Helical Inversion of Peptide-based Supramolecular Co2+ Complexes

Article abstract of DOI:10.1002/bkcs.11540

Herein, we report the helical inversion of supramolecular polymeric complexes of Co²⁺ containing a peptide-based ligand comprising one alanine and three glycine moieties and an achiral terpyridine group. The helicity of the peptide-based supram

Full text of DOI:10.1002/bkcs.11540

Article
DOI: 10.1002/bkcs.11540
BULLETIN OF THE
K. Y. Kim et al.
KOREAN CHEMICAL SOCIETY
Helical Inversion of Peptide-based Supramolecular Co2+ Complexes
†
†
*
Ka Young Kim, Jaehyeong Kim, Hyesong Park, Yeonweon Choi, Ki-Young Kwon,
*
and Jong Hwa Jung
Department of Chemistry and Research Institute of Natural Sciences, Gyeongsang National University,
Jinju 52828, Korea. *E-mail: kykwon@gnu.ac.kr; jonghwa@gnu.ac.kr
Received May 30, 2018, Accepted June 21, 2018
Herein, we report the helical inversion of supramolecular polymeric complexes of Co2+ containing
a peptide-based ligand comprising one alanine and three glycine moieties and an achiral terpyridine group.
The helicity of the peptide-based supramolecular polymer is controlled via strain-induced chirality at dif-
ferent stoichiometric ligand/Co2+ ratios. The supramolecular polymer S-1 adopts octahedral geometry with
right-handed helicity (P-type) in the presence of <0.7 equiv of Co2+. In contrast, it adopts coexisting octa-
hedral and square-pyramidal geometries in the presence of 1.0 equiv of Co2+ and presents left-handed
helicity (M-type). The helicities of the supramolecular polymer R-1 with Co2+, prepared using the chirally
opposite ligand, were completely opposite to those of S-1. Furthermore, the circular dichroism intensities
of supramolecular polymers S-1 and R-1 in the presence of Co2+ were 900–1500 times higher than those
of free S-1 and R-1. In addition, the helical inversion was completely reversible and controllable by the
addition of more Co2+ or ligand.
Keywords: Cobalt complex, Helicity, Supramolecular polymer
Introduction
previous instances, metal-coordinated complexes have also
required chiral ligands to endow them with helicity
(Table 1). In most previous instances, metal-coordinated
complexes have required chiral ligands to endow them with
helicity. For instance, Yashima et al.39 reported the control
of helical chirality in Co2+ and Fe2+ complexes with
2,2-bispyridine-based ligands having chiral or achiral pep-
tide residues. In this instance, the helical chirality of the
metal complexes was controlled by the chirality remote
from metal ions. Furthermore, Miyake et al.10,30,40–42
reported that the left-handed helicity of a peptide-based
ligand containing a racemic pentapeptide in the presence of
Co2+ was converted to right-handed helicity upon the addi-
Controlling helicity in dynamic supramolecular assemblies
is important as it will deepen our understanding of the func-
tion of helicity in biological systems and facilitate the
development of novel chiral materials that can be used to
synthesize and separate enantiomers.1–3 Changeable helicity
is precedented by nature. For instance, the well-known
right-handed double-helical structure of B-form DNA can
undergo inversion under high-salt conditions and upon
chemical modification or complexation with cations and
other chemicals, thereby generating a left-handed Z-form
DNA helix.4–10 Furthermore, an extensive range of syn-
thetic systems exhibit helical conformations.11–13 However,
very few studies investigating the controlled transformation
between different helical senses have been performed.
Examples of synthetic systems that exhibit environment-
responsive helical switching include the solvent-dependent
inversion of helical metal complexes14,15 and dialkylpolysi-
lanes16 as well as the temperature-induced helicity inver-
sion of switchable polyacetylenes,17–21 polydiarylsilanes,22
and polyisocyanates,23–25 among others.26–33
−
−
tion of NO3 . In this instance, the coordination of NO3 to
the Co2+ ions caused the conversion of helicity.
In our previous work, the handedness of supramolecular
polymers based on terpyridine derivatives bearing alanine
and a long cis mono-double-bonded alkyl chain with Co2+
was found to be dependent on the concentration of Co2+.
Specifically, the two helical forms of the complex coexisted
with 0.2–0.8 equiv of Co2+.50 Furthermore, the handedness
of supramolecular Co2+ complexes constructed with
peptide-based ligands was found to be influenced by the
number of peptide residues.51
In this study, the helical inversion of self-assembled
complexes containing peptide-based ligands (scheme 1)
comprising one alanine and three glycine moieties and a
terpyridine moiety as the Co2+ binding site and its helicity
enhancement of an achiral terpyridine moiety are reported.
The helicity inversion of supramolecular R-1 and S-1 com-
plexes with Co2+ occurs upon conversion from octahedral
Various specific noncovalent intermolecular interactions
have been exploited to construct such supramolecular
assemblies.34–38 Among them, the self-assembly of metal
complexes constitutes the main strategy for constructing
supramolecular materials with defined coordination
geometries.39–49 As shown in Table 1, the helicity inversion
was related to the coordination geomertic change. In most
†These authors contributed equally to this work.
Bull. Korean Chem. Soc. 2018, Vol. 39, 988–994
© 2018 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Wiley Online Library
988

Article
BULLETIN OF THE
ISSN (Print) 0253-2964 | (Online) 1229-5949
KOREAN CHEMICAL SOCIETY
Table 1. Previously reported results about the helicity inversion study in metal-coordinated complexes.
Entry
Ligand
Metal ion
Geometry
Helicity
Inverse condition
Ref.
−
1
2
Pentapeptide
Co2+
Co2+
Fe2+
Co2+
6 coordination
6 coordination
From P-form to M-form
From P-form to M-form
Addition of NO3
Addition of Cl−
42
39
2,20-bipyridine
−
3
4
5
N,N0-Ethylenebis
[N-methyl-(S)-alanine]
N,N0-ethylenebis
[N-methyl-(S)-alanine]
Tris(chelate) ligand
bearing two 18-crown
-6 moieties
6 coordination
4 coordination
—
From P-form to M-form
From M-form to P-form
From P-form to M-form
Addition of NO3
Addition of H+
30
10
43
Pd2+
Addition of Et3N
Zn(II)3–La(III)
From P-form to M-form
From P-form to M-form
Control the length
of diammonium guest
6
Macrocycle
Yb(III), Eu(III),
Tb(III)
9 coordination
Change of temperature,
size effect
44
mass spectra were obtained using a JEOL JMS-700 mass
spectrometer. Elemental analyses were performed using a
PerkinElmer 2400 series II instrument.
Preparation of Self-Assembled Structures. A solution of
Co2+ (0.1–1.0 equiv) in tetrahydrofuran (THF) was added
to a solution of R-1 (or S-1) in THF in a vial. Each mixture
was heated for 3 min to form a clear solution and then
allowed to cool to room temperature.
Microscopy Studies. Scanning electron micrographs of
the samples were taken using field-emission scanning elec-
tron microscopy (FE-SEM, Philips XL30 S FEG, JEOL
LTD., Tokyo, Japan). The accelerating voltage was
5–15 kV, and the emission current was 10 μA.
Circular Dichroism Studies.
Circular dichroism
(CD) spectra were recorded in the range 200–500 nm on a
Jasco J-815 CD spectrophotometer using a quartz cell with
a path-length of 0.1 mm. Scans were taken at a rate of
100 nm/min, with a sampling interval of 1.0 nm and a
response time of 1 s. CD spectra of the supramolecular
polymers R-1 or S-1 (8 mM) with Co2+ (0–1.0 equiv) were
observed in THF at room temperature. Pure nitrogen gas
was used to purge the sample holder box to remove oxygen
during the determination.
Scheme 1. Synthesis route of S-1 and R-1.
UV–Vis Studies.
UV–Vis absorption spectra were
to square-pyramidal geometry. Interestingly, the helical
inversion is due to the strain induced in the achiral terpyri-
dine moiety upon complexation with Co2+, not from the S-
or R-form alanine analog component of the ligand.52,53
obtained over the range 200–600 nm using a Thermo Evo-
lution 600 UV–Vis spectrophotometer at room temperature.
The scan rate was 600 nm/min, with a scan interval of
1.0 nm. The UV–Vis absorption bands of supramolecular
polymers R-1 (or S-1) (3 mL, 0.15 μmol, 0.05 mM in
THF) were determined upon addition of Co(NO3)2 (0–1.0
equiv).
Experimental
Characterization. All chemical reagents and solvents
were supplied by Tokyo Chemical Industry (Kumagaya,
Japan), Aldrich (Waltham, MA, USA), or Alfa Aesar
(Heycham, UK). These chemical reagents were used with-
out further purification. The UV–Vis absorption bands of
the supramolecular polymers were determined using a
Thermo Evolution 600 spectrophotometer equipped with a
Vibrational Circular Dichroism Studies. Vibrational cir-
cular dichroism (VCD) spectra were obtained using a
PRESTO-S-2016 VCD-LD spectrometer (JASCO Co. Ltd.,
Tokyo, Japan). The VCD spectrophotometry was combined
with linear dichroism. The machine was calibrated using a
quarter-wave retarder and an analyzer. A sample of the
complex (ca. 0.005 M in THF) was injected into a CaF2-
windowed cell with an optical length of 200 μm. The VCD
signals were obtained using 10 000 scans for each complex.
1
Peltier cell holder for temperature control. The H and 13C
NMR spectra were obtained using a Bruker DRX 300, and
Bull. Korean Chem. Soc. 2018, Vol. 39, 988–994
© 2018 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.bkcs.wiley-vch.de
989

BULLETIN OF THE
Article
Co2+-Triggered Helicity Inversion in a Supramolecular Polymer
KOREAN CHEMICAL SOCIETY
The wavenumber resolution was 4 cm−1. Baseline calibra-
tion of the VCD spectra was performed by subtracting the
solvent contribution.
of 3 (S-form) was performed as described in the same way,
but with 4 (S-form) being used in place of 4 (R-form). H
1
NMR (300 MHz, DMSO‑d6) 8.7 (d, 2H, J = 4.7 Hz), 8.6
(d, 2H, J = 7.9 Hz), 8.0 (m, 5H), 7.9 (d, 1H, J = 7.2 Hz),
7.5 (m, 2H), 7.1 (t, 1H, J = 6.0 Hz), 4.2 (m, 3H), 3.7(d,
2H, J = 5.6 Hz), 3.6 (d, 2H, J = 5.8 Hz) 1.4 (s, 9H), 1.2
(d, 3H, J = 6.5 Hz). 13C NMR (125 MHz, DMSO‑d6)
170.1, 168.9, 167.0, 157.2, 156.4, 155.3, 149.7, 137.9,
125.0, 121.3, 107.3, 78.6, 70.8, 44.4, 43.8, 42.4, 28.7,
17.5. ESI-MS (m/z) calcd. For C27H32N6O5: 520.2;
521.159 [M + H]+. Elemental analysis: calculated for
C27H32N6O5: C 62.3, H 6.2, N 16.1. Found: C 62.0, H 5.8,
N 15.9.
Synthesis of Compound 2. To compound 3 (R-form)
(0.05 g, 0.1 mmol) was added 0.875 mL 1.7 M HCl in
ethyl acetate (previously stirred until homogeneous), and
the mixture was stirred for 2 h. The solution was then
diluted with additional ethyl acetate and water, and NaOH
was added until the solution changed color. The mixture
was extracted with ethyl acetate (3 × 100 mL), the organic
solvents were dried over Na2SO4, and all solvents were
removed using a rotary evaporator. Recrystallization from
ethyl acetate and hexane yielded pure 2 (R-form) in a 56%
yield. The synthesis of 2 (S-form) was performed in the
same way, but by using 3 (S-form) in place of 5 (R-form).
1H NMR (300 MHz, DMSO‑d6) 8.7 (d, 2H, J = 4.7 Hz),
8.6 (d, 2H, J = 7.9 Hz), 8.0 (m, 6H), 7.5 (m, 2H), 4.2 (m,
3H), 3.8 (d, 2H, J = 1.8 Hz), 3.1 (s, 2H), 2.1 (s, 2H), 1.2
(d, 3H, J = 6.4 Hz). 13C NMR (125 MHz, DMSO‑d6)
173.5, 169.0, 167.1, 157.2, 155.3, 149.7, 137.9, 125.0,
121.4, 107.3, 70.8, 45.1, 44.4, 42.2, 17.5. ESI-MS (m/z)
calcd. For C22H24N6O3: 420.2; 421.324 [M + H]+. Elemen-
tal analysis: calculated for C22H24N6O3: C 62.8, H 5.8, N
20.0, Found: C 63.1, H 6.1, N 20.2.
Synthesis of Compound 6.
(3.16 mL, 22.71 mmol) and Boc2O (3.63 g, 16.65 mmol)
were added to suspension of diglycine (2.00 g,
Triethylamine (Et3N)
a
15.14 mmol) ꢀin a mixture of dioxane (60 mL) and H2O
(10 mL) at 0 C. The reaction mixture was maintained with
ꢀ
stirring at 23 C for 16 h. Then, H2O (250 mL) was added,
and the reaction mixture was acidified to pH 3 by the addi-
tion of solid KHSO4. The product was extracted with ethyl
acetate (5 × 50 mL), and residual water in the organic
phases was removed with Na2SO4. Finally, all solvents
were removed using a rotary evaporator to yield product
6 as a white solid without purification. Yield: 3.10 g (88%).
1H NMR (300 MHz, DMSO‑d6) 12.6 (s, 1H), 8.0 (t, 1H,
J = 5.8 Hz), 7.0 (t, 1H, J = 6.0 Hz), 3.8 (d, 2H,
J = 5.8 Hz), 3.7 (d, 2H, J = 6.1 Hz), 1.4 (s, 9H). 13C NMR
(125 MHz, DMSO‑d6) 174.6, 171.0, 156.2, 79.5, 44.6,
42.6, 28.4. ESI-MS (m/z) calcd. For C9H16N2O5: 232.1;
233.004 [M + H]+. Elemental analysis: calculated for
C9H16N2O5: C 46.6, H 6.9, N 12.1. Found: C 46.5, H 7.3,
N 12.1.
Synthesis of Compound 4.
(R or S)-(−)-2-Amino-
1-propanol (0.28 g, 3.7 mmol) was added to a stirred sus-
pension of KOH (1.05 g, 18.7 mmol) in anhydrous DMSO
(20 mL) at 60 ꢀC. After 60 min, 40-chloro-2,20:60,200-
terpyridine (1.00 g, 3.7 mmol) was added to the mixture,
ꢀ
which was maintained with stirring for 4 h at 70 C. Dis-
tilled water (600 mL) was then added to the reaction mix-
ture, and the product was extracted with CH2Cl2
(3 × 200 mL). Residual water in the CH2Cl2 was removed
using Na2SO4, and the CH2Cl2 was removed using a rotary
evaporator. The desired product was recrystallized from
ethyl acetate to give 0.72 g (72%) of 4. 1H NMR
(300 MHz, CDCl3-d) 8.7 (d, 2H, J = 4.7 Hz), 8.6 (d, 2H,
J = 7.4 Hz), 8.0 (m, 4H), 7.5 (m, 2H), 4.0 (m, 2H), 3.2
(dd, 1H, J = 6.3 Hz and J = 12.5 Hz) 1.7 (s, 2H), 1.1 (d,
3H, J = 6.4 Hz). 13C NMR (125 MHz, CDCl3-d) 160.2,
156.5, 154.2, 148.9, 123.7, 120.8, 105.2, 70.1, 48.1, 21.4.
ESI-MS (m/z) calcd. For C18H18N4O: 306.2; 307.307
[M + H]+. Elemental analysis: calculated for C18H18N4O:
C 70.6, H 5.9, N 18.3. Found: C 70.2, H 5.5, N 18.1.
Synthesis of Compound 3. Compounds 4 (R-form) (0.50 g,
1.63 mmol), 6 (0.38 g, 1.63 mmol), 1-ethyl-3-(3-dimethy-
laminopropyl)carbodiimide (EDC, 0.63 g, 3.27 mmol),
4-dimethylaminopyridine (DMAP, 0.42 g, 3.27 mmol), and
NaHCO3 (0.28 g, 3.27 mmol) were added to a 25-mL flask.
Anhydrous dimethylformamide (10 mL) was then injected,
and the reaction mixture was stirred for 2 days at room
temperature. Then solvents were removed using a rotary
evaporator. After the crude product was partitioned in ethyl
acetate/H2O, the organic layer was separated and dried over
Na2SO4. Then, the organic solvent was removed using a
rotary evaporator. Finally, product 5 was recrystallized
from ethyl acetate and hexane. Yield: 62%. The synthesis
Synthesis of Compound S-1. In a two-neck flask, 2 (S-
form) (0.33 g, 0.79 mmol) and triethylamine (0.33 mL,
2.37 mmol) were added to anhydrous CH2Cl2 (75 mL).
The solution was then magnetically stirred, and stearoyl
glycinoyl chloride (1.18 mmol) was added dropwise at
ꢀ
0 C. The reaction mixture was stirred for 17 h; then the
solvents were removed using a rotary evaporator. The crude
product thus obtained was purified by gradient elution chro-
matography on Al2O3 using a mobile phase comprising
CHCl3/MeOH, with the MeOH content changing from 1.0
to 2.0%. The synthesis of R-1 was performed as described
in the synthesis of S-1 but with 2 (R-form) being used in
place of 2 (S-form). Yield: 0.40 g (73%). 1H NMR
(300 MHz, DMSO‑d6) 8.7 (d, 2H, J = 4.9 Hz), 8.5 (d, 2H,
J = 7.8 Hz), 8.2 (t, 1H, J = 5.5 Hz), 8.1(t, 1H, J = 5.4 Hz),
8.0 (m, 4H) 7.9 (d, 1H, J = 7.5 Hz) 7.5 (m, 2H), 4.1 (m,
3H), 3.7 (m, 4H), 3.5 (d, 2H), 2.1 (t, 2H, J = 6.1 Hz), 1.4
(t, 2H, J = 5.8 Hz), 1.2 (m, 31H), 0.8 (t, 3H, J = 6.7 Hz).
13C NMR (125 MHz, DMSO‑d6) 174.3, 171.0, 169.8,
168.2, 167.3, 158.5, 154.9, 148.8, 138.0, 126.3, 120.7,
106.5, 70.7, 43.6, 43.2 42.7, 42.1, 36.2, 31.6, 29.8, 29.9,
29.1, 29.0, 28.7, 24.9, 22.5, 17.5, 14.1. ESI-MS (m/z)
Bull. Korean Chem. Soc. 2018, Vol. 39, 988–994
© 2018 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.bkcs.wiley-vch.de
990

BULLETIN OF THE
Article
Co2+-Triggered Helicity Inversion in a Supramolecular Polymer
KOREAN CHEMICAL SOCIETY
calcd. For C42H61N7O5: 743.47; 744.491 [M + H]+. Ele-
mental analysis: calculated for C42H61N7O5: C 67.8, H 8.3,
N 13.9. Found: C 67.1, H 8.8, N 14.2.
helicity (P-type). The CD spectrum of supramolecular S-1
with <0.7 equiv of Co2+ indicates an octahedral structure,
as confirmed by the ESI-MS measurements. In contrast, the
positive CD signal at 327 nm for supramolecular S-1 was
converted to a negative signal at the same wavelength upon
addition of 1.0 equiv of Co2+ (Figure 2(b)). This result indi-
cates that the P-type helicity of the supramolecular S-1
complex in the presence of Co2+ is inverted to left-handed
(M-type) helicity with square-pyramidal structure.
Results and Discussion
The UV–Vis absorption spectra of S-1 (1.0 × 10−5 M) in
THF are shown in Figure S1(a), Supporting Information. In
the absence of Co2+, absorption bands appear at 275 nm
(ε275 = 3.02 × 104 M−1 cm−1) and 310 nm (ε310 = 4.62
× 103 M−1 cm−1), which correspond to the π–π* and n–π*
transitions, respectively. When Co2+ is added, the absorp-
tion spectrum changes significantly (Figure S1). The inten-
sities of the absorption bands at 275 and 310 increase and a
new absorption band at 320 nm forms. This new band is
due to metal–ligand charge transfer between the terpyridine
moiety of S-1 and Co2+.54,55 Furthermore, the absorption
band at 346 nm exhibits slope changes at 0.5 and 1.0 equiv
of Co2+ (Figure S1(b)). These results indicate that S-1
forms 1:1 and 1:2 (Co2+/S-1) supramolecular complexes
with Co2+ in THF. In addition, a d–d transition absorption
band for supramolecular S-1 complexes with 0.5 and 1.0
equiv of Co2+ was observed. An absorption band for S-1 in
the presence of <0.5 equiv of Co2+ was observed at
490 nm (Figure S1(c) and (d)) resulting in a red coloration,
which is typical of octahedral structures. Conversely, in the
presence of 1.0 equiv of Co2+, the absorption band is
shifted to the longer wavelength of ≈510 nm, resulting in a
pink coloration. These findings clearly indicate that the
original octahedral structure is transformed into a square-
pyramidal structure.56
To obtain more detailed information about the binding of
ligands at different Co2+ concentrations, the effect of Co2+
addition to S-1 was measured via high-resolution ESI-MS.
In the presence of <0.6 equiv of Co2+ (Figure 1(a)) a 1:2
complex peak was observed at m/z = 773.33 for [(S-1)2-
Co]2+, with the UV–Vis spectrum indicating an octahedral
structure. In contrast, 1:1 and 1:2 peaks were observed at
m/z = 697.08 and 773.33 for [S-1-Co-NO3-THF]+ and [(S-
1)2-Co]2+ (Figure 1(b)), respectively, corresponding to
square-pyramidal (1:1 complex) and octahedral structures
(1:2 complex), respectively.
Upon addition of 1.0 equiv of Co2+ to the supramolecu-
lar S-1 solution, the intensity of the CD signal shows a
ca. 1000-fold enhancement due to the well-organized
strain-induced chirality endowed by the formation of a
complex between the terpyridine moiety and Co2+. Thus,
the octahedral structure of supramolecular S-1 at low Co2+
concentrations is changed to a square-pyramidal structure
via helical inversion at high Co2+ concentrations because,
under these conditions, NO3 is bound to Co2+ instead of
−
the terpyridine moiety of S-1.
To examine the influence of the anion effect, the
dynamic helicity of the supramolecular R-1 complex was
observed with and without 0.7 equiv of Co(ClO4)2
(Figure S2). No CD signal is observed for supramolecular
R-1 upon the addition of Co(ClO4)2, unlike in the presence
of Co(NO3)2. This result indicates that the S-1 complex
with Co(ClO4)2 exists as a monomeric species and not as a
supramolecular polymer with a network structure.
To obtain information with respect to helicity conversion
in terms of the d–d transition UV–Vis band at 450–600 nm,
the CD spectra of the supramolecular S-1 complex in the
presence of 0.7 and 1.0 equiv of Co2+ were further observed
(Figure S3). For 0.7 equiv of Co2+, a weak positive CD sig-
nal was observed at ≈490 nm. In contrast, in the presence
of 1.0 equiv of Co2+, the CD signal is opposite to the nega-
tive signal. Compared to the CD signal of supramolecular
S-1 with 1.0 equiv of Co2+, the negative CD signal was
moved to the longer wavelength of ≈510 nm with 1.0 equiv
of Co2+. This absorption band shift for the d–d transition is
further evidence for the geometrical change from an octahe-
dral to a square-pyramidal structure.
By contrast, the CD signal for supramolecular R-1 in
the absence and presence of Co2+ is completely opposite
to that for the supramolecular S-1 complex in the presence
of Co2+. The supramolecular R-1 complex in the presence
of 0.7 equiv of Co2+ presents a negative signal, indicating
M-type helicity, whereas the CD spectra exhibit positive
signals at higher Co2+ concentrations (0.8 equiv,
Figure S4), indicative of P-type helicity. In this instance, a
three-fold decrease in the intensity of the positive CD sig-
nal for supramolecular R-1 in the presence of 1.0 equiv of
Co2+ observed (in comparison with the negative signal
observed for 0.7 equiv of Co2+). These results indicate that
the optical activity of the square-pyramidal conformation
of the R-1 complex with 1.0 equiv of Co2+ in which the
R-1 molecules form a P-type helix is lower than that of
the octahedral conformation.
The CD spectra of supramolecular S-1 and R-1 were
observed in THF with the addition of Co(NO3)2 to deter-
mine their chiroptical properties. Without Co2+, supramo-
lecular S-1 not exhibit a CD signal at 250–350 nm
(Figure 2(a)), even though it contains an S-form alanine
moiety. The supramolecular S-1 presents a positive CD sig-
nal at ≈330 nm upon the addition of Co2+, and this signal
steadily increases with the addition of 0.1–0.7 equiv of Co2
+
without any change in helical direction. The direction of
the CD signal of supramolecular S-1 with <0.7 equiv of
Co2+ was similar to that of the S-form enantiomeric deriva-
tives reported previously. The CD signal was observed as
one band without a shoulder, suggesting that supramolecu-
lar S-1 forms a single complex form with right-handed
Bull. Korean Chem. Soc. 2018, Vol. 39, 988–994
© 2018 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.bkcs.wiley-vch.de
991

BULLETIN OF THE
Article
Co2+-Triggered Helicity Inversion in a Supramolecular Polymer
KOREAN CHEMICAL SOCIETY
Figure 1. ESI mass spectra of S-1 in THF in the presence of (a) 0.5 and (b) 1.0 equiv of Co2+
.
Figure 2. CD spectra of (a) S-1 with several equivalents of Co2+ at room temperature. (b) The plot of CD signal of S-1 at 330 nm against
equivalent of Co2+. [S-1] = 8 × 10−3 M.
To determine which functional moiety of the ligand
decides the helical direction at the supramolecular level, we
measured the chirality of the self-assemblies with Co2+
using VCD spectroscopy (Figures 3 and S5). For S-1 in the
presence of 0.5 equiv of Co2+, the C N stretching band
of the terpyridine moiety shows a positive signal at
1620 cm−1 (Figure 3). In contrast, the sign of the VCD
band for R-1 with Co2+ (0.5 equiv) is opposite to that of S-
1 (Figure S5). These findings indicate that the helical direc-
tion for both S-1 and R-1 in the presence of Co2+ (0.5
equiv) originates from the C N group of the terpyridine,
and not the amide moieties of the peptide. More interest-
ingly, the C N stretching band at 1620 cm−1 for the
supramolecular polymer S-1 with 1.0 equiv of Co2+ was
inverted to a negative signal, indicating that the helicity of
the supramolecular polymer S-1 with 1.0 equiv of Co2+ is
opposite to that of the supramolecular polymer S-1 with 0.5
Figure 3. VCD spectra of S-1 (pink line) and R-1 (blue line) with
(a) 0.5 and (b) 1.0 equiv of Co2+ in THF-d8 at room temperature.
Bull. Korean Chem. Soc. 2018, Vol. 39, 988–994
© 2018 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.bkcs.wiley-vch.de
992

BULLETIN OF THE
Article
Co2+-Triggered Helicity Inversion in a Supramolecular Polymer
KOREAN CHEMICAL SOCIETY
equiv of Co2+. Indeed, the N O and C C stretching
peaks of the supramolecular polymer S-1 with 1.0 equiv of
Co2+ present noteworthy negative VCD signals at 1290 and
1440 cm−1, respectively, which are attributed to terpyridine
strain resulting from the formation of a square-pyramidal
complex between S-1 and Co2+.
By contrast, the VCD spectrum of the supramolecular
polymer R-1 with 1.0 equiv of Co2+ is opposite to that of
R-1 with 0.5 equiv of Co2+ (Figure S5). The C O
stretching bands for S-1 and R-1 in the presence of Co2+
(1.0 equiv) presents no VCD signal around 1650 cm−1. The
handedness of supramolecular S-1 and R-1 in the presence
of Co2+ causes strain for the aromatic group upon complex
formation. However, no VCD signals are observed for the
peptide groups. Thus, from the VCD observations, the
enantiomeric group in the supramolecular polymers S-1
and R-1 formed with Co2+ does not affect the helical
handedness.
complexes in the presence of 0.5 and 0.6 equiv of Co2+ are
in accordance with the CD observations. The fibers with
both right- or left-handed helicities are formed through π–π
stacking between the terpyridine moieties and intermolecular
hydrogen bonds (Figure 4). On the contrary, the supramolec-
ular R-1 complex presents M-type (left-handed) helices
(ca. 355 ꢁ 29 nm pitch) with 0.5 equiv of Co2+ (Figure 4
(c)), whereas this left-handed helicity changes to P-type
(right-handed) with a considerably higher pitch length
(ca. 470 ꢁ 40 nm) at a Co2+ concentration of 1.0 equiv
(Figure 4(d)). In addition, no significant helical differences
in the supramolecular R-1 complexes are observed with >0.7
equiv of Co2+, even though the R-1 complex with 1.0 equiv
of Co2+ can adopt one of two geometries.
Conclusion
We have demonstrated helical inversion in a peptide-based
supramolecular Co2+ polymer that is dependent upon the
concentration of Co2+. Furthermore, the helical inversion of
the supramolecular polymers S-1 and R-1 in the presence
of Co2+ occurs over just one step. The complex exists in
exclusively octahedral geometry at low concentrations of
Co2+ but presents both octahedral and square-pyramidal
geometries with opposite helical directions at high concen-
tration of Co2+. The helicity of these supramolecular com-
plex polymers is controlled by strain-induced chirality upon
the binding of Co2+ by the terpyridine moiety, and not by
the enantiomeric peptide moiety of the ligand. Furthermore,
the helical inversion is completely reversible. This kind of
helicity control in supramolecular polymers in the presence
of metal ions has enormous promise for application in sys-
tems such as redox devices, asymmetric catalysts, helical
probes, and responsive molecular architectures.
To investigate the reversibility of the helical transforma-
tion, the CD spectrum of the self-assembled R-1 complex
(1:1) with Co2+ was recorded with the addition of freer R-
1. The strong negative CD signal at 335 nm becomes a
positive CD signal at a molar ratio of 0.6 (Figure S5). The
inversion of the CD signal indicates a geometric change
involving helicity inversion. Furthermore, the CD intensity
not significantly changed after several cycles of alternate
addition of ligand and Co2+. Thus, the CD inversion is
completely reversible.
To obtain further insight, the morphological changes of
the supramolecular R-1 and S-1 complexes with different
equivalents of Co2+ (0.5 and 1.0 equiv) were observed using
atomic force microscopy (AFM). The AFM image of the
supramolecular S-1 complex with Co2+ (0.5 equiv) shows P-
type (right-handed) helical fiber structures with diameters of
50–150 nm and a helical pitch of ca. 350 ꢁ 50 nm
(Figure 4(a)). In contrast, the AFM image of S-1 clearly
shows M-type (left-handed) helical fiber having a diameter
of 60–250 nm and a helical pitch of ca. 480 ꢁ 35 nm
(Figure 4(b)) with the addition of 1.0 equiv of Co2+ to the S-
1 solution. These helicity changes in the supramolecular S-1
Acknowledgments. This work was supported by the NRF
(2018R1A2B2003637 and 2017R1A4A1014595) supported
by the Ministry of Education, Science and Technology,
Korea. In addition, this work was partially supported by a
grant from the Next-Generation BioGreen 21 Program
(SSAC, Grant no. PJ013186052018), Rural Development
Administration, Korea.
Supporting Information. Additional supporting informa-
tion is available in the online version of this article.
References
1. K. Maeda, D. Hirose, N. Okoshi, K. Shimomura, Y. Wada,
T. Ikai, S. Kanoh, E. Yashima, J. Am. Chem. Soc. 2018,
140, 3270.
2. S. H. Jung, K. Y. Kim, A. Ahn, S. S. Lee, M. Y. Choi,
J. Jaworski, J. H. Jung, New J. Chem. 2016, 40, 7917.
3. S. H. Jung, K. Y. Kim, A. Ahn, M. Y. Choi, J. Jaworski,
J. H. Jung, ACS Appl. Mater. Interfaces 2016, 8, 14102.
Figure 4. AFM images of (a and b) S-1 and (c and d) R-1 with
(a and c) 0.5 and (b and d) 1.0 equiv of Co2+ (scale bar = 1 μm).
Bull. Korean Chem. Soc. 2018, Vol. 39, 988–994
© 2018 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.bkcs.wiley-vch.de
993

BULLETIN OF THE
Article
Co2+-Triggered Helicity Inversion in a Supramolecular Polymer
KOREAN CHEMICAL SOCIETY
4. B. Dumat, A. F. Larsen, L. M. Wilhelmsson, Nucleic Acids
Res. 2016, 44, e101.
5. F. Y.-H. Chen, S. Park, H. Otomo, S. Sakashita,
H. Sugiyama, Artif. DNA PNA XNA 2014, 5, e28226.
6. M. M. Bhanjadeo, A. K. Nayak, U. Subudhi, Biochem. Bio-
phys. Res. Commun. 2017, 482, 916.
32. J. Kumar, T. Nakashima, T. Kawai, Langmuir 2014, 30, 6030.
33. Z. Cheng, K. Li, F. Wang, X. Wu, J. Xiao, H. Zhang,
H. Cao, H. Yang, Liq. Cryst. 2011, 38, 633.
34. C. X. Wang, S. Utech, J. D. Gopez, M. F. J. Mabesoone,
C. J. Hawker, D. Klinger, ACS Appl. Mater. Interfaces 2016,
8, 16914.
7. J. K. Choi, A. D’Urso, M. Balaz, J. Inorg. Biochem. 2013,
127, 1.
35. M. Beyler, V. Heitz, J.-P. Sauvage, B. Ventura, L. Flamigni,
K. Rissanen, Inorg. Chem. 2009, 48, 8263.
8. S. Bae, D. Kim, K. K. Kim, Y.-G. Kim, S. Hohng, J. Am.
Chem. Soc. 2011, 133, 668.
36. H.-B. Yang, K. Ghosh, B. H. Northrop, Y.-R. Zheng,
M. M. Lyndon, D. C. Muddiman, P. J. Stang, J. Am. Chem.
Soc. 2007, 129, 14187.
ꢀ
ꢀ
9. J. Gregolinski, K. Slepokura, J. Lisowski, Inorg. Chem. 2007,
37. S. A. L. Rousseaux, J. Q. Gong, R. Haver, B. Odell,
T. D. W. Claridge, L. M. Herz, H. L. Anderson, J. Am. Chem.
Soc. 2015, 137, 12713.
46, 7923.
10. H. Miyake, M. Ueda, S. Murota, H. Sugimoto, H. Tsukube,
Chem. Commun. 2012, 48, 3721.
38. F. Li, K. G. Yager, N. M. Dawson, Y.-B. Jiang, K. J. Malloy,
Y. Qin, Chem. Mater. 2014, 26, 3747.
11. H. Miyake, K. Yoshida, H. Sugimoto, H. Tsukube, J. Am.
Chem. Soc. 2004, 126, 6524.
39. N. Ousaka, Y. Takeyama, H. Iida, E. Yashima, Nat. Chem.
2011, 3, 856.
40. H. Miyake, H. Sugimoto, H. Tamiaki, H. Tsukube, Chem.
Commun. 2005, 0, 4291.
12. D. D’Alonzo, M. Froeyen, G. Schepers, G. Di Fabio, A. Van
Aerschot, P. Herdewijn, G. Palumbo, J. Guaragna, Org.
Chem. 2015, 80, 5014.
13. Z.-P. Yu, C.-H. Ma, Q. Wang, N. Liu, J. Yin, Z.-Q. Wu,
Macromolecules 2016, 49, 1180.
41. H. Miyake, Symmetry 2014, 6, 880.
42. H. Miyake, H. Kamon, I. Miyahara, H. Sugimoto,
H. Tsukube, J. Am. Chem. Soc. 2008, 130, 792.
43. S. Akine, S. Hotate, T. Nabeshima, J. Am. Chem. Soc. 2011,
133, 13868.
14. C. Merten, R. McDonald, Y. Xu, Inorg. Chem. 2014,
53, 3177.
15. Y. Nagata, T. Yamada, T. Adachi, Y. Akai, T. Yamamoto,
M. Suginome, J. Am. Chem. Soc. 2013, 135, 10104.
16. N. Suzuki, M. Fujiki, R. Kimpinde-Kalunga, J. R. Koe,
J. Am. Chem. Soc. 2013, 135, 13073.
ꢀ
44. J. Gregolinski, J. Lisowski, Angew. Chem. Int. Ed. 2006,
45, 6122.
45. A. El-ghayoury, H. Hofmeier, A. P. H. J. Schenning,
U. S. Schubert, Tetrahedron Lett. 2004, 45, 261.
46. P. Wang, C. N. Moorefield, M. Panzer, G. R. Newkome,
Chem. Commun. 2005, 0, 465.
47. C.-T. Yeung, H.-L. Yeung, C.-S. Tsang, W.-Y. Wong,
H.-L. Kwong, Chem. Commun. 2007, 5203.
17. T. Miyagawa, A. Furuko, K. Maeda, H. Katagiri, Y. Furusho,
E. Yashima, J. Am. Chem. Soc. 2005, 127, 5018.
18. K. Maeda, T. Miyagawa, A. Furuko, H. Onouchi,
E. Yashima, Macromolecules 2015, 48, 4281.
19. S. Sakurai, K. Okoshi, J. Kumaki, E. Yashima, J. Am. Chem.
Soc. 2006, 128, 5650.
48. S. Y.-L. Leung, V. W.-W. Yam, Chem. Sci. 2013, 4, 4228.
49. H. L.-K. Fu, S. Y.-L. Leung, V. W.-W. Yam, Chem. Com-
mun. 2017, 53, 11349.
50. S. H. Park, S. H. Jung, J. Ahn, J. H. Lee, K.-Y. Kwon,
J. Jeon, H. Kim, J. Jaworski, J. H. Jung, Chem. Commun.
2014, 50, 13495.
51. H. Park, K. Y. Kim, S. H. Jung, Y. Choi, H. Sato, J. H. Jung,
Chem. Mater. 2018, 30, 2074.
52. E. Zeller, H. Beruda, A. Kolb, P. Bissinger, J. Riede,
H. Schmidbaur, Nature 1991, 352, 141.
20. Y. Zhou, C. Zhang, Y. Qiu, L. Liu, T. Yang, H. Dong,
T. Satoh, Y. Okamoto, Molecules 2016, 21, 1583.
21. K. Shimomura, T. Ikai, S. Kanoh, E. Yashima, K. Maeda,
Nat. Chem. 2014, 6, 429.
22. K. Tang, M. M. Green, K. S. Cheon, J. V. Selinger,
B. Garetz, J. Am. Chem. Soc. 2003, 125, 7313.
23. G. Maxein, R. Zentel, Macromolecules 1995, 28, 8438.
24. J. Roth, D. J. O’Leary, C. G. Wade, D. Miller,
K. B. Armstrong, J. D. Thoburn, Org. Lett. 2000, 2, 3063.
25. D. Pijper, B. L. Feringa, Angew. Chem. Int. Ed. 2007, 46, 3693.
26. Y. Nagata, R. Takeda, M. Suginome, Chem. Commun. 2015,
51, 11182.
53. D. Chisca, L. Croitor, E. B. Coropceanu, O. Petuhov,
S. G. Baca, K. Krämer, S.-X. Liu, S. Decurtins, H. J. Rivera-
Jacquez, A. E. Masunov, M. S. Fonari, CrystEngComm 2016,
18, 384.
27. Y. Nagata, T. Nishikawa, M. Suginome, J. Am. Chem. Soc.
2014, 136, 15901.
54. J. Fortage, G. Dupeyre, F. Tuyèras, V. Marvaud,
P. Ochsenbein, I. Ciofini, M. Hromadová, L. Pospísil,
A. Arrigo, E. Trovato, F. Puntoriero, P. P. Lainé,
S. Campagna, Inorg. Chem. 2013, 52, 11944.
55. S.-K. Chung, Y.-R. Tseng, C.-Y. Chen, S.-S. Sun, Inorg.
Chem. 2011, 50, 2711.
28. Y. Nagata, T. Kuroda, K. Takagi, M. Suginome, Chem. Sci.
2014, 5, 4953.
29. Y. Yoshinaga, T. Yamamoto, M. Suginome, ACS Macro Lett.
2017, 6, 705.
ꢀ
30. J. Gregolinski, M. Hikita, T. Sakamoto, H. Sugimoto,
H. Tsukube, H. Miyake, Inorg. Chem. 2016, 55, 633.
31. D. Zhao, T. van Leeuwen, J. Cheng, B. L. Feringa, Nat.
Chem. 2017, 9, 250.
56. Y. Inada, N. Hotta, H. Kuwabara, S. Funahashi, Anal. Sci.
2001, 17, 187.
Bull. Korean Chem. Soc. 2018, Vol. 39, 988–994
© 2018 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.bkcs.wiley-vch.de
994