Helical molecular duplex strands: Multiple hydrogen-bond-mediated assembly of self-complementary oligomeric hydrazide derivatives

Article abstract of DOI:10.1021/jo070525a

(Chemical Equation Presented) Careful examination of the X-ray structure of a ditopic hydrazide derivative 7 led to the concept that with malonyl groups as interhydrazide linkers hydrogen-bonding-mediated molecular duplex strands might be obtained. Comple

Full text of DOI:10.1021/jo070525a

Helical Molecular Duplex Strands: Multiple
Hydrogen-Bond-Mediated Assembly of Self-Complementary
Oligomeric Hydrazide Derivatives
Yong Yang,†,‡ Zhi-Yong Yang,†,‡ Yuan-Ping Yi,†,‡ Jun-Feng Xiang,† Chuan-Feng Chen,*,†
Li-Jun Wan,*,† and Zhi-Gang Shuai*,†
Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences,
Beijing 100080, China, and Graduate School, Chinese Academy of Sciences, Beijing 100049, China
cchen@iccas.ac.cn
ReceiVed March 16, 2007
Careful examination of the X-ray structure of a ditopic hydrazide derivative 7 led to the concept that
with malonyl groups as interhydrazide linkers hydrogen-bonding-mediated molecular duplex strands might
be obtained. Complexation studies between 7, 8, and 9 confirmed this hypothesis. Two quadruple hydrogen-
bonded heterodimers formed, in which spectator repulsive secondary electrostatic interaction was found
to play an important role in determining the stability of the complexes. Extensive studies on 1-4 indicated
that the hydrogen-bonding mode could persist in longer oligomeric hydrazide derivatives with chain
extension from monomer to tetramer. Molecular duplex strands via two to fourteen interstrand hydrogen
bonds were obtained. In addition to affecting the stability of the duplex strands, spectator repulsive
secondary electrostatic interaction also played an important role in determining dynamic behavior of the
duplex strands as exemplified by variable temperature 1H NMR experiments. IR studies confirmed stronger
hydrogen bonding in the longer oligomers. The assemblies of 1-4 on HOPG were also studied by STM
technology. Molecular mechanical calculations further revealed double-helical structures for the longer
oligomers. The results provide new opportunities for development of polymeric helical duplexes with
well-defined structures.
Introduction
multistranded complexes through encoded recognition sites is
the basis of the behavior of biological fibers such as muscle.2
Similar double- and multiple-stranded complexes are ubiquitous
in nature,3 which are the foundation for higher structures and
functions of biomolecules. Artificial construction of similar
structures from unnatural backbones is of fundamental impor-
tance for structural mimicking of biomolecules, may shed some
light on the understanding of the complicated structures of
In nature, DNA stores, transfers, and reproduces genetic
information. The precise function is based on the self-assembly
of two complementary linear strands into a double-stranded
complex via hydrophobic effects, hydrogen bonds, and π-π
stacking interactions.1 The assembly of linear proteins into
* Author to whom correspondence should be addressed. Phone: 86-10-6258-
8936. Fax: 86-10-6255-4449.
† Beijing National Laboratory for Molecular Sciences.
(2) Huxley, H. E. Science 1969, 164, 1356-1366.
(3) Horton, R. H.; Moran, L. A.; Ochs, R. S.; Rawn, D. J.; Scrimgeour,
G. K. Principles of Biochemistry; Prentice Hall International, Inc.: London,
1992.
‡ Graduate School.
(1) Saenger, W. The Principles of Nucleic Acid Structure; Springer-
Verlag: Berlin, 1984.
10.1021/jo070525a CCC: $37.00 © 2007 American Chemical Society
Published on Web 05/26/2007
4936
J. Org. Chem. 2007, 72, 4936-4946

Hydrazide-Based Molecular Duplex Strands
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FIGURE 1. Representation of molecular duplex strands 1-4.
of hydrogen-bonding sites17-23 have gained great success.
Especially Meijer’s ureidopyrimidone (UPy) building block,9,24
characteristic of simplicity in synthesis and exceedingly high
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Here, we report a new class of hydrogen-bonding-
mediated molecular duplex strands from oligomeric hy-
drazide derivatives 1-4 (Figure 1). By applying a strategy
“covalent casting” proposed by Krische et al.18 to a one-
dimensional hydrazide-based hydrogen-bonding motif, a new
family of synthetic homologous duplex molecular strands that
embody orthogonal recognition motifs and up to 14 hydrogen-
bonding sites staying in register for intermolecular interactions
was developed. The stability of the duplex strands could be
adjusted by chain length. New quadruple hydrogen-bonded
heterodimers were also developed. MM calculations revealed
double-helical structures for the longer oligomers. We believe
that the results we present here will provide new structural
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J. Org. Chem, Vol. 72, No. 13, 2007 4937

Yang et al.
FIGURE 4. Chemical structures of 5, 6, 7, 8, and 9 and representation
of heterodimer structures, with proton-labeling scheme indicated.
Spectator repulsive electrostatic interactions are indicated by double
headed arrows (red).
FIGURE 2. Representation of (a) hydrazide-based supramolecular
synthon and (b) its application in the construction of supramolecular
zipper system from ditopic derivative 7. The octyl groups are replaced
with methyl groups for clarity.
FIGURE 3. Representation of supramolecular zipper structure from 9.
FIGURE 5. Stacked partial 1H NMR spectra (300 MHz, 25 °C) of (a)
6, (b) 6 + 9, (c) 9, (d) 5 + 9, and (e) 5. Each at 20 mM in CDCl3.
motifs useful in nanotechnology, nanoscale assembly, and
material science and to some extent structural mimicking of
DNA.
system from ditopic derivative 7. X-ray analysis indicated that
steric hindrance between two adjacent methyl groups rendered
Results and Discussion
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4938 J. Org. Chem., Vol. 72, No. 13, 2007

Hydrazide-Based Molecular Duplex Strands
TABLE 1. Summary of Complexation Induced Chemical Shifts (CIS, ppm)
7-Ha
7-Hb
7-Hc
7-He
9-Ha
9-Hb
9-Hc
8-Ha
8-Hb
8-Hc
8-Hd
8-He
8-Hg
free
7‚9
CIS
8‚9
CIS
10.64
10.73
0.09
9.60
10.48
0.88
9.00
9.11
0.11
2.15
2.25
0.10
10.79
11.20
0.41
10.95
0.16
10.32
11.11
0.79
10.70
0.38
3.59
3.96
0.37
3.77
0.18
10.61
9.38
9.38
7.02
9.02
2.14
10.70
0.09
10.04
0.66
9.55
0.17
7.82
0.80
9.05
0.03
2.19
0.05
173 ( 14 M-1. In the 2D NOESY spectrum of 9, a cross contact
between protons of Hc and Hd was observed, which provided a
1
diagnostic evidence for the zipper structure. H NMR studies
were then performed on 1:1 mixture of 5 and 9, each at 20 mM
in CDCl3. The results are summarized in Figure 5. No obvious
complexation was observed between 5 and 9, which might result
from low acidity of the unacylated NH2 protons. To our surprise,
only weak association was observed when acylated 6 and 9 (each
20 mM) were mixed in CDCl3, considering there were quadruple
1
hydrogen bonds. H NMR titration studies failed to give the
association constant due to signal broadening and overlapping
of NH protons. Strong complexation was observed when 7 and
9, and 8 and 9, were mixed (1:1) in CDCl3, even at a lower
concentration (5 mM). The results are summarized in Figure 6.
Substantial downfield changes for signal of 9-Hb (0.79 ppm for
7‚9 and 0.38 ppm for 8‚9), signal of 7-Hb (0.88 ppm), and
signals of 8-Hb (0.66 ppm) and 8-Hd (0.80 ppm) were observed.
These protons are assumed to participate in intermolecular
hydrogen bonding. Signals for protons located along the edges
which were assumed to participate in intermolecular interactions
all displayed downfield changes (Table 1), especially the signal
for 9-Hc (0.37 ppm for 7‚9 and 0.18 ppm for 8‚9). These
downfield changes can be rationalized by assuming these protons
lied within the deshielding zone of aromatic ring of another
molecule upon complexation. 1H NMR titration studies31 gave
association constants of (1.4 ( 0.1) × 103 M-1 for 7‚9 and
(5.6 ( 0.6) × 102 M-1 for 8‚9, respectively. The differences in
association strength could be attributed to additional secondary
electrostatic repulsive interactions resulting from spectator8a tert-
butoxy oxygen atoms and carbonyl oxygen atoms of 9 (depicted
by double headed arrows in Figure 4). In complexes 6‚9 and
8‚9, there exist two and one spectator repulsive interactions,
respectively, while in complex 7‚9, no spectator repulsive
interaction exists.
Variable temperature 1H NMR studies30 provided additional
evidence for the formation of quadruple hydrogen-bonded
heterodimer structures. Signals for 9-Hb (-9.76 × 10-3 ppm/K
in 7‚9 and -1.1 × 10-2 ppm/K in 8‚9), 7-Hb (-8.88 × 10-3
ppm/K), 8-Hb (-1.45 × 10-2 ppm/K), and 8-Hd (-1.81 × 10-2
ppm/K), which involved in intermolecular hydrogen bonding
in the complexes, showed large temperature coefficients from
288 to 223 K, while signals for 9-Ha (-4.79 × 10-3 ppm/K in
7‚9 and -5.08 × 10-3 ppm/K in 8‚9), 7-Ha (-1.96 × 10-3
ppm/K), 8-Ha (-2.88 × 10-3 ppm/K), and 8-Hc (-3.79 × 10-3
ppm/K), which formed S(6) type32 hydrogen bonds, showed
much smaller temperature coefficients within the same temper-
FIGURE 6. Stacked partial 1H NMR spectra (300 MHz, 25 °C) of (a)
8, (b) 8 + 9, (c) 9, (d) 7 + 9, and (e) 7. Each at 5 mM in CDCl3.
a dihedral angle of 37.0° between two adjacent aromatic rings
(Figure 2). We envisioned that if two methyl carbons converge
into one methene carbon, i.e., two hydrazide groups are
connected by a malonyl group, multiple hydrogen-bond-
mediated supramolecular duplex strands could be expected.
To test this idea, complexation between 5, 6, 7, 8, and 9 was
1
studied. First, concentration-dependent H NMR spectra of 9
indicated that a supramolecular zipper structure similar to that
formed from 7 might form (Figure 3).30 Nonlinear regression
1
analysis20b of the H NMR data of dilution experiments yields
an association constant for chain extension of the aggregate of
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J. Org. Chem, Vol. 72, No. 13, 2007 4939

Yang et al.
FIGURE 7. Chemical structures of 1-4 and representation of molecular duplex strands, with proton-labeling scheme indicated. Spectator repulsive
electrostatic interactions are indicated by double headed arrows (red).
ature range. Small temperature coefficients were also observed
for 9-Hc (-2.63 × 10-3 ppm/K in 7‚9 and -3.85 × 10-3 ppm/K
in 8‚9).
in the duplex strands, were therefore designed and synthesized
(Figure 7). Incorporation of octyloxy groups should lead to the
formation of highly favorable S(6) type hydrogen-bonded rings
and therefore rigidify the backbones and preorganize the
hydrogen-bonding sites staying in register for the formation of
the duplex strands, a strategy extensively used by Gong et al.17
to rigidify molecular conformation of oligoamide derivatives
in the construction of highly stable molecular duplex strands.
Another advantage is good solubility of longer oligomers in
nonpolar solvent CDCl3.
Because of their asymmetric structures, an iterative method
for the preparation of sequentially homologated oligo(hydrazide)
has been devised. The synthetic routes are provided in the
Scheme 1 and Scheme 2. For the synthesis of the key
intermediates 19 and 20, a Boc protective/deprotective strategy
was adopted for the convenience of product purification.
Monoprotected derivative 17 was first synthesized from dihy-
drazide 5 using equimolar di-tert-butyl dicarbonate as acylation
reagent and the separation of the product was convenient.
Further acylation of 17 was performed efficiently by acetyl
chloride in the presence of TEA or by ethyl malonic half ester
with 1-ethyl-3-(3-(dimethyamino)-propyl)carbodiimide hydro-
chloride (EDC‚HCl) as coupling regent. Deprotection of Boc
Two-dimensional NMR spectra30 (NOESY, CDCl3, 300
MHz) provided diagnostic evidence for heterodimer structures.
Intermolecular cross-peaks were observed between 7-Hb and
9-Hb, 7-Hc and 9-Hb, 7-Hc and 9-Hc, 7-He and 9-Hd in a 1:1
mixture of 7 and 9 (each 5 mM), and between 8-He and 9-Hc,
8-Hg and 9-Hd in a 1:1 mixture of 8 and 9 (each 10 mM). The
findings are fully consistent with the quadruply hydrogen-
bonded heterodimer structures. Another direct evidence for
complexation came from ESI-MS (electrospray ionization)
studies. When 1:1 mixtures of 7 and 9, and 8 and 9, in CH2Cl2
and CH3CN (1:1) were analyzed, signals corresponding to the
1:1 complexes (1041.01 for [7+9+Na]+, calcd 1041.56; 1098.85
for [8+9+Na]+, calcd 1099.61) with considerable intensity were
found.
Molecular Duplex Strands. Design Strategy and Syntheses.
The results obtained from complexation studies of 7‚9 and 8‚9
justified the efforts toward preparation of longer molecular
duplex strands with malonyl groups as interhydrazide linkers.
Compounds 1-4, which possess one to seven hydrazide motifs
and consequently two to fourteen intermolecular hydrogen bonds
4940 J. Org. Chem., Vol. 72, No. 13, 2007

Hydrazide-Based Molecular Duplex Strands
SCHEME 1. Synthesis of the Key Intermediates 19 and 20a
a Reagents and conditions: (a) Boc2O/CH2Cl2; (b) acetyl chloride/TEA/CH2Cl2; (c) EDC‚HCl/ethyl malonic half ester/CH2Cl2; (d) HCl/AcOEt.
could then be completed using dry HCl in AcOEt to give the
compounds 19 and 20. With them in hand, the oligomers 1-4
could be synthesized efficiently by iteratively applying coupling
and hydrolysis steps. EDC‚HCl was found to be an efficient
reagent for the coupling of carboxylic acid and hydrazide
derivatives. Moreover, the hydrolysis step performed well in
1:1 THF and water using NaOH as base. In most cases,
purification of the products was convenient, and high yields
(ca 90%) were obtained.30
MS Studies. The formation of the duplex strands was first
confirmed by mass spectrometry.30 In the ESI-MS of 2a and
2b, signals (1671.60 for [2a‚2a+Na]+, calcd 1672; 1788.43 for
[2b‚2b+Na]+, calcd 1788.08) with considerable intensity cor-
responding to the dimeric structures were observed. Signals
(1346.29 for [(2a)3+2Na]2+, calcd 1346.81; 1259.36 for
[(2b)3+2Na]2+, calcd 1259.75) corresponding to the trimeric
structures were also observed. For the longer oligomers, whose
m/z values exceed the detection range of our instrument,
MALDI-TOF MS was adopted. Signals corresponding to the
dimeric structures were also observed, which might indicate the
formation of very stable duplex strands.
1H NMR Studies. The 1H NMR spectra of compounds 1-4
are provided in Figure 8 and Figure 9. At 298 K and a
concentration of 10 mM in CDCl3, two NH signals of 1a appear
at 10.95 ppm (Hb) and 9.23 ppm (Ha), respectively. Upon strand
extension from monomer 1a to dimer 2a, all NH protons exhibit
sharp signals in the downfield area (between 11.79 and 10.89
ppm) at the same conditions. These results clearly indicated that
all NH protons of 2a involved in much stronger hydrogen
bonding. With the strand extension from dimer 2a to trimer 3a
to tetramer 4a, the NH signals all appear between 11 and 12
ppm. No significant downfield shifts were observed, which
might mean that a saturation chemical shift change was obtained
when the chain length extended to dimer 2a. The methylene
protons of malonyl groups and intercarbonyl aromatic protons
both displayed broad signals (for 3a and 4a), which might result
from their proximity in space upon complexation as exemplified
by 2D NOESY experiments and molecular mechanical calcula-
tions (vide infra). Similar results were observed for the tert-
butoxy-terminated oligomers 1b-4b. With the strand extension
from monomer 1b to dimer 2b to trimer 3b, substantial
downfield changes for Ha were observed (from 7.04 to 8.81
ppm to 9.60 ppm). No chemical shift change was observed
with strand extension to tetramer 4b, which might mean a
saturation chemical shift change was obtained only when the
chain length extended to trimer 3b. A fit of the chemical shift
1
data31 of H NMR dilution experiments in CDCl3 to a 1:1
binding mode afforded dimerization constants of (1.6 ( 0.1) ×
10 M-1, (6.4 ( 1.5) × 104 M-1, and (2.0 ( 0.6) × 103 M-1
for 1a‚1a,28 2a‚2a, and 2b‚2b, respectively. No obvious
dimerization of 1b was observed. The differences in association
constants strongly suggested that the self-assemblies of 2a‚2a
and 2b‚2b are highly cooperative, and repulsive secondary
electrostatic interactions resulting from the spectator8a tert-
butoxy oxygen atoms and carbonyl oxygen atoms play an
important role in determining the stability of the duplex strands.
No chemical shift changes were observed when dilution
experiments were carried out on the longer oligomers (from
100 mM to 0.5 mM). Considering the cooperative action of 10
and 14 hydrogen bonds and similar chemical shifts of NH
protons, the association constants for 3‚3 and 4‚4 should be no
1
lower than 105 M-1. H NMR dilution experiments on the
longer oligomers in more polar solvents (5% DMSO/CDCl3 and
5% CH3CN/CDCl3) failed to give the association constants due
to signal overlapping and small chemical shift changes (<0.1
ppm).
1
Variable temperature H NMR experiments30 revealed dif-
ferent molecular dynamics for the tert-butoxy-terminated oli-
gomers 1b-4b and methyl-terminated oligomers 1a-4a. At 228
K and a concentration of 10 mM in CDCl3, for 2a-4a, multiple
J. Org. Chem, Vol. 72, No. 13, 2007 4941

Yang et al.
SCHEME 2. Synthetic Routes for Compounds 1-4 and 9a
a
Reagents and conditions: (a) Boc2O/CH2Cl2; (b) malonic acid/EDC‚HCl/CH2Cl2; (c) ethyl malonic half ester/EDC‚HCl/CH2Cl2; (d) i, THF/H2O/
NaOH; ii, HCl; (e) 20/EDC‚HCl/CH2Cl2; (f) 19a/EDC‚HCl, CH2Cl2; (g) 17a/EDC‚HCl/CH2Cl2; (h) 19b/EDC‚HCl/CH2Cl2.
sets of signals were observed. Especially the NH signals, which
appeared in the downfield area between 10.9 and 12.5 ppm at
298 K, exhibited complicated pictures in this field. New minor
signals of NH protons appear in the area between 8 and 9 ppm,
which might correspond to NH protons not involved in hydrogen
bonding. New signals for malonyl protons also appeared. For
4942 J. Org. Chem., Vol. 72, No. 13, 2007

Hydrazide-Based Molecular Duplex Strands
FIGURE 8. Stacked partial spectra of (a) 1a (5 mM), (b) 2a (10 mM),
(c) 3a (10 mM), (d) 4a (10 mM) at 298 K and (e) 1a (5 mM), (f) 2a
(10 mM), (g) 3a (10 mM), (h) 4a (10 mM) at 228 K in CDCl3, 600
MHz.
FIGURE 10. NOESY spectrum (10 mM, 600 MHz, 298 K, CDCl3)
of 2a, with some intermolecular cross contacts highlighted.
2b-4b at the same conditions, signals for the NH protons only
exhibited downfield shifts and sharpening. No new signals were
observed. There might exist a dimeric-polymeric equilibrium
for the methyl-terminated oligomers.30
2D NMR Studies. Two-dimensional (2D) NMR (NOESY,
FIGURE 11. NOESY spectrum (10 mM, 600 MHz, 298 K, CDCl3)
of 2b, with some intermolecular cross contacts highlighted.
any cross-peaks to be observed, the signals must correspond to
intermolecular contacts between the two molecules constituting
the duplex strands. For 2b, there are some differences. In
addition to cross contacts between Hh and Hg, Ha, and He, which
might result from the centrosymmetric dimeric structure, cross
contacts between Hc and He, and Ha and Hc, were also observed.
There should exist an equilibrium as depicted in Scheme 3. For
the longer oligomers, similar results were observed. Cross
contacts between Hh (Hh′, Hh′′) and Hg (Hg′, Hg′′), between Hj
and Hk for the methyl-terminated oligomers were undoubtedly
observed. But we cannot assign NH protons precisely due to
signal overlapping. The NOESY and TOCSY spectra were
provided in Supporting Information.
FIGURE 9. Stacked partial spectra of (a) 1b, (b) 2b, (c) 3b, (d) 4b at
298 K and (e) 2b, (f) 3b, (g) 4b at 228 K, each at 10 mM in CDCl3,
600 MHz.
CDCl3, 600 MHz) studies provided the most diagnostic evidence
for formation of the duplex strands in solution. The results of
2a (Figure 10) and 2b (Figure 11) are elaborated below. The
NH signals have been assigned by NOESY and TOCSY
experiments. For 2a, important contacts were observed between
protons Hk and Hj, Hh and Hc, Hh and He, Ha and He, and Hh
and Hg. Because within the same molecule of 2a distances
between the above-mentioned protons are much too long for
J. Org. Chem, Vol. 72, No. 13, 2007 4943

Yang et al.
FIGURE 12. Partial IR spectra of (a) 1a, (b) 2a, (c) 3a, and (d) 4a (KBr).
SCHEME 3. Proposed Equilibrium of 2b in CDCl3
IR Studies. Infrared (IR) spectroscopic data provided ad-
ditional evidence for the stability of the duplex strands of
different chain lengths. Specifically, there were three NH-
stretches at 3345, 3204, and 3090 cm-1 in the solid-state (KBr)
spectra of 1a. With the strand extension from monomer
1a to dimer 2a to trimer 3a, the intensity of the NH-stretch at
∼3340 cm-1 decreased, while the intensity of the hydrogen-
bonded NH-stretch increased. When the strand extended
to tetramer 4a, no stretch at ∼3340 cm-1 was observed
(Figure 12). Thesefindings might indicate stronger hydrogen
bonding for the longer oligomers. Similar results were observed
for the tert-butoxy-terminated oligomers. The IR spectra of 1-4
in dry chloroform solution (10 mM) provided similar results as
observed in the solid-state spectra.30 The results clearly showed
that the duplex strands formed both in solution and in the solid
state.
Calculation. Though attempt to grow a single-crystal suitable
for X-ray analysis failed, even with isobutyloxy-substituted
derivatives, molecular mechanical calculations provided infor-
mation on the conformations of the duplex strands. For
convenience, the long octyl groups were replaced by methyl
groups. The geometries of the compounds were optimized with
molecular mechanical method implemented in software pro-
grams from Accelrys. Energy-minimization calculations were
performed with the Discover program using the COMPASS
force field, and the graphical displays were generated with the
4944 J. Org. Chem., Vol. 72, No. 13, 2007

Hydrazide-Based Molecular Duplex Strands
FIGURE 14. STM images of (a) 1a, (b) 2a, (c) 3a, and (d) 4a on
HOPG.
FIGURE 13. Energy-minimized conformations of (a) 4a‚4a and (b)
4b‚4b.
Materials Visualizer.33 Results for 4a and 4b are provided in
Figure 13. The S(6) type hydrogen bonds indeed rigidified the
backbones. S(5) type hydrogen bonds from NH protons to
malonyl oxygen atoms were also presented, which further
rigidified the backbones. Docking a single strand with itself
revealed that two strands wound up to form a double-helical
structure. The methylene protons of malonyl groups and
intercarbonyl aromatic protons came into proximity upon
dimerization, which was fully consistent with the NOESY
experiments. Secondary electrostatic repulsive interactions
resulting from spectator tert-butoxy oxygen atoms and carbonyl
oxygen atoms in 4b‚4b lead to differences in length for the
outer hydrogen bonds (dH···O: 1.879 Å for 4a‚4a and 1.933 Å
for 4b‚4b).
STM Studies. The self-assemblies of 1-4 on HOPG (high
oriented pyrolytic graphite) were also studied by STM (scanning
tunneling microscope) technology.34 The results are summarized
in Figure 14 and Figure 15. For 1a and 2a, the duplex strands
were indeed observed. But for 3a and 4a, there were no clear
(33) Accelrys, MS Modeling Getting Started, Accelrys Software Inc.:
San Diego, 2004.
(34) (a) Giancarlo, L. C.; Flynn, G. W. Acc. Chem. Res. 2000,
33, 491-501. (b) de Feyter, S.; Gesquie`re, A.; Abdel-Mottaleb,
M. M.; Grim, P. C. M.; de Schryver, F. C. Acc. Chem. Res. 2000, 33, 520-
531.
FIGURE 15. STM images of (a) 2b, (b) 3b, and (c) 4b on HOPG.
gaps for the expected duplex strands. Only polymeric duplex
strands were observed. These findings probably came from the
J. Org. Chem, Vol. 72, No. 13, 2007 4945

Yang et al.
General Procedure for Deprotection of Boc Group (proce-
dure B). To a solution or suspension of Boc derivatives in ethyl
acetate (usually 10 mL per mmol) was bubbled dry HCl gas for 2
h. After the solvent was evaporated under reduced pressure, the
residue dissolved in CH2Cl2. The mixture was then neutralized with
TEA, washed with water, and dried over anhydrous Na2SO4. The
crude product was purified by column chromatography (silica gel,
usually AcOEt:MeOH ) 10:1 as eluent). If necessary, crystallization
from hot acetonitrile was used to obtain pure product.
General Procedure for Hydrolysis of Esters (procedure C).
To a solution of ester in THF (usually 10 mL per mmol) was added
a solution of NaOH (usually 3 equiv) in equivolume of water
(relative to THF). Then the mixture was stirred at room temperature,
and the reaction was monitored by TLC. The reaction completed
in 5 h, and sometimes heating was necessary for the completion of
the reaction. The organic solvent was evaporated under reduced
pressure, and the residue was acidified with concentrated HCl. Upon
acidification, a white solid precipitated from the solution, and the
crude product was collected by filtration. The pure product as a
white solid was obtained by recrystallization from hot acetonitrile.
different dynamic behaviors in solution and on the surface. For
tert-butoxy-terminated oligomers 2b and 3b, the results are
similar to that for 2a. With chain extension to 4b, a twisted
conformation was observed. These observations are consistent
with those of the MM calculations.
Conclusions
Results from model studies of 7‚9 and 8‚9 led to discovery
of a new family of molecular duplex strands from hydrazide-
based oligomers with malonyl groups as linkers. Preorganization
by intramolecular hydrogen bonding and highly cooperative
intermolecular interactions by up to 14 hydrogen bonds resulted
in high stability of the duplex stands. Molecular mechanical
calculations revealed that two strands wound up to form a
double-helical structure, akin to that of DNA. Different dynami-
cal behaviors were also observed for the tert-butoxy-terminated
oligomers and methyl-terminated oligomers. We believe that
the results presented here will provide new opportunities for
development of polymeric helical duplexes of well-defined
structures and new structural motifs useful in nanoscale as-
sembly, which are underway.
Full experimental procedures and characterization data for new
compounds are provided in the Supporting Information.
Acknowledgment. We thank the National Natural Science
Foundation of China, National Basic Research Program
(2007CB808004) and the Chinese Academy of Sciences for
financial support.
Experimental Section
General Procedure for the Coupling Reaction of Carboxylic
Acids and Hydrazide Derivatives (procedure A). To an equimolar
mixture of a carboxylic acid and a hydrazide derivative in dry CH2-
Cl2 (usually 10 mL per mmol) in an ice-water bath was added 1.1
or 1.2 equiv of EDC‚HCl. The mixture was stirred at room
temperature for 5 h and then concentrated under reduced pressure.
The pure product as a white solid was obtained by recrystallization
from hot acetonitrile.
Supporting Information Available: Experimental procedures
and characterization data for new compounds. Detailed information
on the evaluation of the duplex strands. This material is available
free of charge via the Internet at http://pubs.acs.org.
JO070525A
4946 J. Org. Chem., Vol. 72, No. 13, 2007