J. Am. Chem. Soc. 2001, 123, 7441-7442
7441
A Helical Polyelectrolyte Induced by Specific
Interactions with Biomolecules in Water
Hisanari Onouchi,† Katsuhiro Maeda,† and Eiji Yashima*,†,‡
Department of Molecular Design and Engineering
Graduate School of Engineering, Nagoya UniVersity
Nagoya 464-8603, Japan
Form and Function, PRESTO, JST, Chikusa-ku
Nagoya 464-8603, Japan
ReceiVed April 22, 2001
ReVised Manuscript ReceiVed June 11, 2001
Figure 1. Schematic illustration of right- and left-handed helicity
induction in achiral poly-1 upon complexation with chiral biomolecules.
Nucleic acids are typical polyelectrolytes with a phosphate
backbone and bind to proteins and a variety of oppositely charged
biomolecules and drugs in aqueous solution where electrostatic
interactions and/or directed hydrogen bonding play a central role.1
Polyelectrolytes are completely different from small electrolytes;
that is, a portion of the counterions are bound to polyelectrolytes
of a sufficiently high charge density, so that polyelectrolytes can
efficiently interact with small charged molecules in water.2 In
sharp contrast, small electrolytes exhibit only the dissociated free
ions in water by hydration, therefore, the rationale design of
charged synthetic receptors for biomolecular recognition in water
still remains a very difficult problem to solve.3
Figure 2. Possible interaction models of peptides (A), 1,3-amino alcohols
(B),8 and 1,2-diols (C)9 with the phosphodiester backbone of the nucleic
acids.1
We previously reported the induction of helicity in an achiral,
stereoregular poly((4-carboxyphenyl)acetylene) with chiral amines
in dimethyl sulfoxide (DMSO)4 and some amino acids in water.5
The complexes showed an induced circular dichroism (ICD) in
the UV-visible region due to the predominantly one-handed helix
formation. However, the polymer is not sensitive to amino acids
and other important chiral biomolecules in the fields of biology
and medicine. Here we show that a rationally designed polyelec-
trolyte, cis-transoidal poly((4-phosphonophenyl)acetylene) (poly-
1; Figure 1),6 bioinspired by the interaction motifs of nucleic acids
(Figure 2), interacts with a variety of biomolecules and forms
supramolecular assemblies with controlled helicity through elec-
trostatic and hydrogen bonding interactions in water. Phosphodi-
esters of nucleic acids are proposed to bind the backbone of the
polypeptide main chain as well as the terminal and side chain
basic amino groups (A),1,7 the 1,2- or 1,3-amino alcohol residues
(B),1b-d,8 and the 1,2-diols (C).9 If these interactions would occur
in water, we could detect and evaluate their specific interactions
without derivatization using CD spectroscopy with poly-1 as a
sensitive probe.
Figure 3A shows the typical CD and absorption spectra of
poly-1 in the presence of a free amino acid, D-tryptophan, and
L-tryptophan (Trp) in water at 25 °C. The complexes showed
mirror images of the split-type ICDs. The assay of 19 of the
common free L-amino acids produced ICDs with the sign
reflecting the absolute configurations; thirteen neutral and two
acidic L-amino acids gave the same ICD signs, while the
secondary amino acid, L-proline, and the three basic amino acids,
L-arginine, L-histidine, and L-lysine, gave the opposite ICD sign
(negative second Cotton) as expected (see Supporting Informa-
tion).10 The magnitude of the ICD was influenced by the pH and
the salt (NaCl) concentration because the phosphono group of
poly-1 has two acidic OH groups with different pKa values (ca.
1.8 and 7.1), which is consistent with the ionic nature of the
interaction. This is the first example of chirality assignments of
all the common free L-amino acids in water.11
† Nagoya University.
As expected, poly-1 also complexes with the terminal amino
group of the peptides and exhibits an ICD in water at 25 °C. It
is worth noting that poly-1 showed ICDs in the presence of Gly-
L-Ala (the molar ellipticities of the second Cotton (∆ꢀsecond) of
poly-1 ) 9.0 (M-1cm-1)) and Gly-Gly-L-Ala (∆ꢀsecond ) 8.3) at
pH 5.0 with remote stereogenic centers from the terminal amino
‡ PRESTO, JST.
(1) (a) Saenger, W. Principles of Nucleic Acid Structure; Springer-Verlag:
New York, 1984; Chapter 18. (b) Patel, J. D.; Suri, A. K.; Jiang, F.; Jiang,
L.; Fan, P.; Kumar, R. A.; Nonin, S. J. Mol. Biol. 1997, 272, 645-664. (c)
Chow, C. C.; Bogdan, F. M. Chem. ReV. 1997, 97, 1489-1513. (d) Hermann,
T. Angew. Chem., Int. Ed. 2000, 39, 1890-1905.
(2) (a) Manning, G. S. Acc. Chem. Res. 1979, 12, 443-449. (b) Molecular
Conformation and Dynamics of Macromolecules in Condensed System;
Nagasawa, M., Ed.; Elsevier: New York, 1988.
(9) (a) Das, G.; Hamilton, A. D. J. Am. Chem. Soc. 1994, 116, 11139-
11140. (b) Pelmore, H.; Eaton, G.; Symons, M. C. R. J. Chem. Soc., Perkin
Trans. 2 1992, 149-150.
(3) For recent examples of chiral recognition in addition to molecular
recognition of free amino acids or peptides based on electrostatic interactions
in water, see: (a) Hossain, M. A.; Schneider, H.-J. J. Am. Chem. Soc. 1998,
120, 11208-11209. (b) Bell, T. W.; Khasanov, A. B.; Drew M. G. B.; Filikov,
A.; James, T. L. Angew. Chem., Int. Ed. 1999, 38, 2543-2547. (c) Mizutani,
T.; Wada, K.; Kitagawa, S. J. Am. Chem. Soc. 1999, 121, 11425-11431.
(4) (a) Yashima, E.; Matsushima, T.; Okamoto, Y. J. Am. Chem. Soc. 1997,
119, 6345-6359. (b) Yashima, E.; Maeda, K.; Okamoto, Y. Nature 1999,
399, 449-451.
(10) The ICD intensities increased with the increasing concentration of the
amino acids. The CD titration data were then used to estimate the binding
constants. Sodium acetate buffer (pH 3.8) was used to maintain the pH. Plots
of the CD intensities of the second Cotton of poly-1 as a function of
concentrations of L-Ala and L-Trp gave a saturation binding isotherm at 25
°C. The Hill plot analysis of the data resulted in apparent binding constants
(K) of 9.8 (Ala) and 137 M-1 (Trp) with the Hill coefficient (cooperativity
factor) of 1.0 and 1.1, respectively. The CD titrations with aminosugars and
carbohydrates were performed in imidazole-HCl (pH 6.6) and sodium borate/
HCl (pH 8.6) buffers, respectively. For the Hill plot analysis, see Supporting
Information and the following: Connors, K. A. Binding Constants; John
Wiley: New York, 1987.
(5) Saito, M. A.; Maeda, K.; Onouchi, H.; Yashima, E. Macromolecules
2000, 33, 4616-4618.
(6) Poly-1 was prepared by the polymerization of diethyl (4-ethynylphenyl)-
phosphonate with [Rh(nbd)Cl]2 (nbd ) norbornadiene), followed by hydrolysis
of the ester groups (86% yield). The molecular weight (Mn) was 2.36 × 105
as determined by size exclusion chromatography (see Supporting Information).
(7) (a) Hol, W. G. J.; van Duijnen, P. T.; Berendsen, H. J. C. Nature 1978,
273, 443-446. (b) Nadassy, K.; Wodak, S. J.; Janin, J. Biochemistry 1999,
38, 1999-2017.
(11) For recent examples of chirality recognition of protected amino acids
in organic media, see: (a) Huang, X.; Rickman, B. H.; Borhan, B.; Berova,
N.; Nakanishi, K. J. Am. Chem. Soc. 1998, 120, 6185-6186. (b) Ogoshi, H.;
Mizutani, T. Acc. Chem. Res. 1998, 31, 81-89. (c) Zahn, S.; Canary, J. W.
Org. Lett. 1999, 1, 861-864 and references therein.
(8) Sears, P.; Wong, C.-H. Angew. Chem., Int. Ed. 1999, 38, 2300-2324.
10.1021/ja0160647 CCC: $20.00 © 2001 American Chemical Society
Published on Web 07/10/2001