Majority-Rules Effect and Allostery in Molecular Recognition of Calix[4]arene-Based Triple-Stranded Metallohelicates

Article abstract of DOI:10.1002/chem.201800997

The triple-stranded metallohelicates 1 a,/1 b–3 a/3 b possessing internal guest binding cavities surrounded by calix[4]arene units were synthesized through coordination-driven self-assembly. UV/Vis titration experiments verified that the metallohelicates encapsulated N-methyl pyridinium cations bearing amino acid groups to form host–guest complexes. The guest chirality was transferred to the helicity of the helicates through the steric contact between the stereogenic center of the amino acid group and the metal cores. The (M) helicity was induced when guests the (R)-4--(R)-6 were accommodated within the cavities. The multiple guest complexation within the self-assembled helicates 2 a and 3 a displayed large positive cooperative effects, indicating that the first guest complexation preorganizes the rest of the cavities to facilitate a subsequent guest binding. This cooperativity results in the majority-rules effect in the chiral guest binding for 2 a and 3 a.

Full text of DOI:10.1002/chem.201800997

A Journal of
Accepted Article
Title: Majority-Rules Effect and Allostery in Molecular Recognition of
Calix[4]arene-Based Triple-Stranded Metallohelicates
Authors: Yutaro Yamasaki, Hidemi Shio, Tomoko Amimoto, Ryo
Sekiya, and Takeharu Haino
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.201800997
Link to VoR: http://dx.doi.org/10.1002/chem.201800997
Supported by

10.1002/chem.201800997
Chemistry - A European Journal
FULL PAPER
Majority-Rules Effect and Allostery in Molecular Recognition of
Calix[4]arene-Based Triple-Stranded Metallohelicates
Yutaro Yamasaki,[a] Hidemi Shio,[a] Tomoko Amimoto,[b] Ryo Sekiya,[a] and Takeharu Haino*[a]
Dedication ((optional))
Abstract: The triple-stranded metallohelicates 1a,b–3a,b possessing
the internal guest binding cavities surrounded by the calix[4]arene
units were synthesized via the coordination-driven self-assembly. The
UV/vis titration experiments verified that the metallohelicates
encapsulated the N-methyl pyridinium cations bearing the amino acid
groups to form the host-guest complexes. The guest chirality was
transferred to the helicity of the helicates through the steric contact
between the stereogenic center of the amino acid group and the metal
cores. The (M)-helicity was induced when guests (R)-4–(R)-6 were
accommodated within the cavities. The multiple guest complexation
within the self-assembled helicates 2a and 3a displayed large positive
cooperative effects, indicating that the first guest complexation
preorganizes the rest of the cavities to facilitate the subsequent guest
binding. This cooperativity results in the majority-rules effect in the
chiral guest binding for 2a and 3a.
and co-workers reported on a structurally characterized double-
stranded metallohelicate using a bipyridine-copper(I) coordination
bond.[10] Since then, metallohelicates have been actively
investigated.[11],[12] The groups of Raymond,[13] Stack,[14]
Albrecht,[15]
and
Hahn[16]
synthesized
triple-stranded
metallohelicates formed through the self-assembly of catechol
ligands with metal ions. The labile coordination bonds permit the
dynamic interconversion between left-handed (M)- and right-
handed (P)-forms, which can be biased by chiral guest
complexation to the exterior of the helicates.[17] Despite the many
examples of self-assembled multinuclear metallohelicates
possessing conformationally coupled metal cores,[18] a limited
number of majority-rules and allosteric effects have been
demonstrated in the molecular recognition of multinuclear
metallohelicates due to the lack of binding cavities large enough
to encapsulate the sizable chiral guests.[19] Extended helicates
possessing multiple guest-binding cavities are of particular
interest (Figure 1a). Encapsulation of chiral guests in one of the
cavities can bias the handedness of the helicates, and
simultaneously regulate the rest of the cavities to drive the
Introduction
Helical structures are ubiquitous in nature.[1] Tobacco mosaic
virus,[2] F-actin,[3] DNA,[4] and the α-helix peptide sequence[5] are
typical examples of helical organization in a range of sizes
extending from the nanometer to micron scales. These helical
structures are key structural motifs that play a crucial role in the
regulation of physiological functions.[6] Much effort has been
devoted to mimicking the helical structures of biopolymers with
artificial supramolecules and macromolecules in order to obtain
unique photochemical and catalytic properties.[7] Compared to the
single chain helical structures,[8] multi-stranded helical structures
have been studied to a lesser extent due to the difficulties in their
synthesis. Therefore, additional non-covalent interactions such as
hydrogen bonding interaction, p-p stacking interaction, and
dipole-dipole interaction are required to direct multi-stranded
helical organizations.[9]
positive cooperativity for the inclusion of another guest.
(a)
R
R
R
S
R1
(3n + 6)K+
R1
(b)
R1
R1
R1
R1
R1
R1
O
O
N
H
N
H
O
H
NH
NH
H
O
1
N
R
1
O
O
R
N
O
O
O
O
O
O
O
O
O
O
O
O
O
1
M
M
O
M
O
O
1
R
O
O
O
R
O
1
1
R
R
HN
HN
O
HN
H
N
O
HN
N
H
A
coordination-driven self-assembly has become an
1
R
1
R
R1
O
R1
O
R1
alternative approach for the construction of multi-stranded helical
structures, the so-called “metallohelicate.” In seminal work, Lehn
R1
R1
R1
R1
R1
n
R1 = OPr
3+
3+
3+
3+
3+
3+
1a : n = 0, M = Fe
2a : n = 1, M = Fe
3a : n = 2, M = Fe
1b : n = 0, M = Ga
2b : n = 1, M = Ga
3b : n = 2, M = Ga
[a]
[b]
Y. Yamasaki, H. Shio, Prof. Dr. R. Sekiya, Prof. Dr. T. Haino
Department of Chemistry,
Graduate School of Science, Hiroshima University,
1-3-1 Kagamiyama, Higashi-Hiroshima, 739-8526 Japan
E-mail: haino@hiroshima-u.ac.jp
2
2
4
5 :
6
7
: R = –CH2CH(CH3)2
O
R
O
2
R
R
= –CH2Ph
= –CH3
N
H
COOMe
N
H
COOMe
8
2
2
:
T. Amimoto
+
N
—
PF
6
Natural Science Center for Basic Research and Development,
Hiroshima University,
: R = –H
1-3-1 Kagamiyama, Higashi-Hiroshima 739-8526, Japan
Figure 1. (a) Schematic representation of preorganization of conformationally
coupled guest-binding cavities through guest encapsulation. (b) Structures of
triple-stranded metallohelicates 1a,b, 2a,b, and 3a,b and guests 4–8.
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
This article is protected by copyright. All rights reserved.

10.1002/chem.201800997
Chemistry - A European Journal
FULL PAPER
PrO
PrO
OPr
OPr
OPr
PrO
OPr
PrO
a
O
O
HN
R
H2N
NH
R
NH2
9
R
R
10: R = OBn
L1: R = OH
b
c
PrO
OPr
PrO
OPr
PrO
OPr
PrO
OPr
OPr
PrO
OPr
PrO
d
f
O
O
NH
R
NH2
O
NH
R
HN
O
NH
O
HN
11: R = OBn
R
R
R
12: R = OBn
L2: R = OH
R
R
e
R
PrO
OPr
PrO
OPr
PrO
PrO
PrO
PrO
OPr
PrO
OPr
OPr
OPr
PrO
OPr
OPr
g, h
O
O
O
HN
NH
O
NH
HN
HN
NH
O
NH
HN
R
R
O
O
O
R
R
R
R
R
R
14: R = OBn
L3: R = OH
COOBn
BnOOC
R
R
i
13: R = OBn
R
R
Scheme 1. Synthesis of L1, L2, and L3. Reagents and conditions: (a) 2,3-bis(benzyloxy)benzoic acid, EDC, HOBt, DMF, 85%; (b) H2, Pd/C, 25% AcOEt–THF,
89%; (c) 2,3-bis(benzyloxy)benzoic acid, EDC, HOBt, DMF, 21%; (d) 2,3-bis(benzyloxy)telephthalic acid, EDC, HOBt, DMF, 77%; (e) H2, Pd/C, 25% AcOEt–THF,
88%; (f) 2,3-bis(benzyloxy)telephthalic acid monobenzyl ester, EDC, HOBt, DMF, 63%; (g) LiOH, 30% H2O–THF, 69%; (h) 11, EDC, HOBt, DMF, 87%; (i) H2, Pd/C,
THF, 67%.
We have previously reported a D3-symmetric dinuclear triple-
stranded helicates 1a,b composed of trivalent metal ions and di-
anionic form of C2-symmetric calix[4]arene-based bis-bidentate
ligands L1 (Scheme 1).[20] Herein, we report the synthesis and the
biscalix[4]arene 12, which was subjected to hydrogenolysis in the
presence of Pd/C under hydrogen atmosphere to furnish L2 in
good yield. L3 was also prepared from compound 9. The
condensation reaction of
9 with two equivalents of 2,3-
molecular
recognition
of
multinuclear
triple-stranded
bis(benzyloxy)telephthalic acid monobenzyl ester afforded the
disubstituted calix[4]arene 13 in 63% yield. The hydrolysis of 13
with LiOH, and the following condensation reaction with two
equivalents of 11 resulted in triscalix[4]arene 14 in 60% yield. The
hydrogenolysis of 14 in the presence of Pd/C under hydrogen
atmosphere afforded L3 in good yield.
supramolecular helicates 1a,b, 2a,b, and 3a,b possessing one,
two and three guest-binding cavities (Figure 1b). The N-
methylpyridinium guests 4–7 bearing chiral amino acids were
captured into the cavities. The conformationally coupled multiple
cavities of 2a and 3a displayed strong cooperativity in the guest
binding. The guest chirality was effectively transferred to the
helical senses of the helicates through the steric interaction
between the cavities and the stereogenic centers of the guests.
Majority-rules effects were found in the guest binding for helicates
2a and 3a.
Coordination-Driven Self-Assembly
The deprotonation of L1, L2, and L3 with KOH in methanol gave
the anionic ligands L12–, L23–, and L34–, which were treated with
Fe(acac)3 or Ga(acac)3. The absorptions of K2L1, K3L2, and K4L3
appeared approximately at 290 nm (Figures 2a,b,c). The addition
of Fe(acac)3 decreased the intensity of the absorption bands, and
new absorption bands emerged in the ranges of 270–280 nm and
520–600 nm with isosbestic points for L12–, L23–, and L34–. The
visible absorption bands correspond to the ligand-to-metal charge
transfer (LMCT) in the [tris(catecholato)iron(III)]3– complexes,
which are responsible for the formation of the self-assembled
metallohelicates.[22] The metal-ligand stoichiometric ratios for 1a,
2a, and 3a were determined using a Job plot (Figure 2d). The plot
showed the peaks appearing at the mole ratios of 3:2, 1:1, and
3:4 for K2L1, K3L2, and K4L3, respectively, confirming the
formation of the triple-stranded helicates 1a, 2a, and 3a.
Results and Discussion
Synthesis of calix[4]arene ligands
The syntheses of ligands L1–L3 are outlined in Scheme 1. Ligand
L1 was prepared from 5,17-diaminocalix[4]arene 9[21] in
accordance with our previously reported method.[20] The
condensation reaction of 9 and 2,3-bis(benzyloxy)benzoic acid
gave the protected calix[4]arene 10, which was deprotected to
afford the monomeric ligand L1 in excellent yield. Ligand L2 was
synthesized from 9. The mono-substituted calix[4]arene 11 was
produced through the condensation of 9 with one equivalent of
2,3-bis(benzyloxy)benzoic acid. The treatment of 11 with 0.5
equivalents of 2,3-bis(benzyloxy)telephthalic acid gave
This article is protected by copyright. All rights reserved.

10.1002/chem.201800997
Chemistry - A European Journal
FULL PAPER
R
(a)0.4
(b)
R
(a)
d
O
e
f
NH
c
0.5
b
O
a
a
He
Ga
a
e
O
Hb
f
Hc
Ha
Hd
Hf
at 323K
0
0
400
Wavelength / nm
800
400
Wavelength / nm
800
(c)
(d)1.0
at 233K
6.0
1.0
7.0
δ / ppm
RR
R
R
R
R
a
(b)
d
k
e
e
g
O
h
l
i
j
NH
f
NH
HN
m
c
0
0
O
O
400
Wavelength / nm
800
O
b
0
0.5
1.0
[L] / ([L] + [Fe3+])
O
O
Ga
a
O
Ga
,
He Hg
Hd,Hh
Hl
Figure 2. Changes in the UV/vis absorption spectra of (a) K2L1 (2.0 × 10–5 mol
L–1) with Fe(acac)3 (a–e: 0.0, 0.34, 0.68, 1.02, 1.34 × 10–5 mol L–1), (b) K3L2 (2.0
× 10–5 mol L–1) with Fe(acac)3 (a–f: 0.0, 0.4, 0.8, 1.2, 1.6, 2.0 × 10–5 mol L–1),
and (c) K4L3 (2.0 × 10–5 mol L–1) with Fe(acac)3 (a–e: 0.0, 0.67, 1.3, 2.0, 2.7 ×
10–5 mol L–1) in methanol at 298 K. (d) Job plots of K2L1 (filled circles), K3L2
(crosses), and K4L3 (open circles) with Fe(acac)3 in methanol. The total
concentration of the ligands and [Fe(acac)3] was maintained at 2 × 10–5 mol L–
Hj
Hk
Hc,Hi
Hb
Hm
Hf Ha
at 323K
at 233K
1
.
8.0
7.0
δ / ppm
Figure 3. 1H NMR spectra of (a) 1b and (b) 3b in methanol-d4.
To gain detailed structural insights into metallohelicates 1a–
3a using 1H NMR spectroscopy, Ga(III) ion was employed instead
of Fe(III) ion in order to avoid the paramagnetic line broadening.
Figure 3 displays the sharp 1H NMR spectra of helicates 1b and
3b at 323 K, while 2b gave rise to an ill-defined broad NMR
spectrum. 1H NMR spectrum of 1b showed the presence of a
single compound in the solution. The aromatic protons Ha–Hf
appeared as fairly sharp signals, showing the signatures of a D3h-
symmetric structure due to the rapid exchange between the Δ,Δ-
form and the Λ,Λ-form.[13a] The 1H NMR spectrum was
temperature-dependent. Upon cooling the solution, the
interconversion of the Δ,Δ- and Λ,Λ-forms became slow on the
NMR timescale, and 1b exhibited two sets of the calixarene
aromatic protons Hd–Hf at 233 K. The energetic barrier of 52.1 kJ
mol–1 was determined at the coalescence temperature (Tc) of 273
K for Hd (Fig. S30). The 1H NMR spectrum of metallohelicate 3b
at 323 K also suggests the D3h symmetry of the structure.
Although the catechol protons Ha–Hc, Hi, and Hj were well-
resolved and sharp at 323 K, the calixarene aromatic protons Hd,
Hf, and Hh were fairly broadened, implying that the
interconversion process between the helical Δ,Δ,Δ,Δ-form and the
Λ,Λ,Λ,Λ-form is slower than that of 1b. Cooling the solution led to
the two sets of the calixarene aromatic protons Hd–Hh and Hk–
Hm below 300 K. The energetic barrier of 64.5 kJ mol–1 was
determined at Tc of 293 K for Hd (Fig. S32). The activation energy
of 3b is only 1.2 times as large as that of 1b although the number
of the metal cores for 3b is the double of those for 1b. These
findings suggest that each tris(catecholato)gallium(III) core in 3b
may be fairly independent in the interconversion process between
the Δ-form and Λ-form, as reported by Raymond and co-
workers.[13d]
(a)
(b)
13 Å
L1
L2
5
1b
L3
19 Å
32 Å
13 Å
2b
3b
13 Å
2
7
5
3
1
δ
/ ppm
47 Å
Figure 4. (a) 2D DOSY spectra of L1, L2, L3, 1b, 2b, and 3b in methanol-d4 at
ambient temperature. (b) Energy minimized structures of (M)-1b, (M)-2b, and
(M)-3b. Hydrogen atoms are omitted for clarity.
Diffusion-ordered NMR spectroscopy (DOSY) is known to be
useful for the examination of the size of molecular assemblies in
solution. The use of the DOSY technique allows us to obtain
molecular diffusion coefficients that estimate the hydrodynamic
radii of either a molecule or a molecular assembly.[23] Figure 4a
shows 2D DOSY spectra of ligands L1–L3 and metallohelicates
1b–3b. One sets of the signals was observed, showing that the
self-assembly of the ligands with the Ga(III) ions resulted in the
uniform complexes without any polymeric aggregates.
This article is protected by copyright. All rights reserved.

10.1002/chem.201800997
Chemistry - A European Journal
FULL PAPER
calcd
obs
(a)
(b)
–
[1a – 6K+ – 2L14– – Fe3+
]
calcd
–
[1b – 6K+ – 2L14– – Ga3+
]
2–
[1a – 6K+ – L14–
]
obs
1392
1396
1406
1410
[1a – 6K+ – L14– – Fe3+ + 4H+]–
[1b – 6K+ – L14– – Ga3+ + 4H+]–
[1a – 6K+ + 4H+]2–
[1b – 6K+ + 4H+]2–
1000
2000
1000
2000
m/z
m/z
calcd
calcd
(c)
(d)
[2a – 9K+ – 2L26– – 2Fe3+ + 2H+]–
[2b – 9K+ – 2L26– – 2Ga3+ + 2H+]–
obs
obs
2595
2600
2616
2620
[2a – 9K+ + 7H+]2–
[2a – 9K+ – L26– – Fe3+ + 5H+]–
[2b – 9K+ – L26– – Ga3+ + 5H+]–
[2b – 9K+ + 7H+]2–
2000
3000
2000
3000
m/z
m/z
calcd
calcd
[3b – 12K+ – 2L38– – 3Ga3+ + 3H+]2–
[3a – 12K+ – 2L38– – 3Fe3+ + 3H+]2–
(e)
(f)
2–
[3b – 12K+ – 2L38– – 2Ga3+
]
2–
[3a – 12K+ – 2L38– – 2Fe3+
]
obs
obs
[3b – 12K+ – L38– – 2Ga3+ + 7H+]3–
[3a – 12K+ – L38– – 2Fe3+ + 7H+]3–
1900
1903
1913
1916
[3a – 12K+ – L38– – Fe3+ + 4H+]3–
[3a – 12K+ + 8H+]4–
[3b – 12K+ – L38– – Ga3+ + 4H+]3–
[3b – 12K+ + 8H+]4–
1000
2000
m/z
1000
2000
m/z
Figure 5. ESI-MS spectra of (a) 1a, (b) 1b, (c) 2a, (d) 2b, (e) 3a, and (f) 3b. Insets indicate the (red) calculated and (black) observed isotopic distributions.
Diffusion coefficients of 4.07(2) × 10–10, 3.06(3) × 10–10, and
2.366(6) × 10–10 m2 s–1 calculated for 1b, 2b, and 3b at 293 K are
Table 1. Diffusion coefficients (D), hydrodynamic radii (rh), equivalent radii
(req), shape factors (f(p)), geometrical factors (p), and ratios of semi-major
axes (a) and semi-minor axes (b) of the optimized structures 1b, 2b, and 3b.
obviously smaller than those of 6.64(6) × 10–10, 5.82(8) × 10–10
,
and 3.95(6) × 10–10 m2 s–1 for L1, L2, and L3. These findings
confirm that metallohelicates 1b, 2b, and 3b are large compared
to the corresponding ligands. Assuming that all the helicates are
spherical, the hydrodynamic radii (rh) of the metallohelicates 1b,
2b, and 3b were calculated from the diffusion coefficients by the
Stokes-Einstein equation, D = kBT/(6πηrh) (kB is the Boltzmann
constant and η is the viscosity of methanol at 293 K). The
hydrodynamic radii (rh) of 8.9, 11.8, and 15.3 Å for 1b, 2b, and 3b
were proportional to the number of the calixarene cores. However,
the hard sphere approximation may be valid only for helicate 1b,
whereas helicates 2b and 3b are obviously non-spherical. The
modified Storks-Einstein equation, D = kBT/(cf(p)πηrh) (c is a size
correlation factor and f(p) is the shape correlation factor) takes
into account deviation from the hard sphere approximation.[24]
When the helicates are considered as prolate ellipsoids, their
diffusions can provide detailed insights into ellipsoidal dimensions
with the shape correction factors f(p), resulting in the geometrical
factor p, which is a ratio of the semi-major axis a and the semi-
minor axis b (Table 1).[25]
Helicates
D / 10–10
rh / Å
req / Å
f(p)
p
a/b
m2 s–1
1b
2b
3b
4.07(2)
3.06(3)
2.366(6)
9.08
12.0
15.4
8.98
11.1
12.7
0.99
0.93
0.83
1.4
2.4
4.4
1.5
2.5
3.6
Molecular mechanics calculation of
a
supramolecular
complex enables the visualization of its size, shape, and
dimensions. For greater insight, the structures of metallohelicates
1b, 2b, and 3b were calculated by MacroModel V9.1 using the
AMBER* force field.[26] Figure 4b displays the energy-minimized
structures of 1b, 2b, and 3b, which are obviously cigar-like
ellipsoids. The stable structures of the triple-stranded
metallohelicates possess 3-fold rotational axes through the Ga3+
centers. Each monomer unit was twisted with the angle of
approximately 155°, giving rise to the pseudo D3-symmetric triple-
stranded structures. Each metal ion adopts the Δ-configuration in
the (P)-conformers and the Λ-configuration in the (M)-conformers.
Base on the molecular volumes of the optimized structures, the
This article is protected by copyright. All rights reserved.

10.1002/chem.201800997
Chemistry - A European Journal
FULL PAPER
spherical equivalent radii (req) were calculated (Table 1). For all
the helicates, reqs are slightly smaller than rhs, which yields shape
factors (f(p)) of 0.99–0.83, and the geometrical factors (p) of 1.4–
4.4 for 1b, 2b, and 3b. The molecular dimensions of 1b, 2b, and
3b were shown in Figure 4b. The ratios of semi-major and semi-
minor axes for the optimized structures are in fair agreement with
the geometrical factors (p). Accordingly, helicates 1b, 2b, and 3b
behave in solution as cigar-like ellipsoids with dimensions very
similar to those found in the optimized structures.
therefore, the intermolecular CH/π interaction of the acidic N+–
CH3 protons within the cavity of 1b primarily drives the host-guest
complexation. The multiple guest-binding cavities of 2b and 3b
encapsulated the methyl pyridinium ring of (R)-4 (Figure 6b). The
pyridinium protons Hb,c shifted upfield in the presence of 1b, 2b,
and 3b, while the upfield shifts for the methyl ester proton Hf were
negligible.
i-Bu
(a)
O
a
b
f
OMe
Mass spectrometry provides evidence for the formation of the
metallohelicates in the gas phase.[27] Metallohelicates 1a,b, 2a,b,
and 3a,b can be negatively charged upon being infused into the
mass analyzer. The ESI-MS spectra of 1a and 1b gave rise to the
most abundant peaks of 1394.02 and 1408.01, corresponding to
[1a – 6K+ + 4H+]2– and [1b – 6K+ + 4H+]2–, respectively. The ligand
fragmentation occurred easily in the gas phase, resulting in [1a,b
– 6K+ – L14– – M3+ + 4H+]– and [1a,b – 6K+ – 2L14– – M3+]–.
Helicates 2a and 2b were successfully ionized to produce the
divalent molecular ions of [2a – 9K+ + 7H+]2– and [2b – 9K+ + 7H+]2–,
emerging at 2598.03 and 2619.02, respectively, with a certain
amount of the fragment ions of [2a,b – 9K+ – L26– – M3+ + 5H+]–
and [2a,b – 9K+ – 2L26– – 2M3+ + 2H+]–. In the ESI-MS spectra of
3a and 3b, the tetravalent molecular ions of 3a and 3b were
successfully detected as weak peaks of 1900.52 and 1914.26,
corresponding to [3a – 12K+ + 8H]4– and [3b – 12K+ + 8H]4–,
respectively. However, many ligand-fragmented ions of [3a,b –
12K+ – L38– – M3+ + 4H+]3–, [3a,b – 12K+ – L38– – 2M3+ + 7H+]3–,
[3a,b – 12K+ – 2L38– – 2M3+]2–, and [3a,b – 12K+ – 2L38– – 3M3+
+ 3H+]2– were simultaneously detected, most likely due to the
highly charged nature of the molecular ions. All ESI-MS
measurements provided the well-resolved peaks of the molecular
ions and their ligand-fragmented ions which were in good
agreement with their calculated isotope distributions, confirming
the formation of the metallohelicates in the gas phase. The ligand-
fragmented ions observed in all MS spectra suggest that the
metallohelicates are most likely labile due to the reversible
coordination bonds of the tris(catecholato)iron or the gallium
complex.
N
H
c
e
O
N
d
Hc He Hb
9.0
Hd
Hf
Ha
4.0
δ / ppm
3.0
2.0
(b)
0.5
0
0
0.4
[helicate] / mmol L–1
Figure 6. (a) 1H NMR of guest (R)-4 (1.0 × 10–3 mol L–1) in the presence of 1b
(from bottom to top: 0, 1.0, 2.0, 3.0, 5.0 × 10–4 mol L–1) at 298 K in methanol-d4.
(b) Chemical shift changes of protons Hb (filled circles), Hc (filled rhombuses),
and Hf (crosses) of (R)-4 (1.0 × 10–3 mol L–1) in the presence of helicates 1b
(red), 2b (blue), and 3b (black).
Guest Complexation
To examine the formation of host-guest complexes, the
methyl pyridinium guests 4–7 bearing amino acid esters were
employed. 1H NMR titration experiment of (R)-4 were carried out
with 1b (Figure 6a). Upon the addition of 1b, the aromatic protons
Hb, Hc, He, and the two methyl protons Ha, Hd of the pyridine ring
exhibited upfield shifts, while no upfield shift of the methyl ester
group was observed. These results indicate that the N-methyl
pyridinium ring was selectively accommodated within the cavity of
1b, experiencing the shielding effect of the aromatic rings of the
three calix[4]arene units, and the ester methyl group remained
outside the cavity. The acidic N+–CH3 protons of (R)-4 should
participate in the host-guest complexation through the
intermolecular CH/π interaction in the π–basic cavity. To confirm
the contribution of the CH/π interaction, the reference guest 8,
which does not possess any positively charged methyl moieties
on the aromatic rings, was titrated with 1b instead of guest (R)-4.
No change was observed in the chemical shifts of their protons;
(a)
(b)
N-H•••O=C
H-bonding
Figure 7. (a) Top view and (b) side view of the calculated structure of the host-
guest complex (R)-4⊂1b.
Molecular mechanics calculations are helpful for
understanding the intermolecular association of the host-guest
This article is protected by copyright. All rights reserved.

10.1002/chem.201800997
Chemistry - A European Journal
FULL PAPER
complex (R)-4⊂1b. The conformational search was carried out
using low-mode search algorithm[28] to generate 1000 initial
geometries, which were then optimized using the AMBER* force
field. Two low-energy host-guest structures with similar
characteristics are found to be within 12 kJ mol–1 of each other.
The most stable conformation is shown in Figure 7. The N-methyl
group stays in one of the calixarene cavities, which evidences the
presence of the CH/π interaction. The guest amide N-H is
hydrogen-bonded to one of the amide carbonyl group of the host,
and the ester carbonyl group of the guest is directed at the N-H
proton of the host to form the hydrogen bond. These attractive
intermolecular CH/π and hydrogen-bonding interactions most
likely drive the intermolecular association between 1b and the
cationic guests. In addition, the stereogenic carbon of the guest is
located on the catechol ring. This close contact of the stereogenic
carbon to the stereogenic metal center of 1b most likely drives the
one-handed helical structure of 1b.
1:3 for 1a, 2a, and 3a, respectively, are perfectly matched with the
number of the guest binding cavities of the helicates; thereby, all
cavities of the metallohelicates are capable of encapsulating the
guest molecules. The experimental spectra were elaborated with
the HypSpec program,[29] and subjected to a non-linear global
analysis by applying 1:1 and 1:2 host-guest models of binding to
determine the association constants for 1a and 2a. The binding
constants of 1a and 2a for guests 4–7 are shown in Table 2. Upon
the application of the 1:3 host-guest model of binding for 3a, the
binding constants (K1–K3) were not directly obtained. A non-linear
global analysis was repeatedly carried out with the arbitrary K1
values estimated based on the results for 1a and 2a until the
residual errors reached the smallest possible values.
Metallohelicates 1a, 2a, and 3a encapsulate guests 4–7
bearing the amino acid side chains with the large binding
constants in the range of 103–104 L mol–1. The first guest binding
into the cavities of the helicates was gradually facilitated from 1a
to 3a, most likely implying that the cavities become structurally
preorganized as increasing the number of the metal centers. The
alkyl substituents of the amino acid side chains strongly
influenced the guest binding. The steric interaction of the benzyl
group for 5 is likely to be repulsive to the exterior of the cavities
(entry 7 and 10 versus 4; 8 and 11 versus 5; 9 and 12 versus 6).
By contrast, the iso-butyl group may result in the attractive
interaction to the aromatic exterior of the helicates (entry 2 versus
8 and 11; 3 versus 9 and 12).
Determination of Binding Constants
1.0
(a)
(b)
h
a
h
a
1.0
Table 2. Binding constants of metallohelicates 1a, 2a, and 3a with (R)-4,
(R)-5, (R)-6, and 7.
0
400
0
800
400
800
Wavelength / nm
Wavelength / nm
(c)
(d) 1.0
entry
1
Guest
Host
1a
2a
3a
1a
2a
3a
1a
2a
3a
1a
2a
3a
K1 / L mol–1
2.99(2) × 103
7.48(8) × 103
7.94 × 103a
K2 / L mol–1
—
K3 / L mol–1
(R)-4
—
2.0
h
a
2
8.4(1) × 103
9.15(5) × 103
—
—
3
5.04(3) × 103
4
(R)-5
(R)-6
7
1.32(1) × 103
1.72(3) × 103
2.34 × 103a
—
0
400
0
800
0
0.5
1.0
Wavelength / nm
5
2.45(5) × 103
5.1(1) × 103
—
—
[H] / ([H] + [G])
6
5.8(1) × 103
Figure 8. UV/vis absorption spectra of (a) 1a (1.0 × 10–4 mol L–1), (b) 2a (1.0 ×
10–4 mol L–1), and (c) 3a (1.0 × 10–4 mol L–1) upon the addition of (R)-4 (a–h: (a)
0.0, 0.98, 1.9, 3.3, 4.6, 6.1, 8.0, 10.0 × 10–4 mol L–1; (b) 0.0, 0.98, 1.9, 2.8, 3.7,
5.0, 6.9, 10.0 × 10–4 mol L–1; (c) 0.0, 1.9, 3.2, 4.1, 5.3, 6.5, 8.0, 10.0 × 10–4 mol
L–1) in methanol at 298 K. (d) Job plots of 1a (filled circles), 2a (crosses), and
3a (open circles) with (R)-4 in methanol. The total concentration of the helicates
7
3.58(4) × 103
4.00(5) × 103
4.12 × 103a
—
8
6.9(1) × 103
4.6(1) × 103
—
—
9
1.4(1) × 104
and (R)-4 was maintained to be 1.0 × 10–4 mol L–1
.
10
11
12
5.11(3) × 103
3.10(7) × 103
6.31 × 103a
—
2.70(8) × 103
5.1(1) × 103
—
To discuss the cooperative effects for the conformationally
coupled multiple cavities, the guest binding abilities of 1a, 2a, and
3a were evaluated using UV/vis absorption spectroscopy. The
tris(catecholato)iron(III) cores provide the LMCT band in the
visible region, which was quite sensitive for guest binding (Figures
8a,b,c). When (R)-4 was added into the solutions of 1a, 2a, and
3a, the broad band at approximately 700 nm gradually decreased,
and new bands at approximately 500 nm emerged with isosbestic
points at approximately 600 nm. The stoichiometries for the host-
guest complexes of 1a, 2a, and 3a with (R)-4 were determined
using Job plots (Figure 8d). The host-guest ratios of 1:1, 1:2, and
2.31(6) × 104
aEstimated based on standard errors given by the analysis.
Cooperativity in Guest Binding
The conformationally coupled multiple guest binding sites of a
multitopic host molecule often show cooperativity in their multiple
guest association.[30] At the molecular level, the cooperativity in
the multiple guest binding is described by the interaction
This article is protected by copyright. All rights reserved.

10.1002/chem.201800997
Chemistry - A European Journal
FULL PAPER
parameters α defined by the equations: α12 = 4K2/K1 and α12
=
therefore, the stereogenic centers of the amino acid groups
determined the left-handed helical sense of the host-guest
complex.
3K2/K1, α23 = 3K3/K2 for the 1:2 host-guest system and the 1:3
host-guest system, respectively. To evaluate the cooperative
effect in the multiple host-guest complexations of helicates 2a and
3a, the interaction parameters (α) for the multiple guest binding
were calculated (Table 3). The interaction parameters α12 and α23
of 2a and 3a are greater than unity, indicating that positive
cooperative effects are present in the encapsulation of the second
and the third guests. Therefore, the conformationally coupled two
or three binding sites sterically communicate with each other
through the tris(catecholato)iron(III) cores; that is, the first or
second guest binding information is effectively transferred, and
preorganizes the remaining binding sites. Then, the successive
guests are facilitated to become accessible for encapsulation into
the remaining cavities.
(a)
(b)
20
20
0
0
–20
–20
400
600
Wavelength / nm
400
600
Wavelength / nm
(c)
20
Table 3. Interaction parameter α of helicates 2a and 3a for (R)-4, (R)-5,
(R)-6, and 7.
0
2a
3a
Guests
α12
α12
α23
–20
(R)-4
(R)-5
(R)-6
7
4.5
5.7
6.9
3.5
3.5
6.5
3.4
2.4
1.7
3.4
9.0
13.7
400
600
Wavelength / nm
Figure 9. CD spectra of 1a (red), 2a (blue), and 3a (black) (a) with (R)-4 (solid
line) and (S)-4 (dashed line), (b) with (R)-5 (solid line) and (S)-5 (dashed line),
and (c) with (R)-6 (solid line) and (S)-6 (dashed line) in methanol at 298 K.
[Helicates] = 3.0 × 10–5 mol L–1 and [Guests] = 3.0 × 10–3 mol L–1
.
Chiral Induction
Helicates 1a, 2a, and 3a are D3-symmetric due to the lack of a
mirror plane. The (P)- and (M)-helical forms exist as racemic
Majority-rules Effect
Two chiral amplification mechanisms are possible in
supramolecular assemblies: the first is the sergeants-and-soldiers
principle, and the second is the majority-rules principle.[32] The
latter characterizes a non-linear response in chirality for the
assemblies consisting of both enantiomers of chiral monomers.
Small excess of one of the enantiomers results in a chiral
response in a non-linear fashion.[33],[34] The cooperativity of the
conformationally coupled guest binding cavities of 2a and 3a are
already established in the guest binding; therefore, majority rules
principle can be operative in the chiral guest recognition for 2a
and 3a. Figure 10a shows the CD spectra of 2a upon the variation
of the enantiomeric excess (ee) of 6. To confirm the cooperative
effect on the molecular recognition, the induced circular dichroism
(ICD) intensities at the LMCT bands versus the ee of guests 4–6
were plotted (Figures 10b,c,d). The complexation of 1a with chiral
guests 4–6 gave rise to the good linear correlation between the
ICD intensities and the ee of the guests. In contrast, the
complexation of the chiral guests 4–6 to the multiple guest binding
cavities of 2a and 3a showed a remarkable deviation from linearity,
indicating that the enantiomers in excess had a disproportionate
impact on the helicity of the metallohelicates.19 The deviation was
maximized when the guests were encapsulated within 3a over 2a,
suggesting that the cavities of 3a are more preorganized in a
helical manner than those of 2a. The majority-rules effects are
influenced by the steric bulkiness of the amino acid side chains.
The complexation of 4 to 2a and 3a showed smaller deviations
than the complexations of 5 and 6. Accordingly, the amino acid
mixtures
tris(catecholato)iron(III)
in
solution.
The
cores
labile
permits
nature
the
of
the
dynamic
interconversion between the (P)- and (M)-enantiomeric forms.
When a chiral guest is encapsulated, the chiral cavities recognize
the shape of the chiral guest, giving rise to an energy difference
between the diastereomeric complexes. Circular dichroism (CD)
spectroscopy was informative for gaining an insight into the
stereoselection of the diastereomeric complexes with the chiral
guests 4–6 (Figure 9). Induced CD emerged when the optically
active (R)- and (S)-4 were encapsulated within the cavities into
the solution of the metallohelicates (Figure 9a). The addition of
(R)-4 in the solutions of 1a resulted in the induced plus-to-minus
bisignate CD signals at 574 and at 446 nm, corresponding to the
LMCT band of the tris(catecholato)iron(III) core. The CD spectra
with (R)-4 and (S)-4 show a mirror-image relationship with respect
to the line of Δε = 0. The signal intensities at approximately 446
nm were dependent on the number of the guest binding cavities,
indicating that the chiral guest complexation within the
dissymmetric cavities resulted in an energy difference between
the (P)- and (M)-conformation and biased the population.
Raymond and co-workers reported that the absolute
stereochemistry of tris(catecholato)iron(III) was determined using
CD spectroscopy.[31] The plus-to-minus cotton effects at the
LMCT band correspond to the Λ-configuration of the metal cores
in the helicates possessing the (M)-conformation. (R)-5 and (R)-6
also induced the plus-to-minus cotton effects of 1a, 2a and 3a;
This article is protected by copyright. All rights reserved.

10.1002/chem.201800997
Chemistry - A European Journal
FULL PAPER
side chains most likely generate the steric interaction to the
stereogenic metal centers, determining the absolute helical sense
of the metallohelicates.
JSPS KAKENHI Grant Numbers JP15H00946 (Stimuli-
responsive Chemical Species), JP15H00752 (New Polymeric
Materials Based on Element-Blocks), JP17H05375 (Coordination
Asymmetry), and JP17H05159 (π-Figuration). We also
acknowledge the Futaba Electronics Memorial Foundation.
1.0
(b)
(a)
f
a
0
Keywords: helicate • supramolecular chemistry • allostery •
majority-rules effect • calixarene
–10
–20
[1] R. A. Hegstrom and D. K. Kondepudi, Sci. Am. 1990, 262, 108-115.
[2] A. Klug, Angew. Chem. Int. Ed. Engl. 1983, 22, 565-582.
0
0
100
400
600
ee / %
Wavelength / nm
[3] K. C. Holmes, D. Popp, W. Gebhard and W. Kabsch, Nature 1990, 347, 44-
49.
1.0
1.0
(d)
(c)
[4] J. D. Watson and F. H. C. Crick, Nature 1953, 171, 737-738.
[5] L. Pauling, R. B. Corey and H. R. Branson, Proc. Natl. Acad. Sci. USA 1951,
37, 205-211.
[6] a) M. Liu, L. Zhang and T. Wang, Chem. Rev. 2015, 115, 7304-7397; b) E.
Yashima, N. Ousaka, D. Taura, K. Shimomura, T. Ikai and K. Maeda,
Chem. Rev. 2016, 116, 13752-13990.
[7] a) J. M. Lehn, Supramolecular Chemistry: Concepts and Perspectives, VCH,
Weinheim, 1995, p; b) M. A. Mateos-Timoneda, M. Crego-Calama and
D. N. Reinhoudt, Chem. Soc. Rev. 2004, 33, 363-372; c) E. Yashima, K.
Maeda and Y. Furusho, Acc. Chem. Res. 2008, 41, 1166-1180; d) Q. Jin,
L. Zhang, H. Cao, T. Wang, X. Zhu, J. Jiang and M. Liu, Langmuir 2011,
27, 13847-13853; e) M. M. Safont-Sempere, G. Fernández and F.
Würthner, Chem. Rev. 2011, 111, 5784-5814; f) J. Kumar, T. Nakashima,
H. Tsumatori and T. Kawai, J. Phys. Chem. Lett. 2014, 5, 316-321.
[8] a) N. Kimizuka, T. Kawasaki, K. Hirata and T. Kunitake, J. Am. Chem. Soc.
1995, 117, 6360-6361; b) J. H. K. K. Hirschberg, L. Brunsveld, A. Ramzi,
J. A. J. M. Vekemans, R. P. Sijbesma and E. W. Meijer, Nature 2000,
407, 167-170; c) M. Reggelin, M. Schultz and M. Holbach, Angew. Chem.
Int. Ed. 2002, 41, 1614-1617; d) P. Jonkheijm, F. J. M. Hoeben, R.
Kleppinger, J. van Herrikhuyzen, A. P. H. J. Schenning and E. W. Meijer,
J. Am. Chem. Soc. 2003, 125, 15941-15949; e) M. M. J. Smulders, A. P.
H. J. Schenning and E. W. Meijer, J. Am. Chem. Soc. 2008, 130, 606-
611; f) T. Yamamoto and M. Suginome, Angew. Chem. Int. Ed. 2009, 48,
539-542; g) S. Yagai, H. Aonuma, Y. Kikkawa, S. Kubota, T. Karatsu, A.
Kitamura, S. Mahesh and A. Ajayaghosh, Chem. Eur. J. 2010, 16, 8652-
8661; h) F. Würthner, T. E. Kaiser and C. R. Saha-Möller, Angew. Chem.
Int. Ed. 2011, 50, 3376-3410; i) R. P. Megens and G. Roelfes, Chem.
Eur. J. 2011, 17, 8514-8523; j) P. A. Korevaar, S. J. George, A. J.
Markvoort, M. M. J. Smulders, P. A. J. Hilbers, A. P. H. J. Schenning, T.
F. A. De Greef and E. W. Meijer, Nature 2012, 481, 492-496; k) T. Miyabe,
H. Iida, A. Ohnishi and E. Yashima, Chem. Sci. 2012, 3, 863-867; l) S. I.
Stupp and L. C. Palmer, Chem. Mater. 2014, 26, 507-518; m) Y. Akai, L.
Konnert, T. Yamamoto and M. Suginome, Chem. Commun. 2015, 51,
7211-7214; n) H. Wang, N. Li, Z. Yan, J. Zhang and X. Wan, RSC Adv.
2015, 5, 2882-2890; o) Y. Yoshinaga, T. Yamamoto and M. Suginome,
ACS Macro Lett. 2017, 6, 705-710.
0
0
0
100
0
100
ee / %
ee / %
Figure 10. (a) CD spectra of 2a (1.0 × 10–4 mol L–1) in the presence of mixtures
[(S)-6]x + [(R)-6]1–x (1.0 × 10–2 mol L–1) (a–f: X = 0.5, 0.60, 0.70, 0.80, 0.90, 1.00)
in methanol at 298 K. (b)–(d) Plots of normalized ICD intensities at the LMCT
bands of 1a (red circle), 2a (blue circle), and 3a (black circle) versus ee of (b) 4,
(c) 5, and (d) 6. [Helicates] = 1.0 × 10–4 mol L–1 and [Guests] = 1.0 × 10–2 mol
L–1
.
Conclusions
In conclusion, we have demonstrated that the triple-stranded
metallohelicates can be developed through the self-organization
of the trivalent metal ions and the multidentate bridging ligands.
The multiple guest-binding cavities are conformationally coupled;
therefore, a first guest binding preorganizes the rest of the binding
cavities in the multiple cavities; as a result, large positive
cooperative effects are manifested in the guest binding. The chiral
guest complexation within the multiple guest-binding cavities
determines the helical sense of the metallohelicates, directed by
the stereogenic center of the amino acid. The chiral guest
complexation to the metallohelicates gives rise to the non-linear
relationships in the stereoselection for the helical direction, which
are the so-called majority-rules effects. Accordingly, the induced
chirality on a monomer unit is communicated to the other units
through the strands, modulating the internal spaces in such a way
that the second and the third guests are easily accessible for the
remaining cavities. These findings offer a facile synthetic strategy
for readily preparing optically active multiple-stranded
organizations with controlled helicity.
[9] a) D. M. Bassani, J.-M. Lehn, G. Baum and D. Fenske, Angew. Chem. Int.
Ed. Engl. 1997, 36, 1845-1847; b) O. Mamula, A. von Zelewsky, T. Bark
and G. Bernardinelli, Angew. Chem. Int. Ed. 1999, 38, 2945-2948; c) V.
Berl, I. Huc, R. G. Khoury and J.-M. Lehn, Chem. Eur. J. 2001, 7, 2810-
2820; d) X.-M. Chen and G.-F. Liu, Chem. Eur. J. 2002, 8, 4811-4817; e)
Y. Tanaka, H. Katagiri, Y. Furusho and E. Yashima, Angew. Chem. Int.
Ed. 2005, 44, 3867-3870; f) H. Goto, H. Katagiri, Y. Furusho and E.
Yashima, J. Am. Chem. Soc. 2006, 128, 7176-7178; g) D. Haldar and C.
Schmuck, Chem. Soc. Rev. 2009, 38, 363-371; h) S. Li, C. Jia, B. Wu,
Q. Luo, X. Huang, Z. Yang, Q.-S. Li and X.-J. Yang, Angew. Chem. Int.
Ed. 2011, 50, 5721-5724; i) B. Wu, S. Li, Y. Lei, H. Hu, N. de Sousa
Amadeu, C. Janiak, J. S. Mathieson, D.-L. Long, L. Cronin and X.-J.
Yang, Chem. Eur. J. 2015, 21, 2588-2593; j) C. Jia, W. Zuo, D. Yang, Y.
Acknowledgements
This work was supported by Grants-in-Aid for Scientific Research,
JSPS KAKENHI Grant Numbers JP15H03817 and JP15KT0145,
and by Grants-in-Aid for Scientific Research on Innovative Areas,
This article is protected by copyright. All rights reserved.

10.1002/chem.201800997
Chemistry - A European Journal
FULL PAPER
Chen, L. Cao, R. Custelcean, J. Hostaš, P. Hobza, R. Glaser, Y.-Y. Wang,
X.-J. Yang and B. Wu, Nat. Commun. 2017, 8.
7545; c) F. Cui, S. Li, C. Jia, J. S. Mathieson, L. Cronin, X.-J. Yang and
B. Wu, Inorg. Chem. 2012, 51, 179-187; d) U. Kiehne, T. Weilandt and
A. Lützen, Org. Lett. 2007, 9, 1283-1286; e) C. J. Baylies, T. Riis-
Johannessen, L. P. Harding, J. C. Jeffery, R. Moon, C. R. Rice and M.
Whitehead, Angew. Chem. Int. Ed. 2005, 44, 6909-6912; f) A. Lützen, M.
Hapke, J. Griep-Raming, D. Haase and W. Saak, Angew. Chem. Int. Ed.
2002, 41, 2086-2089; g) M. Greenwald, D. Wessely, E. Katz, I. Willner
and Y. Cohen, J. Org. Chem. 2000, 65, 1050-1058; h) N. Fatin-Rouge,
S. Blanc, E. Leize, A. Van Dorsselaer, P. Baret, J.-L. Pierre and A.-M.
Albrecht-Gary, Inorg. Chem. 2000, 39, 5771-5778; i) M. Greenwald, D.
Wessely, I. Goldberg and Y. Cohen, New J. Chem. 1999, 23, 337-344; j)
J. J. Jodry and J. Lacour, Chem. Eur. J. 2000, 6, 4297-4304; k) G. Baum,
E. C. Constable, D. Fenske and T. Kulke, Chem. Commun. 1997, 2043-
2044.
[10] a) J.-M. Lehn, A. Rigault, J. Siegel, J. Harrowfield, B. Chevrier and D. Moras,
Proc. Natl. Acad. Sci. USA 1987, 84, 2565-2569; b) A. Pfeil and J.-M.
Lehn, J. Chem. Soc., Chem. Commun. 1992, 838-840; c) B. Hasenknopf,
J.-M. Lehn, G. Baum and D. Fenske, Proc. Natl. Acad. Sci. USA 1996,
93, 1397-1400; d) A. Marquis-Rigault, A. Dupont-Gervais, A. Van
Dorsselaer and J.-M. Lehn, Chem. Eur. J. 1996, 2, 1395-1398; e) V. C.
M. Smith and J.-M. Lehn, Chem. Commun. 1996, 2733-2734; f) A.
Marquis, V. Smith, J. Harrowfield, J.-M. Lehn, H. Herschbach, R. Sanvito,
E. Leize-Wagner and A. Van Dorsselaer, Chem. Eur. J. 2006, 12, 5632-
5641.
[11] a) C. A. Schalley, A. Lützen and M. Albrecht, Chem. Eur. J. 2004, 10, 1072-
1080; b) C. R. K. Glasson, L. F. Lindoy and G. V. Meehan, Coord. Chem.
Rev. 2008, 252, 940-963; c) S. E. Howson and P. Scott, Dalton Trans.
2011, 40, 10268-10277; d) M. Albrecht, Chem. Rev. 2001, 101, 3457-
3497.
[19] a) S.-Y. Chang, H.-Y. Jang and K.-S. Jeong, Chem. Eur. J. 2004, 10, 4358-
4366; b) S. Freye, J. Hey, A. Torras-Galán, D. Stalke, R. Herbst-Irmer,
M. John and G. H. Clever, Angew. Chem. Int. Ed. 2012, 51, 2191-2194;
c) O. Gidron, M. Jirásek, M. Wörle and F. Diederich, Chem. Eur. J. 2016,
22, 16172-16177; d) W. J. Ramsay, T. K. Ronson, J. K. Clegg and J. R.
Nitschke, Angew. Chem. Int. Ed. 2013, 52, 13439-13443.
[12] a) E. C. Constable and R. Chotalia, J. Chem. Soc., Chem. Commun. 1992,
64-66; b) C. Provent, S. Hewage, G. Brand, G. Bernardinelli, L. J.
Charbonnière and A. F. Williams, Angew. Chem. Int. Ed. Engl. 1997, 36,
1287-1289; c) D. A. McMorran and P. J. Steel, Angew. Chem. Int. Ed.
1998, 37, 3295-3297; d) C. R. Rice, S. Wörl, J. C. Jeffery, R. L. Paul and
M. D. Ward, Chem. Commun. 2000, 1529-1530; e) P. K. Bowyer, V. C.
Cook, N. Gharib-Naseri, P. A. Gugger, A. D. Rae, G. F. Swiegers, A. C.
Willis, J. Zank and S. B. Wild, Proc. Natl. Acad. Sci. USA 2002, 99, 4877-
4882; f) V. Maurizot, G. Linti and I. Huc, Chem. Commun. 2004, 924-925;
g) M. Bera, G. Aromí, W. T. Wong and D. Ray, Chem. Commun. 2006,
671-673; h) W. Chen, X. Tang, W. Dou, B. Wang, L. Guo, Z. Ju and W.
Liu, Chem. Eur. J. 2017, 23, 9804-9811; i) S. Naskar, C. Dalal and P.
Ghosh, Chem. Commun. 2017, 53, 2487-2490; j) E. C. Constable, T.
Kulke, M. Neuburger and M. Zehnder, Chem. Commun. 1997, 489-490;
k) J. S. Fleming, K. L. V. Mann, S. M. Couchman, J. C. Jeffery, J. A.
McCleverty and M. D. Ward, J. Chem. Soc., Dalton Trans. 1998, 2047-
2052; l) V. Amendola, L. Fabbrizzi, L. Gianelli, C. Maggi, C. Mangano, P.
Pallavicini and M. Zema, Inorg. Chem. 2001, 40, 3579-3587; m) R.
Annunziata, M. Benaglia, A. Famulari and L. Raimondi, Magn. Reson.
Chem. 2001, 39, 341-354; n) W. Schuh, H. Kopacka, K. Wurst and P.
Peringer, Chem. Commun. 2001, 2186-2187.
[20] T. Haino, H. Shio, R. Takano and Y. Fukazawa, Chem. Commun. 2009,
2481-2483.
[21] A. M. A. van Wageningen, E. Snip, W. Verboom, D. N. Reinhoudt and H.
Boerrigter, Liebigs Ann. Recl. 1997, 2235-2245.
[22] a) S. Salama, J. D. Stong, J. B. Neilands and T. G. Spiro, Biochemistry
1978, 17, 3781-3785; b) T. B. Karpishin, M. S. Gebhard, E. I. Solomon
and K. N. Raymond, J. Am. Chem. Soc. 1991, 113, 2977-2984.
[23] a) Y. Cohen, L. Avram and L. Frish, Angew. Chem. Int. Ed. 2005, 44, 520-
554; b) A. S. Altieri, D. P. Hinton and R. A. Byrd, J. Am. Chem. Soc. 1995,
117, 7566-7567.
[24] a) L. Avram and Y. Cohen, Chem. Soc. Rev. 2015, 44, 586-602; b) A.
Macchioni, G. Ciancaleoni, C. Zuccaccia and D. Zuccaccia, Chem. Soc.
Rev. 2008, 37, 479-489.
[25] a) N. Dalla Favera, L. Guenee, G. Bernardinelli and C. Piguet, Dalton Trans.
2009, 7625-7638; b) B. M. Schulze, D. L. Watkins, J. Zhang, I. Ghiviriga
and R. K. Castellano, Org. Biomol. Chem. 2014, 12, 7932-7936.
[26] a) F. Mohamadi, N. G. J. Richards, W. C. Guida, R. Liskamp, M. Lipton, C.
Caufield, G. Chang, T. Hendrickson and W. C. Still, J. Comput. Chem.
1990, 11, 440-467; b) S. J. Weiner, P. A. Kollman, D. A. Case, U. C.
Singh, C. Ghio, G. Alagona, S. Profeta, Jr. and P. Weiner, J. Am. Chem.
Soc. 1984, 106, 765-784.
[13] a) B. Kersting, M. Meyer, R. E. Powers and K. N. Raymond, J. Am. Chem.
Soc. 1996, 118, 7221-7222; b) B. Kersting, J. R. Telford, M. Meyer and
K. N. Raymond, J. Am. Chem. Soc. 1996, 118, 5712-5721; c) D. L.
Caulder and K. N. Raymond, Angew. Chem. Int. Ed. Engl. 1997, 36,
1440-1442; d) M. Meyer, B. Kersting, R. E. Powers and K. N. Raymond,
Inorg. Chem. 1997, 36, 5179-5191.
[27] a) M. Albrecht, S. Mirtschin, M. de Groot, I. Janser, J. Runsink, G. Raabe,
M. Kogej, C. A. Schalley and R. Fröhlich, J. Am. Chem. Soc. 2005, 127,
10371-10387; b) A. Marquis-Rigault, A. Dupont-Gervais, P. N. W. Baxter,
A. Van Dorsselaer and J.-M. Lehn, Inorg. Chem. 1996, 35, 2307-2310.
[28] I. Kolossváry and W. C. Guida, J. Am. Chem. Soc. 1996, 118, 5011-5019.
[29] a) A. Braibanti, G. Ostacoli, P. Paoletti, L. D. Pettit and S. Sammartano,
Pure Appl. Chem. 1987, 59, 1721-1728; b) K. A. Connors, Binding
Constants: The Measurements of Molecular Complex Stability, John
Wiley & Sons, New York, 1987, p; c) P. Gans, A. Sabatini and A. Vacca,
Talanta 1996, 43, 1739-1753; d) P. Gans, A. Sabatini and A. Vacca, Ann.
Chim. 1999, 89, 45-49.
[14] E. J. Enemark and T. D. P. Stack, Angew. Chem. Int. Ed. Engl. 1995, 34,
996-998.
[15] a) M. Albrecht and S. Kotila, Angew. Chem. Int. Ed. Engl. 1995, 34, 2134-
2137; b) I. Janser, M. Albrecht, K. Hunger, S. Burk and K. Rissanen, Eur.
J. Inorg. Chem. 2006, 244-251; c) M. Albrecht, E. Isaak, H. Shigemitsu,
V. Moha, G. Raabe and R. Fröhlich, Dalton Trans. 2014, 43, 14636-
14643; d) D. Van Craen, M. Albrecht, G. Raabe, F. Pan and K. Rissanen,
Chem. Eur. J. 2016, 22, 3255-3258.
[16] a) H. V. Huynh, C. Schulze Isfort, W. W. Seidel, T. Lügger, R. Fröhlich, O.
Kataeva and F. E. Hahn, Chem. Eur. J. 2002, 8, 1327-1335; b) F. E.
Hahn, C. Schulze Isfort and T. Pape, Angew. Chem. Int. Ed. 2004, 43,
4807-4810; c) C. Schulze Isfort, T. Kreickmann, T. Pape, R. Fröhlich and
F. E. Hahn, Chem. Eur. J. 2007, 13, 2344-2357; d) F. E. Hahn, M.
Offermann, C. Schulze Isfort, T. Pape and R. Fröhlich, Angew. Chem.
Int. Ed. 2008, 47, 6794-6797.
[30] a) H. J. Hogben, J. K. Sprafke, M. Hoffmann, M. Pawlicki and H. L.
Anderson, J. Am. Chem. Soc. 2011, 133, 20962-20969; b) C.-H. Lee, H.
Yoon, P. Kim, S. Cho, D. Kim and W.-D. Jang, Chem. Commun. 2011,
47, 4246-4248; c) J. Wang, D.-T. Pham, T. W. Kee, S. N. Clafton, X. Guo,
P. Clements, S. F. Lincoln, R. K. Prud'homme and C. J. Easton,
Macromolecules 2011, 44, 9782-9791; d) S. Brahma, S. A. Ikbal, A.
Dhamija and S. P. Rath, Inorg. Chem. 2014, 53, 2381-2395; e) D.
Shimoyama, H. Yamada, T. Ikeda, R. Sekiya and T. Haino, Eur. J. Org.
Chem. 2016, 3300-3303; f) P. Mondal, S. Sarkar and S. P. Rath, Chem.
Eur. J. 2017, 23, 7093-7103; g) L. K. S. von Krbek, A. J. Achazi, S.
Schoder, M. Gaedke, T. Biberger, B. Paulus and C. A. Schalley, Chem.
Eur. J. 2017, 23, 2877-2883; h) Y.-L. Ma, H. Ke, A. Valkonen, K.
Rissanen and W. Jiang, Angew. Chem. Int. Ed. 2018, 57, 709-713.
[17] a) R. M. Yeh, M. Ziegler, D. W. Johnson, A. J. Terpin and K. N. Raymond,
Inorg. Chem. 2001, 40, 2216-2217; b) R. M. Yeh and K. N. Raymond,
Inorg. Chem. 2006, 45, 1130-1139.
[18] a) D. Zare, Y. Suffren, H. Nozary, A. Hauser and C. Piguet, Angew. Chem.
Int. Ed. 2017, 56, 14612-14617; b) J. L. Greenfield, F. J. Rizzuto, I.
Goldberga and J. R. Nitschke, Angew. Chem. Int. Ed. 2017, 56, 7541-
This article is protected by copyright. All rights reserved.

10.1002/chem.201800997
Chemistry - A European Journal
FULL PAPER
[31] T. B. Karpishin, T. D. P. Stack and K. N. Raymond, J. Am. Chem. Soc. 1993,
115, 6115-6125.
J. Am. Chem. Soc. 2003, 125, 1278-1283; c) B. Isare, M. Linares, L.
Zargarian, S. Fermandjian, M. Miura, S. Motohashi, N. Vanthuyne, R.
Lazzaroni and L. Bouteiller, Chem. Eur. J. 2010, 16, 173-177; d) M. M. J.
Smulders, I. A. W. Filot, J. M. A. Leenders, P. van der Schoot, A. R. A.
Palmans, A. P. H. J. Schenning and E. W. Meijer, J. Am. Chem. Soc.
2010, 132, 611-619; e) T. Kim, T. Mori, T. Aida and D. Miyajima, Chem.
Sci. 2016, 7, 6689-6694; f) Y. Tsunoda, M. Takatsuka, R. Sekiya and T.
Haino, Angew. Chem. Int. Ed. 2017, 56, 2613-2618.
[32] a) J. van Gestel, Macromolecules 2004, 37, 3894-3898; b) J. van Gestel, J.
Phys. Chem. B 2006, 110, 4365-4370.
[33] a) M. M. Green, J.-W. Park, T. Sato, A. Teramoto, S. Lifson, R. L. B.
Selinger and J. V. Selinger, Angew. Chem. Int. Ed. 1999, 38, 3138-3154;
b) A. R. A. Palmans and E. W. Meijer, Angew. Chem. Int. Ed. 2007, 46,
8948-8968.
[34] a) M. M. Green, N. C. Peterson, T. Sato, A. Teramoto, R. Cook and S.
Lifson, Science 1995, 268, 1860-1866; b) R. Nonokawa and E. Yashima,
This article is protected by copyright. All rights reserved.

10.1002/chem.201800997
Chemistry - A European Journal
FULL PAPER
Entry for the Table of Contents (Please choose one layout)
FULL PAPER
Triple helices: Calix[4]arene-based
triple-stranded metallohelicates
encapsulate cationic guests within
the binding cavities, which are
Yutaro Yamasaki, Hidemi Shio,
Tomoko Amimoto, Ryo Sekiya and
Takeharu Haino*
Page No. – Page No.
conformationally coupled. Their
cooperative guest binding directs the
allosteric effect and majority-rules
effect in the molecular recognition.
Majority-Rules Effect and Allostery
in Molecular Recognition of
Calix[4]arene-Based Triple-Stranded
Metallohelicates
This article is protected by copyright. All rights reserved.