Copper(ii)-mediated chiral helicity amplification and inversion of meta-ethynylpyridine polymers with metal coordination sites

Article abstract of DOI:10.1039/c1cc12358k

meta-Ethynylpyridine polymers bearing metal coordination sites associate with alkyl glycoside guests to show induced circular dichroism (ICD) bands. The addition of a Cu(ii) ion changed the intensity or the sign of these ICD bands. The changes suggested chiral helicity amplification or inversion of the polymers by Cu(ii)-mediated cross-linking at the coordinating side chains.

Full text of DOI:10.1039/c1cc12358k

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COMMUNICATION
Copper(II)-mediated chiral helicity amplification and inversion of
meta-ethynylpyridine polymers with metal coordination sitesw
Shunsuke Takashima, Hajime Abe* and Masahiko Inouye*
Received 22nd April 2011, Accepted 17th May 2011
DOI: 10.1039/c1cc12358k
meta-Ethynylpyridine polymers bearing metal coordination sites
associate with alkyl glycoside guests to show induced circular
dichroism (ICD) bands. The addition of a Cu(II) ion changed the
intensity or the sign of these ICD bands. The changes suggested
chiral helicity amplification or inversion of the polymers by
Cu(II)-mediated cross-linking at the coordinating side chains.
Helical structures in biopolymers play crucial roles in living
systems both for constructing their own higher-order structures
and interacting with others.1 Among them, helices of DNA
and peptides are often stabilized by the presence of chemical
species with small molecular weights such as metal ions.1b,c
Fig. 1 meta-Ethynylpyridine polymers 1–4.
Metal ion-mediated higher-order architectures also have been
structure between the azacrown and the oligoammonium
seen in synthetic molecules.2,3 Lehn et al. developed double-
moieties, which stabilized the chiral helical complexes by
stranded helicates by spontaneous assembly of oligobipyridine
cross-linking the side chains. Herein, we report a new type
ligands and metal ions.3a Yashima et al. reported the control
of meta-ethynylpyridine polymers 2–4 with metal-coordination
of the spring-like motion of double-stranded helicates by the
sites (bis(2-methoxyethyl)amino groups) attached through
addition and removal of sodium ions.3h
mono-, di-, and tri-oxyethylene spacers at the 4-position of
Our group has developed 2,6-pyridylene ethynylene ‘‘meta-
each pyridine unit, respectively (Fig. 1). The coordination of
ethynylpyridine’’ polymers and oligomers, which consisted of
metal ions would be expected to stabilize (or destabilize) the
4-functionalized pyridine rings linked at their 2,6-positions
helical structure by cross-linking the side chains much straight-
with acetylene bonds.4 These polymers and oligomers recognize
forwardly than the pseudopolyrotaxane formation in 1 (Fig. 2).
various kinds of saccharide guests by multiple hydrogen bonds
The polymer 2 was prepared as shown in Scheme 1.
between pyridine nitrogen atoms and hydroxy groups of the
guests.5–7 The resulting complexes form biased helical structures
to show circular dichroisms (CDs).8 Functional groups at the
Commercially available 2,6-dibromopyridine was converted
into 2,6-dibromo-4-nitropyridine (5) in three steps.9 Aromatic
substitution on
5 with monosodium ethylene glycolate
4-positions on the pyridine units build on extra characteristics
such as amphiphilicity4c,d and strong basicity4b to the polymers
and oligomers. Recently, we reported an azacrown-attached
meta-ethynylpyridine polymer 1 that incorporates additional
molecular recognition sites at its side chains4g (Fig. 1). When
octyl b-D- and L-glucopyranosides were added to a CH2Cl2
solution of 1, a mirror-image pair of induced CD (ICD) bands
was observed, indicating that 1 formed chiral helical complexes
with the guests. These ICDs were significantly enhanced by the
addition of oligoammonium cations. The ICD enhancements
would be due to the formation of a pseudopolyrotaxane
(ethylene glycol and sodium hydride) gave 2,6-dibromo-4-(2-
hydroxyethyloxy)pyridine (6). After halogen exchange of 6
into diiodide 7,10 the hydroxy group was tosylated to give 8.
Then, a Cu(II)-coordination site was introduced to 8 by the
condensation with bis(2-methoxyethyl)amine to afford tertiary
amine 9. Diacetylene 11 was obtained from 9 by the Sonogashira
reaction with trimethylsilylacetylene followed by protiodesilylation.
The final co-polymerization between the diiodide 9 and the
Graduate School of Pharmaceutical Sciences, University of Toyama,
Sugitani 2630, Toyama 930-0194, Japan. E-mail: abeh@pha.u-
toyama.ac.jp; Fax: +81 76-434-5049
w Electronic supplementary information (ESI) available: Detailed
synthetic procedures for 2–4, Fig. S1–S5. The corresponding UV
changes are shown in Fig. S6–S10. See DOI: 10.1039/c1cc12358k
Fig. 2 Schematic diagram of helix stabilization of meta-ethynylpyridine
host polymers by coordination of metal ions at the side chains.
c
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Fig. 3 The additive effect of Cu(II) triflate and ethylenediamine
(EDA) on the ICDs of host polymer
2 associated with octyl
b-glucopyranosides (b-D-Glc and b-L-Glc). Blue solid: 2; red solid:
2 + b-D-Glc; green solid: 2 + b-D-Glc + Cu(OTf)2; purple solid: 2 +
b-D-Glc + Cu(OTf)2 + EDA; red broken: 2 + b-L-Glc; green broken:
2 + b-L-Glc + Cu(OTf)2. Conditions: 2 (1.0 Â 10À3 M, unit conc.),
b-Glc (2.0 Â 10À3 M), Cu(OTf)2 (5.0 Â 10À4 M), EDA (5.0 Â 10À4 M),
CH2Cl2, 25 1C, path length = 1 mm. Cu(OTf)2 was added as a DMSO
solution of a 1/300 amount to the sample solution.
Scheme 1 Preparation of host polymer 2. TMSA = trimethylsilyl-
acetylene, TBAF = tetrabutylammonium fluoride.
diacetylene 11 was carried out by the Sonogashira reaction to
yield the polymeric product 2 as a brown oil. After the
treatment with a short Sephadex LH-20 column, the product
was subjected to gel permeation chromatography (GPC), and
one fraction of Mn = 12 700 g molÀ1 (vs. polystyrene (PS)
standards) was applied to the following experiments. The
polymers 3 and 4, in which Cu(II)-coordination sites are
attached through longer spacers than that of 2, were prepared
by similar procedures by using diethylene glycol and triethylene
glycol instead of ethylene glycol, respectively (see ESIw). After
GPC separation, each fraction of 3 (Mn = 12 500 g molÀ1 vs.
PS standards) and 4 (Mn = 16 200 g molÀ1 vs. PS standards)
was used. These Mn values for the fractions of 2, 3, and 4
correspond to ca. 46-, 39-, and 45-meric pyridylene ethynylene
polymers, respectively.
glucoside guests was found to be transferred to the helical
sense of the polymer.
Other kinds of glycoside guests were also investigated under
the same conditions. When applying b-D-Fru and b-D-Man to
2, positive ICD bands appeared around 338 nm and 337 nm,
respectively (red solid lines in Fig. 4A and B), almost similar
to those of our previous butyloxy-substituted meta-ethynyl-
pyridine polymers.4a However, after addition of Cu(II) triflate
to the mixture of 2 and b-D-Fru, the sign of the ICD inverted
and the absolute value largely increased (Fig. 4A, green solid
line). On the other hand, slight decrease of the ICD was
observed after the addition in the case of b-D-Man (Fig. 4B,
green solid line). These transformations of the CD spectra
upon the addition of a Cu(II) ion proceeded in different
manners as in b-D-Glc. The Cu(II) ion stabilized the helical
complex between 2 and b-D-Fru in an inverse manner of the
chirality, while the complex of b-D-Man was scarcely affected.
Indeed, ethylenediamine canceled the Cu(II) effect for b-D-Fru
and had little influence on that for b-D-Man.
Saccharide recognition ability and additive effects of a Cu(II)
ion were studied on the basis of CD spectra. The applied
glycoside guests in this study were octyl b-D-glucopyranoside
(b-D-Glc), octyl b-L-glucopyranoside (b-L-Glc), octyl b-D-
fructopyranoside (b-D-Fru), and octyl b-D-mannopyranoside
(b-D-Man) (Fig. S1 in ESIw). When b-D-Glc was added to a
CH2Cl2 solution of 2 (1.0 mM, unit conc.), a negative ICD
band appeared around CDmax = 336 nm (Fig. 3, red solid
line).11 This observation is indicative of the formation of the
helical complex between 2 and b-D-Glc. The shape of the ICD
was similar to those observed in the cases of other kinds of
meta-ethynylpyridine polymers associated with b-D-Glc.4
When Cu(II) triflate (0.5 mM, 0.5 eq. to pyridine units of 2)
was added to this mixture, the ICD was remarkably enhanced
and CDmax slightly shifted to 343 nm (Fig. 3, green solid line).
Subsequent addition of ethylenediamine (0.5 mM) in order to
capture the Cu(II) ion weakened the ICD near to silent (Fig. 3,
purple solid line).12 These transformations of the ICD suggest
that the chiral helical structure of the complex of 2 with
b-D-Glc would be stabilized by the addition of a Cu(II) ion,
and then destabilized by the addition of ethylenediamine. The
reason for the destabilization may be that ethylenediamines
can behave as not only Cu(II) chelating reagents but also
competitive guest molecules to 2. The opposite enantiomer
guest b-L-Glc was subjected to the same experiments and
induced a mirror-image ICD corresponding to that in the case
of b-D-Glc (Fig. 3, broken lines). Thus, the chirality of the
Fig. 4 The additive effect of Cu(II) triflate and ethylenediamine
(EDA) on the ICDs of host polymer 2 associated with (A) octyl
b-D-fructopyranoside (b-D-Fru) and (B) octyl b-D-mannopyranoside
(b-D-Man). Blue: 2; red: 2 + glycoside; green: 2 + glycoside +
Cu(OTf)2; purple: 2 + glycoside + Cu(OTf)2 + EDA. Conditions:
2 (1.0 Â 10À3 M, unit conc.), glycoside (2.0 Â 10À3 M), Cu(OTf)2
(5.0 Â 10À4 M), EDA (5.0 Â 10À4 M), CH2Cl2, 25 1C, path length = 1 mm.
Cu(OTf)2 was added as a DMSO solution of a 1/300 amount to the
sample solution.
c
7456 Chem. Commun., 2011, 47, 7455–7457
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The distance between the coordination sites and the pyridine
main chains proved to be important for the Cu(II)-regulated
helical transformations by using 3 and 4 as a host polymer.
Upon the addition of b-D-Glc to CH2Cl2 solutions of 3 and 4,
negative ICD bands were induced around 338 nm in both cases
as well as in 2 (red solid lines in Fig. S2A and S2B, ESIw).
However, unlike 2, the addition of Cu(II) triflate decreased
those ICDs (green solid lines in Fig. S2A and S2B, ESIw).
Similar CD-decreasing effects with Cu(II) were also observed
when b-D-Fru and b-D-Man were used as a guest (Fig. S3 and S4,
ESIw). These observations might mean the increased freedom of
the longer coordination sites, forming Cu(II) chelation with any
of other sites. After those, the treatment with ethylenediamine
to the mixture almost quenched the ICDs (Fig. S2–S4, ESIw).
The additive effects of the Cu(II) ion should also be ruminated
from a different point of view. In the host polymers, the amino
groups of the side chains and the pyridine nitrogens in the
main chain can coordinate with the Cu(II) ion. In the guest
glycosides, 1,2- and 1,3-diol structures can do as well.7 The
Cu(II)-induced ICD enhancement in b-D-Glc would reflect the
stabilization of the chiral helical complex as mentioned above.
This stabilization is likely to be rationalized by the following
two possibilities of outside and inside coordinations: (i) one
Cu(II) ion may link the two side chains outside the helix; (ii)
one Cu(II) ion may link the one or two pyridine nitrogens
inside the helix and one diol group of the incorporated guest
glycosides. Generally, the order of coordination affinity to the
Cu(II) ion will be in the following order: ethylenediamine 4
bis(2-methoxyethyl)amine group 4 pyridine ring 4 diol.13
Therefore, the possibility of (i) may be plausible, and the
chirality of the stabilized helix would be induced by the
glycoside guest which is hydrogen-bonded inside the helix.
The coordinating ability of the side chains was supported by
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4 (a) M. Inouye, M. Waki and H. Abe, J. Am. Chem. Soc., 2004, 126,
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and Z.-T. Li, J. Am. Chem. Soc., 2004, 126, 12386–12394;
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Tetrahedron, 2001, 57, 2349–2354; (b) S. Striegler and E. Tewes,
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1
an H NMR experiment using 9 and Cu(OTf)2 (see Fig. S5,
ESIw). In the case of b-D-Fru, the Cu(II)-stabilized helix was
inversely biased, compared to the helix without the Cu(II)
coordinations (Fig. 4A).
In summary, we have prepared meta-ethynylpyridine polymers
that possess Cu(II)-coordination sites at each pyridine unit.
These polymers associate with saccharide guests and form
biased helical complexes to show characteristic ICDs. The
ICDs were enhanced, decreased, or inverted by the addition of
a Cu(II) ion to the complex of polymer and saccharide,
suggesting that the helical complex was stabilized or destabilized
by cross-linking the side chains with the Cu(II) ion.
Notes and references
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2 Reviews for conformational controls of supramolecular structures
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11 See also Fig. S11 in ESIw for the titration curve.
12 When the addition order of b-D-Glc and Cu(II) ion was reversed, a
small ICD band was retained even after reaching equilibrium in
four hours upon the addition of b-D-Glc. The ICD was five times
smaller than that shown in Fig. 3. When Cu(OTf)2 was added to 2
before the addition of saccharide, cross-linking occurred at the side
chains of 2 that exists in a manner of its random structure.
Subsequent addition of the saccharide seems to be difficult to
transform the random structure into a helical one. See Fig. S12
in the ESIw.
3 For examples of synthetic helices involving metal ion;
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13 S. R. Cooper, Crown Compounds Toward Future Applications,
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c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 7455–7457 7457