A hydrogen bonding motif for forming extended assemblies

Article abstract of DOI:10.1039/b924008j

Oligoamide strands containing tertiary amide groups were found to share a basic structural motif that promotes the formation of H-bonded, chain- or tape-like supramolecular assemblies.

Full text of DOI:10.1039/b924008j

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A hydrogen bonding motif for forming extended assembliesw
Jiahui Zhang,ab Xiangxiang Wu,ab Kazuhiro Yamato,c Futao Liu,ab Tianyi Su,ab
Chong Zheng,d Lan He*ab and Bing Gong*abc
Received (in Austin, TX, USA) 16th November 2009, Accepted 30th November 2009
First published as an Advance Article on the web 12th January 2010
DOI: 10.1039/b924008j
Oligoamide strands containing tertiary amide groups were found
to share a basic structural motif that promotes the formation of
H-bonded, chain- or tape-like supramolecular assemblies.
design takes advantage of readily available benzene derivatives
that offer multiple sites for further modification. However,
based on known solid-state structures of N-Me tertiary
anilides,7 the tertiary amide groups of 4–6 are not likely to
be coplanar with the benzene rings to which they are attached
and thus may not be properly oriented with the NH groups,
which may prevent dimerization from happening. Another
possibility is that, as the number of intermolecular H-bonds
increases, the entropic and particularly enthalpic advantages
of dimerization8 might overcome the unfavorable conforma-
tional preference caused by the tertiary amide moieties,
leading to discrete H-bonded duplexes like those consisting
of 1–3. Herein we report results from studying the association
of oligoamides 4–6. Instead of forming dimers, these oligoamide
strands were found to associate via H-bonding into extended
H-bonded chains or tapes. It has turned out that the
N-Me groups have resulted in a structural motif with a
conformational preference that promotes the formation of
extended, rather than discrete, assemblies.
The hydrogen bond, with its superb strength and predictable
directionality, has been widely adopted in developing various
self-assembling structures.1,2 An effective strategy for specifying
intermolecular association involves the encoding of specificity
and tuning of binding strength.3 We have developed a series
of H-bonded duplexes consisting of oligoamide strands as
sequence-tunable association units.4,5 An oligoamide, such as
1, 2 or 3, has an edge bearing a linear array (sequence) of
properly oriented H-bond donors and acceptors. With their
benzamido NH groups being intramolecularly H-bonded and
thus being prevented from engaging in intermolecular
H-bonding, and the self-complementary arrangement of the
remaining amide H and O atoms, each of 1–3 has one
H-bonding edge that ensures the dimerization of these
molecules via two, four, and six intermolecular H-bonds.5 By
recombining amide H and O atoms, a variety of analogous
duplexes were designed and formed sequence-specifically.
These duplexes possess superb sequence-specificity and have
served as non-covalent association units for constructing
supramolecular AB diblock copolymers,6a,b as templates
for inducing the formation of b-sheets,6c and for directing
chemical reactions.6d–f
Amides 4–6 were synthesized from the commercially
available sarcosine and 3-nitrobenzoic acid based on similar
procedures we described before.6a–e Characterization of 4–6
1
using H and 13C NMR, as well as mass spectrometry (ESI)
gave satisfactory analytical results.w
The aggregation of 4 was examined by H NMR dilution
1
studies in CDCl3. The signal of the secondary amide proton of
4 showed concentration-dependent shift. Similar 1H NMR
study on 5a also showed concentration-dependent shifts of
1
both amide proton signals. Attempts to record the H NMR
spectra of compound 6a in CDCl3 was unsuccessful due to the
limited solubility of this compound. Nevertheless, results
based on 4 and 5a indicated the involvement of the amide H
atoms of both compounds in H-bonding interactions, suggesting
that these amides might be undergoing the expected H-bond-
mediated dimerization.
As an initial attempt to include readily available building
blocks into the system, compounds 4–6, which share the same
backbone linkages as those of 1–3, were designed.w Such a
1
However, in contrast to the well-resolved, sharp H NMR
resonances of 1–3 recorded in CDCl3,4,5 the spectra of 4, 5a, 5b
and 6b, showed increasingly broad lines.w The line-broadening
in CDCl3 is even more obvious when comparing to those
of the spectra recorded in DMSO-d6.w This observation
suggested that these molecules, although undergoing H-bonding
interactions, might not be forming the H-bonded dimers that
are associated with 1, 2 and 3. Instead, the observed line-
broadening of their NMR signals suggests that they either
associated into oligomeric or polymeric aggregates, and/or
existed as multiple species undergoing rapid exchange.
a College of Chemistry, Beijing Normal University, Beijing 100875,
China
b State Key Laboratory of Applied Organic Chemistry,
Lanzhou University, Lanzhou 730000, China.
E-mail: helan1961@yahoo.com.cn; Tel: (+86) 10 5880 2076
c Department of Chemistry, University at Buffalo, State University of
New York, Buffalo, NY 14260, USA. E-mail: bgong@buffalo.edu;
Fax: (+1) 716 645 6963; Tel: (+1) 716 645 4307
d Department of Chemistry and Biochemistry, Northern Illinois
University, DeKalb, IL 60115, USA. E-mail: czheng@niu.edu
w Electronic supplementary information (ESI) available: Experimental
procedures; NMR spectra; mass spectra. CCDC 745618 and 745619.
For ESI and crystallographic data in CIF or other electronic format
see DOI: 10.1039/b924008j
Results from vapor pressure osmometry (VPO, polystyrene
standards) revealed the aggregation of 4 and 5a in chloroform.
Compound 4 had aggregation numbers of 2.1 ꢀ 0.06 at 20 mM,
ꢁc
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Fig. 1 Results of dynamic light scattering measurements of (a) 4
(4 mM), (b) 5a (4 mM), (c) 5b (1 mM) and (d) 6b (1 mM) in chloroform
at room temperature.
and 2.4 ꢀ 0.06 at 100 mM, suggesting that 4 existed mainly as
dimers in solution. Amide 5a had aggregation numbers of
3.1 ꢀ 0.33 at 20 mM, and 4.4 ꢀ 0.18 at 100 mM, which
indicated that 5a aggregated beyond the dimerization stage.
Since VPO offers a macroscopic view of average aggregation
degree, the likely presence of large aggregates formed by 4 and
5a was probed using dynamic light scattering (DLS). While
aggregates with size between 1 to 2 nm were detected for 4
(Fig. 1(a)), compound 5a was found to form large aggregates
with an average size around 100 nm in chloroform (Fig. 1(b)).
Due to the limited solubility of 6a, compound 6b was prepared
and examined with DLS in chloroform, which revealed
aggregates with an average size of B240 nm (Fig. 1(d)).
Compound 5b, which has the same tail of 6b but shares the
rest of its structure with compound 5a, aggregates with an
average size of 160 nm (Fig. 1(c)).
Fig. 2 (a) The top and side views of the X-ray structure of 4. (b) The
top and side views of the ladder-like chain consisting of H-bonded
molecules of 4 (four molecules shown).
The two-dimensional sheets further pack via van der Waals
interactions and weak C–Hꢃ ꢃ ꢃO H-bonds between the methyl
groups, the aromatic H atoms and amide O atoms, into a
three-dimensional layered structure.
Single crystals of 5a were grown from a solution in methanol–
water (30 : 1, v/v). The X-ray structure of 5a indicates that,
each of the two benzene residues adopts nearly the same
conformation as that revealed by the crystal structure of 4,
in which the secondary amide NH group and the tertiary
amide CQO group are nearly orthogonal to each other. The
extended conformation of 5a can be regarded as being derived
by connecting two such aromatic residues via a glycine linker
(Fig. 3(a)), in which the two secondary amide NH groups are
parallel to each other and point to the same direction while the
two tertiary amide CQO groups point to an almost orthogonal
direction. Because of such a conformation, the molecules of 5a
are incapable of dimerizing. Instead, they align antiparallel in
a side-by-side way, packing into an extended H-bonded tape in
the solid state by forming two H-bonds between two adjacent
molecules (Fig. 3(b), top view). Reflecting the orthogonal
orientations of the NH and the CQO groups, the molecules
of 5a in the H-bonded tape are arranged in a zigzagged way as
viewed along the long axis of the individual molecules
(Fig. 3(b), side view). Like 4, compound 5a also exhibits a
structural hierarchy in the solid-state. The H-bonded tapes
align side-by-side in the plane defined by themselves into
extended 2D layers that further stack into a layered solid state
structure.
The VPO and DLS results indicate that compounds 5a, 5b
and 6b indeed formed extended, rather than discrete, assemblies.
However, the aggregation of 4 was less clear. It may exist
predominantly as dimers, or as a mixture of rapidly exchanging
monomer, dimer and higher oligomers.
Based on the VPO result, nonlinear regression analysis9 of
the NMR data yielded a dimerization constant of B7.0 Mꢂ1
for compound 4. Such a dimerization constant is much smaller
than that of the doubly H-bonded dimer (Kdimer = 25–50 Mꢂ1
)
of 1,4,5a–c which implied that the H-bond-mediated association
of 4 might be different from that of 1.
X-Ray quality crystals of compounds 4 and 5a were
obtained, which led to the determination of the corresponding
solid-state structures.z Single crystals of 4 were obtained from
a solution in chloroform–methanol by slow cooling from
70 1C. As shown in Fig. 2(a), the two amide groups of 4 are
not coplanar with the benzenoid ring: the acetamido group has
a dihedral angle of 31.21 with the plane of the benzenoid ring,
and the tertiary amide group has a dihedral angle of 53.31 with
the plane of the benzenoid ring. The tertiary amide CQO
group and the secondary amide NH group are not aligned in
the same direction, which prevents 4 from dimerizing via
H-bonding. Instead, each molecule of 4 forms two H-bonds
with two adjacent molecules. As a result, a H-bonded,
ladder-like chain is resulted (Fig. 2(b)). The next level of
the solid-state structure involves the parallel alignment of
the ladder-like chains into extended two-dimensional sheets.
The fact that a very similar conformation is associated with
the aromatic residues of both 4 and 5a suggests that this is a
reliable structural motif. The persistency of this motif in
solution is consistent with the observed weak intermolecular
H-bonding interaction of 4. While 1–3 associate via H-bonds
into discrete dimers, compounds 4–6 could only form extended
assemblies via one or two H-bonds between two adjacent
molecules.
Although attempts to probe the intermolecular association
of 5b in solution by using two-dimensional (NOESY) NMR
ꢁc
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V = 2150.29(9) A3, Z = 4, T = 296(2) K, m(Mo-Ka) = 0.093 mmꢂ1
,
10982 reflections measured (4942 unique, Rint = 0.0230). R1 [I 4 2s(I)] =
0.0527, wR2 = 0.1657 (F2, all data).
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top and side views of the H-bonded tape formed from H-bonded
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hydrogens are shown.
were complicated due to overlap of signals,w the NOESY
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tail alignment of the molecules in solution.w
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In summary, oligoamide strands consisting of benzene
residues bearing meta-substituted secondary and tertiary
amide moieties were found to carry orthogonally oriented
H-bond donors and acceptors. These extended strands associate
via intermolecular H-bonding interactions into extended
chains and tapes. The persistency of the basic structural motif
was demonstrated by solid-state structures and also supported
by NMR, VPO and DLS studies. The revealed structural motif
should be valuable for the design of extended structures
such as sheet-like supramolecular assemblies. For example,
covalently linking the backbones of 4–6 and their higher
homologs may lead to unnatural, sheet-like structures consisting
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This work was supported by the Changjiang Scholar
Program and the Cultivation Fund of the Key Scientific and
Technical Innovation Project, Ministry of Education of China
Grant 706009 (to BG), the NSFC Grant 20772012, RFDP
Grant 20070027038 and KNDCDP Grant 2009ZX09502-008
(to LH), and National Science Foundation Grant CHE-0314577
(to BG). The Beijing Municipal Commission of Education
and the Beijing New Medical Discipline Based Group
(XK100270569).
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Notes and references
8 A. T. ten Cate and R. P. Sijbesma, Macromol. Rapid Commun.,
2002, 23, 1094.
z Crystal data: for 4: C11H14N2O2, M = 206.24, monoclinic, space
b = 96.382(5)1, V = 546.9(6) A3, Z = 2, T = 293(2) K, m(Mo-Ka) =
0.088 mmꢂ1, 3503 reflections measured (2372 unique, Rint = 0.0226).
R1 [I 4 2s(I)] = 0.0739, wR2 = 0.1666 (F2, all data). 5a: C20H22N4O4,
group P21,
a = 6.545(5), b = 9.091(5), c = 9.249(5) A,
9 C. S. Wilcox, in Frontiers in Supramolecular Organic Chemistry and
Photochemistry, ed. H.-J. Schneider and H. Durr, VCH, New York,
1991. The dimerization constants were obtained by fitting the NMR
data into a modified dimerization equation with the program
Kaleidagraph on a Macintosh computer.
M
=
382.42,
monoclinic,
space
group
P21/c,
a = 13.7983(3), b = 7.5207(2), c = 21.2520(5) A, b = 102.834(2)1,
ꢁc
This journal is The Royal Society of Chemistry 2010
1064 | Chem. Commun., 2010, 46, 1062–1064