Supramolecular substitution reactions between hydrazide-based molecular duplex strands: Complexation induced nonsymmetry and dynamic behavior

Article abstract of DOI:10.1021/jo801139p

(Chemical Equation Presented) Supramolecular substitution reactions between hydrazide-based oligomers 1a-c and 2a-c were systematically investigated. Each oligomer existed as hydrogen-bonding mediated molecular duplex strands or a polymeric zipper structure in apolar solvents. But when another oligomer with complementary hydrogen bonding sites was added, a heterodimer structure formed due to supramolecular substitution reaction driven by the formation of more hydrogen bonds, which was evidenced by NMR experiments, sometimes gel-sol transition. When a nonsymmetric oligomer and a symmetric oligomer were involved, complexation-induced nonsymmetry was observed. When two nonsymmetric oligomers were involved, two hydrogen-bonded isomers were observed in solution. Variable-temperature ¹H NMR experiments further revealed unique dynamic behavior for the individual oligomer and the complexes. When diacetyl-terminated oligomer 1c was involved, slides perpendicular to hydrogen bonds between two constituent molecules were observed, which led to complicated ¹H NMR spectra at lower temperature; otherwise, high selectivity was obtained. Combined with the results we reported previously, a detailed picture of the structure-property relationship for our hydrazide-based oligomers was depicted, which would provide guidelines for the design of hydrazide-based fine-tuning functional materials.

Full text of DOI:10.1021/jo801139p

Supramolecular Substitution Reactions between Hydrazide-Based
Molecular Duplex Strands: Complexation Induced Nonsymmetry
and Dynamic Behavior
Yong Yang, Jun-Feng Xiang, Min Xue, Hai-Yu Hu, and Chuan-Feng Chen*
Beijing National Laboratory for Molecular Sciences, Center for Chemical Biology, Institute of Chemistry,
Chinese Academy of Sciences, Beijing 100190, China
cchen@iccas.ac.cn
ReceiVed May 26, 2008
Supramolecular substitution reactions between hydrazide-based oligomers 1a-c and 2a-c were
systematically investigated. Each oligomer existed as hydrogen-bonding mediated molecular duplex strands
or a polymeric zipper structure in apolar solvents. But when another oligomer with complementary
hydrogen bonding sites was added, a heterodimer structure formed due to supramolecular substitution
reaction driven by the formation of more hydrogen bonds, which was evidenced by NMR experiments,
sometimes gel-sol transition. When a nonsymmetric oligomer and a symmetric oligomer were involved,
complexation-induced nonsymmetry was observed. When two nonsymmetric oligomers were involved,
1
two hydrogen-bonded isomers were observed in solution. Variable-temperature H NMR experiments
further revealed unique dynamic behavior for the individual oligomer and the complexes. When diacetyl-
terminated oligomer 1c was involved, slides perpendicular to hydrogen bonds between two constituent
1
molecules were observed, which led to complicated H NMR spectra at lower temperature; otherwise,
high selectivity was obtained. Combined with the results we reported previously, a detailed picture of
the structure-property relationship for our hydrazide-based oligomers was depicted, which would provide
guidelines for the design of hydrazide-based fine-tuning functional materials.
Introduction
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10.1021/jo801139p CCC: $40.75
Published on Web 07/24/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 6369–6377 6369

Yang et al.
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FIGURE 1. Chemical structures of hydrazide-based oligomers 1a-c
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Hydrazide-Based Molecular Duplex Strands
CHART 1. Representation of Li’s Hydrazide-Based Quadruply Hydrogen-Bonded Heterodimers (a, b)22 and Ours (c)34
SCHEME 1. Synthetic Routes for 1b, 2a, and 2b
strength and specificity as demonstrated by natural biomolecules.
Investigations along this route will provide mimics of biomol-
ecules and shed some light on the understanding of the
complicated structures and functions as demonstrated by them.
Eventually, new materials with functional properties can also
be expected from these unnatural counterparts.
Recently, Li et al. reported a new type of hydrazide-based
quadruply hydrogen-bonded heterodimer system (Chart 1),22 in
which S(6)-type hydrogen bonding and a bulky cyclohexyl
group were introduced to preorganize hydrogen-bonding sites
and to block unwanted hydrogen-bonding sites, even though
two hydrogen-bonded isomers were observed in solution.
Similarly, by introduction of S(6)-type hydrogen bonding to
preorganize hydrogen bonding sites and to block unwanted
hydrogen-bonding sites, we34 also reported a new kind of
hydrazide-based quadruply hydrogen-bonded hererodimer with
geometrically complementary m-phenylene and malonyl groups
as spacers (Chart 1). The only heterodimer structure was
exclusively observed in solution. Based on the study of this
model system, we34 further constructed a new family of
hydrogen-bonded molecular duplex strands from self-assembly
of hydrazide-based oligomers by applying “covalent casting”21
to a hydrazide-based one-dimensional hydrogen-bonding
motif.35,36 Different dynamic behavior and association constants
were observed for acetyl-terminated series and Boc-terminated
series. From di-Boc-terminated series, variable-temperature 1H
NMR experiments revealed a shuttle-like dynamic process of
the two constituent molecules of the duplex strands.37 Molecular
mechanical calculations revealed double-helical structures for
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J. Org. Chem. Vol. 73, No. 16, 2008 6371

Yang et al.
FIGURE 2. Representation of shuttle-like dynamic process of 2a·2a and supramolecular substitution reactions between 1a-c and 2a.
the duplex strands.34,37 Gelation was observed with diacetyl-
terminated 1c and dinaphthyl-terminated 2c. A multipoint
recognition-directed supramolecular substitution reaction led to
mutual responsive LMOGs, and variable-temperature 1H NMR
experiments revealed unique dynamic behavior for the com-
plex.38 In this paper, we will systematically investigate su-
pramolecular substitution reactions between 1a-c and 2a-c
(Figure 1). Dynamic behavior for each duplex strands is also
explored. Combined with the results we reported previously,
we try to depict a detailed picture of the structure-property
relationship for our hydrazide-based oligomers, which, we
believe, will provide guidelines for the design of hydrazide-
based fine-tuning functional materials.
Results and Discussion
Synthesis. Compounds 1a,37 1c,38 and 2c38 were synthesized
previously. Compound 1b was synthesized via coupling reaction
of compound 4 and compound 5,34 while compound 4 was
obtained via hydrolysis of compound 3.34 Compounds 2a and
2b were synthesized via coupling reactions of 634 and 734 and
838 and 9,34 respectively (Scheme 1). EDC ·HCl was found to
be an efficient coupling reagent for the reaction between
carboxylic acid and hydrazide derivatives. In all cases, high
yields were obtained.
Supramolecular Substitution Reactions between 2a and
1a-c. Though ubiquitous and very important for many biologi-
cal processes in nature, multipoint recognition presents a great
challenge for chemists. As we reported previously, a multipoint
recognition-directed supramolecular substitution reaction be-
tween 1c and 2c led to gel-sol transition.38 In this paper, we
tried to investigate supramolecular substitution reactions such
as X·X +Y·Y f 2X·Y or Xn +Yn f nX·Y or 2Xn + nY·Y
f 2nX·Y systematically and exhaustively between 1a-c and
2a-c, which possessed complementary hydrogen bonding sites.
First, as in the case of 1c and 2c, addition of an equimolar 2a
FIGURE 3. Stacked partial 1H NMR spectra of (a) 1a and 2a, (b) 1a,
(c) 1b, (d) 1b and 2a, (e) 2a, and (f) 1cand 2a at 298 K, 600 MHz,
each 10 mM in CDCl3.
into the viscous solution from 1c in CHCl3 resulted in a clear
solution. This phenomenon might suggest that the polymeric
zipper structure derived from 1c disrupted upon interaction with
2a to form a discrete heterodimer structure (Figure 2). 1H NMR
mixing experiments and 2D NOESY experiment further con-
1
firmed the hypothesis. The H NMR spectrum of 1c alone in
CDCl3 at 10 mM cannot be recorded because the solutin is very
viscous. But a clear solution of 1c and 2a in CDCl3 (each 10
mM) gave a well-resolved spectrum (Figure 3f). A cross contact
between terminal methyl protons 1c-Hf and 2a-He (He′) was
undoubtedly observed in the 2D NOESY spectrum (Figure 4b).
1
Variable-temperature H NMR experiments revealed unique
dynamic behavior. A similar shuttle-like dynamic process for
di-Boc-terminated series37 was observed for 2a. At 298 K, a
dimerization self-assembly mode for 2a was undoubtedly
established by 2D NOESY experiments (Figure 4a). Cross
(38) Yang, Y.; Chen, T.; Xiang, J.-F.; Yan, H,-J.; Chen, C.-F.; Wan, L.-J.
Chem. Eur. J. 2008, 14, 5742–5746.
6372 J. Org. Chem. Vol. 73, No. 16, 2008

Hydrazide-Based Molecular Duplex Strands
FIGURE 4. 2D NOESY spectra of (a) 2a, 298 K, (b) 1c and 2a, 298 K, (c) 1b and 2a, 298 K, and (d) 1b and 2a, 223 K, each 10 mM in CDCl3,
600 MHz.
lower temperature (Figure 5f), multiple sets of signals were
observed in the NH region between 10.9 and 12.6 ppm. New
minor signals also appeared in the area between 7.5 and 8.5
ppm, which might correspond to NHs not involved in hydrogen
bonding. These findings might suggest intermolecular slide
perpendicular to hydrogen bonds as observed for acetyl termi-
nated series34 and 1c·2c.38 2D NOESY experiments (Figure
4b) also provided another evidence for the conclusion: a minor
cross contact between 1c-Hf and the h zone was clearly
observed.
Supramolecular substitution reactions between 1a and 2a and
1
1b and 2a were also analyzed by H NMR and 2D NOESY
experiments. Substantial downfield shifts (>2 ppm) were
1
observed for the NHs (Hd) adjacent to Boc groups in the H
NMR spectra of 1:1 mixtures in CDCl3 (each 10 mM) at 298
K (Figure 3a and 3d), which might indicate strong intermolecular
association. Intensive contacts were observed between g zone
and h zone in the 2D NOESY spectra.39 Especially for a mixture
of 1b and 2a, a cross contact between terminal methyl groups
1b-Hf and 2a-He (He′) was observed (Figure 5c), which provided
FIGURE 5. Stacked partial 1H NMR spectra of (a) 1a and 2a, (b) 1a,
diagnostic evidence for the heterodimer structure. With lowering
(c) 1b, (d) 1b and 2a, (e) 2a, and (f) 1c and 2a at 223 K, 600 MHz,
each 10 mM in CDCl3.
1
of temperature in the H NMR spectrum (Figure 5a) of 1:1
mixture (each 10 mM) of 1a and 2a, only NHs adjacent to Boc
groups displayed signal sharpening and minor position shifts.
In the case of nonsymmetric oligomer 1b and symmetric
oligomer 2a (1:1 mixed, each 10 mM in CDCl3), complexation-
induced nonsymmetry was observed. Signals for terminal
aromatic protons of 2a displayed broad peaks at 298 K and
two sets of peaks at 223 K, especially those for He and He′
(Figure 5d). 2D NOESY experiment at 223 K revealed that the
contacts between Hg and Hh andHg (Hg′) and He (He′) were
observed. At 223 K, a signal corresponding to methylene protons
(g zone) of malonyl groups split into two peaks: one shifted
downfield and one shifted upfield. Partial signals for NHs also
displayed upfield shift. Terminal aromatic protons displayed
broad signals. Two sets of signals were observed for Hd and
Hd′ (Figure 5e). All of these findings are consistent with a
shuttle-like dynamic process as depicted in Figure 2. When a
mixture of 1c and 2a in CDCl3 (each 10 mM) was analyzed at
(39) See the Supporting Information for more details.
J. Org. Chem. Vol. 73, No. 16, 2008 6373

Yang et al.
displayed broad signals at about 9.75 ppm (Figure 6a), while
at 223 K, three peaks with an intensity ratio of 1:1:1 each
presenting in the h zone and i zone and NHs adjacent to the
Boc groups displayed four sharp signals (Figure 8a). These
temperature-dependent changes may also be attributed to
nonsymmetry of 1a upon complexation with nonsymmetric 2b.
When two nonsymmetric oligomers 1b and 2b were involved,
the 2D NOESY spectrum (298 K) revealed contacts between
1b-Hf and 2b-He, 1b-Hf and 2b-Hd (Figure 7c). There should
exist two isomers 1b·2b and (1b·2b)′ for the heterodimer, as
depicted in Figure 9. Variable-temperature 1H NMR experiments
on a 1:1 mixture of 1b and 2b further confirmed our hypothesis.
At 223 K, two sets of signals were observed, especially those
for NHs adjacent to Boc group, 2b-He (He′) and 2b-Hd (Hd′),
1b-Hf (Hf′), h zone, and i zone (Figure 8d). In the 2D NOESY
spectrum of 1:1 mixed 1b and 2b in CDCl3 (each 10 mM) at
223 K, contacts between 1b-Hf′ and 2b-Hd, 1b-Hf and 2b-He
were observed (Figure 7d), which provided another diagnostic
evidence for the existence of two hydrogen bonded isomers.
These findings suggest that exchange process between the two
hydrogen bonding isomers 1b·2b and (1b·2b)′ are prohibited
or slow on the NMR time scale at this temperature. The ratio
for the two isomers is 1b·2b:(1b·2b)′ ) 2:3 (results based on
integration of signals for He and He′, Hd and Hd′ at 223 K). A
slight selectivity was obtained.
Supramolecular Substitution Reactions Between 2c and
1a-c. When we systematically investigated supramolecular
substitution reactions between 1a-c and 2c, different results
were obtained. As reported previously, 10 mM (ca. 0.8%, w/w)
2c in CHCl3 formed a gel, and addition of equimolar another
gelator 1c led to gel-sol transition.38 Variable-temperature 1H
NMR experiments revealed slides perpendicular to hydrogen
bonds between the two constituent molecules of the complex
(Figure 10c,d). Addition of equimolar 1a into the gel from 2c
in CDCl3 also led to gel-sol transition, and the complex 1a·2c
displayed a well-resolved spectrum (Figure 10a). The NHs of
1a adjacent to Boc displayed large downfield shifts and lowering
of temperature only led to signal sharpening and minor shifts
(Figure 10a,b).41 To our surprise, 1:1 mixed 1b and 2c in CDCl3
could not lead to a gel-sol transition39 as in the cases of 1a·2c
and 1c·2c. This exceptional case might need further investigation.
FIGURE 6. Stacked partial 1H NMR spectra of (a) 1a and 2b, (b) 1a,
(c) 1b, (d) 1b and 2b, (e) 2b, and (f) 1c and 2b at 298 K, 600 MHz,
each 10 mM in CDCl3.
terminal methyl group 1b-Hf only contacted with 2a-He′ (Figure
4d). These findings can be rationalized by considering the eight
hydrogen-bonded complex 1b·2a as a covalently bonded
molecule: the nonsymmetric nature of 1b induced nonsymmetry
of 2a upon complexation, just as one component of a molecule
induced nonsymmetry of another component of the same
molecule.
Supramolecular Substitution Reactions between 2b and
1a-c. Supramolecular substitution reactions between 1a-c and
2b and dynamic behavior of the complexes were also analyzed
by NMR experiments. As found in the cases of 1c and 2a (vide
supra) and 1c and 2c,38 addition of one equimolar 2b into the
viscous solution of 1c in CDCl3 also resulted in a clear solution,
1
and H NMR experiments revealed a well-resolved spectrum
(Figure 6f). Cross contacts between 1c-Hf and 2b-Hd, 2b-He
were undoubtedly observed in the 2D NOESY spectrum, and
contact between 1c-Hf and h zone was also observed (Figure
7b). These findings might indicate slide between the two
constituent molecules of the complex, which was further
confirmed by variable-temperature 1H NMR experiments (vide
infra). 2D NOESY experiments on 2b (10 mM in CDCl3)
revealed contacts between Hd, He, Hh, and g zone (Figure 7a).
In the 1H NMR spectrum of 2b at 223 K (Figure 8e), multiple
sets of signals were observed, especially two signals for Hh and
three signals for He (He′). On thes basis of these findings, a
complicated equilibrium for 2b in CDCl3 as depicted in Figure
9 was proposed. Form X and form X′, form Y and form Y′ are
degenerated states, and there exist shuttle-like dynamic processes
as observed for di-Boc-terminated series37 and 2a (vide supra),
while form X, form X′, and form Y, formY′ can be viewed as
hydrogen-bonding isomers. Variable-temperature 1H NMR
experiments on a 1:1 mixture of 1c and 2b (each 10 mM in
CDCl3) revealed dynamic behavior for the complex similar to
those for complexes 1c·2a (vide supra), 1c·2c,38 and acetyl-
terminated series:34 multiple sets of signals were observed at
223 K (Figure 8f). Complexation-induced nonsymmetry was
also observed with nonsymmetric 2b and symmetric 1a. At 298
K, there were two peaks with an intensity ratio of 1:2, each
Conclusions
In conclusion, we systematically and exhaustively investigated
supramolecular substitution reactions between hydrazide-based
oligomers with complementary hydrogen-bonding sites. In
particular, when a symmetric oligomer and a nonsymmetric
oligomer were involved, complexation-induced nonsymmetry
was observed, just as one component of a molecular induced
nonsymmetry of another component of the same molecule:
cooperative action of multiply hydrogen bonds can be as strong
as covalent bonds; when two nonsymmetric oligomers were
involved, two hydrogen-bonded isomers were observed. Dy-
namic behavior for the molecular duplex strands was also
investigated by variable-temperature 1H NMR experiments.
(40) (a) Wilcox, C. S. In Frontiers in Supramolecular Organic Chemistry
and Photochemistry; Schneider, H.-J., Durr, H. Eds.; VCH: New York, 1991;
pp 123-143. (b) Conners, K. A. Binding Constants: The Measurement of
Molecular Complex Stability; Wiley-Interscience: New York, 1987.
(41) In the variable-temperature 1H NMR spectra for C2 · H3, signals in the
h zone and i zone split into three peaks. We do not understand the reasons for
this phenomenon at present. Perhaps this comes from the double helical
conformation of the complex. See the Supporting Information for more details.
1
presenting in the h zone and i zone of H NMR spectrum of
1:1 mixture of 2b and 1a, and NHs adjacent to the Boc groups
6374 J. Org. Chem. Vol. 73, No. 16, 2008

Hydrazide-Based Molecular Duplex Strands
FIGURE 7. 2D NOESY spectra of (a) 2b, 298 K, (b) 1c and 2b, 298 K, (c) 1b and 2b, 298 K, and (d) 1b and 2b, 223 K, each 10 mM in CDCl3,
600 MHz.
static repulsive interaction inherent with Boc group can affect
the association stability of the molecular duplex strands; and
(3) gelation is observed with diacetyl-terminated oligomer 1c
and dinaphthyl-terminated oligomer 2c, and supramolecular
substitution reaction leads to mutual responsive LMOGs. We
believe that the structure-property relationship revealed here
will provide guidelines for the design of hydrazide-based fine-
tuning functional materials, the development of environment-
responsive supramolecular polymers, and the construction of
complex supramolecular structures, which are underway in our
laboratory.
Experimental Section
Synthesis of Compound 4. To a suspension of compound 3
(1.33 g, 2 mmol) in C2H5OH (15 mL) was added a solution of
NaOH (0.24 g, 6 mmol) in 15 mL of water. The mixture was then
stirred at room temperature, and the reaction was monitored by
TLC. The reaction was complete in 5 h. 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.
FIGURE 8. Stacked partial 1H NMR spectra of (a) 1a and 2b, (b) 1a,
(c) 1b, (d) 1b and 2b, (e) 2b, and (f) 1c and 2b at 223 K, 600 MHz,
each 10 mM in CDCl3.
The pure product as a white solid was obtained by recrystallization
1
from hot acetonitrile (1.21 g, 95%). Mp: 163-164 °C. H NMR
(300 MHz, DMSO-d6, 298 K, TMS): δ 12.49 (s, 1H, COOH), 10.96
(d, J ) 3.7 Hz, 1H, H-N), 10.20 (d, J ) 3.2 Hz, 1H, H-N), 9.40 (s,
1H, H-N), 9.02 (s, 1H, H-Ar), 8.33 (s, 1H; H-N), 6.81 (s, 1H, H-Ar),
4.29-4.22 (m, 4H, OCH2), 3.31 (s, 2H, COCH2CO), 1.88-1.77
(m, 4H, CH2), 1.43-1.26 (m, 29H, CH2 and OC(CH3)3), 0.86 (t, J
) 6.9 Hz, 5.1 Hz, 6H, CH3). 13C NMR (75 MHz, DMSO-d6, 298
K, TMS): δ 168.8, 164.2, 162.3, 160.6, 160.3, 160.0, 155.1, 134.1,
114.0, 112.4, 97.8, 79.1, 69.6, 69.3, 31.23, 31.19, 28.8, 28.63, 28.61,
28.3, 28.0, 25.5, 22.09, 22.06, 13.89, 13.88. IR (KBr, cm-1): 3369,
Combined with the results we reported previously, by systematic
modificationonthestructures,adetailedpictureofstructure-property
relationship for our hydrazide-based molecular duplex strands
can be depicted: (1) Boc groups affect the dynamic behavior of
the molecular duplex strands substantially: when a Boc group
is involved, high selectivity is obtained; otherwise, slide
perpendicular to the hydrogen bonds leads to a complicated 1H
NMR spectrum at low temperature, which might come from a
dimer-polymer equilibrium; (2) spectator secondary electro-
J. Org. Chem. Vol. 73, No. 16, 2008 6375

Yang et al.
FIGURE 9. Representation of equilibrium for 2b in CDCl3 and supramolecular substitution reaction between nonsymmetric monomers 1b and 2b.
3317, 3219, 2926, 2859, 1740, 1713, 1616, 1467 cm-1. MS
(MALDI-TOF): m/z 659.1 [M + Na]+, 675.0 [M + K]+. MS (ESI):
m/z 635.06 [M - H]-. Anal. Calcd for C32H52N4O9: C, 60.36; H,
8.23; N, 8.80. Found: C, 60.21; H, 8.27; N, 9.14.
28.2, 26.1, 26.0, 25.9, 25.8, 22.6, 20.6, 14.1. IR (KBr, cm-1): 3344,
3227, 2928, 2859, 1631, 1458 cm-1. MS (ESI): m/z 1110.09 [M]-.
Anal. Calcd for C58H94N8O13: C, 62.68; H, 8.52; N, 10.08. Found:
C, 62.61; H, 8.48; N, 10.22.
Synthesis of 1b. To a solution of compound 4 (255 mg, 0.4
mmol) and compound 5 (197 mg, 0.4 mmol) in CH2Cl2 with cooling
in an ice-water bath was added EDC ·HCl (116 mg, 0.6 mmol).
The mixture was stirred at room temperature for 5 h. The solvent
was evaporated under reduced pressure, and the residue was
recrystallized from hot acetonitrile to give the product as a white
solid (0.38 g, 87%). Mp: 132-133 °C. 1H NMR (300 MHz, CDCl3,
298 K, TMS): δ 11.78 (d, J ) 8.0 Hz, 1H, N-H), 11.49 (d, J ) 8.3
Hz, 1H, N-H), 11.22 (d, J ) 8.2 Hz, 1H, NH), 11.14 (d, J ) 8.1
Hz, 1H, NH), 10.97 (d, J ) 8.2 Hz, 1H, N-H), 10.88 (d, J ) 8.1
Hz, 1H, N-H), 9.43 (s, 1H, N-H), 9.12 (s, 1H, Ar-H), 9.03 (s, 1H,
Ar-H), 7.22-7.05 (br, 1H, N-H), 6.51 (s, 2H, Ar-H), 4.25-4.10
(m, 10H, OCH2 and COCH2CO), 2.38 (s, 3H, COCH3), 2.15-1.93
(m, 8H, CH2), 1.55-1.20 (m, 49H, CH2 and OC(CH3)3), 0.90-0.83
(m, 12H, CH2). 13C NMR (75 MHz, CDCl3, 298 K, TMS): δ 165.2,
162.9, 160.9, 160.8, 160.5, 157.2, 157.0, 155.1, 136.8, 112.9, 112.3,
111.9, 96.3, 81.3, 70.3, 38.9, 31.7, 29.3, 29.2, 29.1, 29.0, 28.8, 28.6,
Synthesis of 2a. To a solution of compound 6 (0.56 g, 1.6 mmol)
and compound 7 (0.36 g, 0.8 mmol) in CH2Cl2 with cooling in an
ice-water bath was added EDC ·HCl (0.38 g, 2.0 mmol). The
mixture was stirred at room temperature for 5 h. The solvent was
evaporated under reduced pressure, and the residue was recrystal-
lized from hot acetonitrile to give the product as a white solid (0.78
1
g, 88%). Mp: 95-96 °C. H NMR (300 MHz, CDCl3, 298 K,
TMS): δ 11.64 (s, 2H, H-N), 11.38 (s, 2H, H-N), 11.13 (s, 2H,
H-N),10.92 (s, 2H, H-N), 9.13 (s, 1H, H-Ar), 8.83 (s, 1H, H-Ar),
8.23 (d, J ) 7.7 Hz, 1H, H-Ar), 8.03 (d, J ) 7.8 Hz, 1H, H-Ar),
7.73 (d, J ) 8.1 Hz, 1H, H-Ar), 7.54-7.23 (m, 3H, H-Ar), 7.24 (s,
1H, H-Ar), 7.10 (t, J ) 7.6 Hz, 1H, H-Ar), 7.00 (d, J ) 8.5 Hz,
1H, H-Ar), 6.53 (s, 1H, H-Ar), 4.29-4.14 (m, 8H, OCH2), 4.06 (s,
2H, COCH2CO), 4.01 (s, 2H, COCH2CO), 2.12-2.00 (m, 8H, CH2),
1.54-1.26 (m, 40H, CH2), 0.90-0.75 (m, 12H, CH3). 13C NMR
(75 MHz, CDCl3, 298 K, TMS): δ 161.3, 161.1, 160.8, 160.7, 159.6,
159.0, 157.6, 157.5, 157.1, 153.9, 137.0, 136.0, 133.9, 133.4, 132.0,
6376 J. Org. Chem. Vol. 73, No. 16, 2008

Hydrazide-Based Molecular Duplex Strands
was evaporated under reduced pressure, and the residue was
recrystallized from hot acetonitrile to give the product as a white
solid (0.42 g, 92%). Mp: 175-176 °C. 1H NMR (300 MHz, CDCl3,
298 K, TMS): δ 11.61-11.52 (br, 2H, H-N), 11.16-11.03 (br, 4H,
H-N), 10.87 (s, 2H, H-N), 9.12 (s, 1H, H-Ar), 8.23 (d, J ) 7.2 Hz,
2H, H-Ar), 7.46 (t, J ) 8.0 Hz, 2H, H-Ar), 7.10 (t, J ) 7.5 Hz,
2H, H-Ar), 6.99 (d, J ) 8.4 Hz, 2H, H-Ar), 4.24 (t, J ) 6.7 Hz,
4H, OCH2), 4.17 (t, J ) 7.0 Hz, 4H, OCH2), 3.97 (s, 4H,
COCH2CO), 2.15-1.99 (m, 8H, CH2), 1.54-1.26 (m, 40H, CH2),
0.86-0.83 (m, 12H, CH3). 13C NMR (75 MHz, DMSO-d6, 298 K,
TMS): δ 163.0, 162.9, 161.7, 160.6, 160.3, 156.5, 133.0, 130.6,
120.6, 120.4, 113.1, 112.9, 98.0, 69.7, 68.9, 31.2, 28.7, 28.6, 28.5,
28.3, 25.5, 22.0, 13.9. IR (KBr): ν ) 3316, 3208, 2926, 2858, 1626,
1466 cm-1. ESI MS: m/z 1113.98 [M - H]-. Anal. Calcd for
C60H90N8O12: C, 64.61; H, 8.13; N, 10.05. Found: C, 64.39; H,
8.19; N, 10.29.
1
FIGURE 10. Stacked partial H NMR spectra of (a) 1a and 2c, 298
Acknowledgment. We thank the National Natural Science
Foundation of China (20625206), National Basic Research
Program of China (2007CB808004, 2008CB617501), and
CMS-Y 200708 for financial support.
K, (b) 1a and 2c, 223 K, (c) 1c and 2c, 298 K, and (d) 1c and 2c, 223
K, 600 MHz, each 10 mM in CDCl3.
129.5, 128.5, 128.2, 126.1, 124.6, 121.2, 119.7, 118.9, 112.2, 111.8,
111.7, 107.4, 96.3, 70.4, 69.6, 52.4, 39.0, 31.8, 29.29, 29.25, 29.15,
28.84, 28.77, 26.1, 26.0, 22.6, 14.1. IR (KBr): ν ) 3347, 3223,
2926, 2858, 1627, 1461 cm-1. MS (MALDI-TOF): m/z 1187.7 [M
+ Na]+, 1203.6 [M + K]+. Anal. Calcd for C64H92N8O12: C, 65.96;
H, 7.96; N, 9.61. Found: C, 65.37; H, 8.08; N, 9.95.
Synthesis of 2b. To a solution of compound 8 (126 mg, 0.4
mmol) and compound 9 (347 mg, 0.4 mmol) in CH2Cl2 with cooling
in an ice-water bath was added EDC ·HCl (96 mg, 0.5 mmol).
The mixture was stirred at room temperature for 5 h. The solvent
Supporting Information Available: Copies of 1H NMR and
13C NMR spectra for new compounds. Stacked partial 1H NMR
spectra for the duplex strands at different temperatures and 2D
NOESY spectra. This material is available free of charge via
the Internet at http://pubs.acs.org.
JO801139P
J. Org. Chem. Vol. 73, No. 16, 2008 6377