7.60 (d, 1H, AlaNH), 7.76 (d, 1H, aromatic), 7.92
(d, 1H, aromatic), 8.22 (s, 1H, aromatic). FAB-MS (matrix: NBA)
Calcd for C32H50IN6O9 [(M + H)+], 789.26; found, 789.3.
Boc-(Ala-Aib)2-Orn(DPE)-OMe (8). To 7 (308 mg, 390 µmol)
and 1,4-diethynylbenzene (59 mg, 468 µmol) in THF were added
Pd(PPh3)2Cl2 (16.5 mg, 23.4 µmol), CuI (7.4 mg, 39 µmol), and
DIEA (272 µL, 1.56 mmol) at 0 °C. The reaction mixture was kept
stirring under an Ar atmosphere for 2 h. The mixture was then
concentrated under reduced pressure. The residue was purified by
a column chromatography (silica gel, chloroform/methanol ) 30/
1), giving 130 mg (165 µmol, 42%).
1H NMR (400 MHz, CDCl3) δ 1.35-1.57 (m, 27H, AibCꢀ, Boc,
AlaCꢀ), 1.75 (m, 2H, OrnCγ), 2.00 (m, 2H, OrnCꢀ), 3.17 (s, 1H,
HCCPh), 3.48 (m, 2H, OrnCδ), 3.71 (s, 3H, OCH3), 3.92 (m, 1H,
AlaCR), 4.17 (m, 1H, AlaCR), 4.52 (m, OrnCR), 4.99 (s, 1H, AlaNH),
6.40 (s, 1H, AibNH), 7.01 (s, 1H, AibNH), 7.31-7.40 (m, 2H,
OrnNHR, aromatic), 7.42-7.51 (m, 5H, AlaNH, aromatic), 7.58
(d, 1H, aromatic), 7.88 (d,1H, aromatic), 8.18 (s, 1H, aromatic).
FAB-MS (matrix: NBA) Calcd for C42H55N6O9 [(M + H)+], 787.40;
found, 787.4.
(m, 4H, OrnCδ), 3.69 (s, 3H, OCH3), 3.92-4.04 (m, 3H, AlaCR,
or OrnCR), 4.13-4.17 (m, 1H, AlaCR, or OrnCR), 4.29 (m, 1H,
AlaCR, or OrnCR), 7.49-8.10 (m, 12H, aromatic). FAB-MS (matrix:
NBA) Calcd for C65H85N12O14 [(M + H)+], 1257.62; found, 1257.7.
Spectroscopy in Solution. CD spectra were measured by a
spectropolarimeter. Optical cells of a 0.1 and 1 cm optical path
length were used. The accumulation number was four. The helix
contents of the peptides were calculated from eq 1.49
fH(%) ) -([θ]222 + 2340) ⁄ 30300
(1)
fH and [θ]222 represent the helix content and molar ellipticity in
residue concentration at 222 nm, respectively. An optical cell of a
1 cm optical path length was used in both absorption and emission
spectroscopic measurements.
Quantum Calculation. ab initio Calculations were carried out
on a Gaussian, Inc. Gaussian 03 program64 using the density
functional theory (DFT) with the Becke’s three parameter hybrid
functional and Lee-Yang-Parr correlation (B3LYP) method65 with
the 6-31G(d,p)66 basis set. The optimized geometry was initially
generated on a Semichem, Inc. Gaussview program,67 then opti-
mized by the DFT method on Gaussian 03. The optimized geometry
was checked by the frequency analysis. It was confirmed that no
imaginary frequency number was outputted. The other geometries
were generated from the optimized geometry by tuning the dihedral
angle between two of the three phenyl rings. TD-DFT method68-70
was used for absorption and electric circular dichroism simula-
tions.71,72 Ten singlet excited states were solved in the calculations.
L-OPE10. To 8 (110 mg, 140 µmol) and 5 (140 mg, 167 µmol)
in THF were added Pd(PPh3)2Cl2 (5.9 mg, 8.4 µmol), CuI (2.7 mg,
14 µmol), and DIEA (97 µL, 560 µmol) at 0 °C. The reaction
mixture was kept stirring under an Ar atmosphere for 3 h. The
reaction mixture was concentrated under reduced pressure. The
residue was purified by a Sephadex LH20 column (eluant: DMF),
giving 106 mg (67.2 µmol, 48% at most). HPLC: retention time )
6.377 min (93%).
1H NMR (400 MHz, CDCl3) δ 1.35-1.59 (m, 45H, AibCꢀ, Boc,
AlaCꢀ), 1.59-1.90 (m, 8H, OrnCꢀ, OrnCγ), 2.07 (s, 3H, Ac),
3.40-3.55 (m, 4H, OrnCδ), 3.71 (s, 3H, OCH3), 3.92 (m, 1H,
AlaCR, or OrnCR), 4.06 (m, 1H, AlaCR, or OrnCR), 4.14 (m, 1H,
AlaCR, or OrnCR), 4.36 (m, 1H, AlaCR, or OrnCR), 4.42 (m,
1H, AlaCR, or OrnCR), 4.51 (m, 1H, AlaCR, or OrnCR), 5.20 (s,
1H, AlaCR, or OrnCR), 5.30 (dd, 2H, OCH2COPh), 6.53 (s, 1H,
NH), 6.88 (s, 1H, NH), 7.00 (d, 1H, NH), 7.35-7.95 (m, 21H,
NH, and aromatic). FAB-MS (matrix: NBA) Calcd for
C78H101N12O18 [(M + H)+], 1493.73; found, 1493.9.
Supporting Information Available: A synthetic scheme,
proton and carbon NMR spectra of L-OPE10 and C-OPE10,
total energies and atom coordinates of 1, 2, R30, and L30. This
material is available free of charge via the Internet at
http://pubs.acs.org.
JO9001905
(64) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Montgomery, J., J. A.; Vreven, T.; Kudin, K. N.;
Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci,
B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada,
M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.;
Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian,
H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.;
Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski,
J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg,
J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.;
Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.;
Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.;
Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill,
P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; and Pople, J. A.
Gaussian 03, Revision E.01; Gaussian, Inc.: Wallingford, CT, 2004.
(65) Becke, A. D. J. Chem. Phys. 1993, 98 (7), 5648–5652.
(66) Ditchfield, R.; Hehre, W. J.; Pople, J. A. J. Chem. Phys. 1971, 54 (2),
724–728.
(67) Dennington, R., II; Keith, T.; Millam, J. GaussView, version 4.1;
Semichem, Inc: Shawnee Mission, KS, 2007.
(68) Stratmann, R. E.; Scuseria, G. E.; Frisch, M. J. J. Chem. Phys. 1998,
109 (19), 8218–8224.
(69) Bauernschmitt, R. d.; Ahlrichs, R. Chem. Phys. Lett. 1996, 256 (4-5),
454–464.
(70) Casida, M. E.; Jamorski, C.; Casida, K. C.; Salahub, D. R. J. Chem.
Phys. 1998, 108 (11), 4439–4449.
(71) Bak, K. L.; Hansen, A. E.; Ruud, K.; Helgaker, T.; Olsen, J.; Jørgensen,
P. Theor. Chim. Acta 1995, 90 (5), 441–458.
(72) Autschbach, J.; Ziegler, T.; van Gisbergen, S. J. A.; Baerends, E. J.
J. Chem. Phys. 2002, 116 (16), 6930–6940.
C-OPE10. L-OPE10 (74 mg, 49 µmol) in methanol (200 µL)
and 1,4-dioxane (200 µL) was treated with 1 N NaOH (60 µL) at
0 °C without stirring for 4 h. The mixture was neutralized with
HCl aq and concentrated under reduced pressure. The product was
treated with trifluoroacetic acid (730 µL) in the presence of anisole
(73 µL) at 0 °C for 1 h. The mixture was concentrated under reduced
pressure, and the residue was washed with diethyl ether. The
identification was carried out by FAB-MS. To the trifluoroacetic
acid salt of the peptide in DMF were added HATU (205 mg, 539
µmol) and 1-hydroxy-7-azabenzotriazole (HOAt; 73 mg, 539 µmol).
The mixture was kept stirring under a N2 atmosphere at 0 °C. To
the solution was added a DMF solution of DIEA (0.1 M, 10.8 mL)
over 1.5 h. The temperature was then gradually raised to room
temperature and the mixture was stirred for 24 h. Additional portions
of HATU (41 mg, 108 µmol), HOAt (14.7 mg, 108 µmol), and
DIEA (28 µL, 162 µmol) were added to the mixture at 0 °C
followed by 33 h of stirring at room temperature. The mixture was
concentrated under reduced pressure and purified by a Sephadex
LH-20 column for two times (eluent: DMF and methanol) and
preparative TLC (eluent: chloroform/methanol 10/1). Finally, the
product was solidified with hexane, giving 10 mg (7.6 µmol, 14%
at most). HPLC: retention time ) 4.713 min (∼100%).
1H NMR (400 MHz, MeOH-d4) δ 1.35-1.57 (m, 36H, AibCR,
AlaCR), 1.75-1.98 (m, 8H, OrnCꢀ, OrnCγ), 2.04 (s, 3H, Ac), 3.48
3468 J. Org. Chem. Vol. 74, No. 9, 2009