Aggregation and columnar assembly of crescent oligoamides

Article abstract of DOI:10.1021/ol801410f

(Chemical Equation Presented) The aggregation and assembly of crescent oligoamides with two to six benzene residues are investigated. In chloroform, the pentamer and hexamer are found to associate into large aggregates. In the solid state, all oligomers e

Full text of DOI:10.1021/ol801410f

ORGANIC
LETTERS
2008
Vol. 10, No. 19
4339-4342
Aggregation and Columnar Assembly of
Crescent Oligoamides
Yunfeng Zhang,† Kazuhiro Yamato,‡ Kai Zhong,† Jin Zhu,† Jingen Deng,*,† and
Bing Gong*,‡
Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences,
Chengdu, 610041, China, and Department of Chemistry, UniVersity at Buffalo, The
State UniVersity of New York, Buffalo, New York 14260
bgong@chem.buffalo.edu
Received July 9, 2008
ABSTRACT
The aggregation and assembly of crescent oligoamides with two to six benzene residues are investigated. In chloroform, the pentamer and
hexamer are found to associate into large aggregates. In the solid state, all oligomers examined associate into columnar assemblies via
stacking interactions, as shown by X-ray diffraction data from single crystals and powder samples. The columnar assemblies of the pentamer
and hexamer should contain hydrophilic channels defined by the constituent oligomers.
Unnatural oligomers that fold into well-defined conforma-
tions, i.e., foldamers, have attracted intense interest during
the last ten years.1 The majority of foldamers, such as the
peptidomimetic R-aminoxy acid peptides,2 ꢀ-,3 γ-,4 and
δ-peptides,5 peptoids,6 and others with nonbiological back-
bones,7 has focused on folding into secondary, mostly
helical,9a structures. With many oligomers having well-
defined conformations now being available, the assembly of
foldamers into higher-order structures is attracting increasing
attention.8 We have developed a series of stably folded
aromatic oligoamides based on backbone-rigidification en-
forced by intramolecular three-center hydrogen bonds.9
Depending on its length, an oligoamide can adopt either a
† Chinese Academy of Sciences.
‡ The State University of New York.
(1) (a) Gellman, S. H. Acc. Chem. Res. 1998, 31, 173. (b) Hill, D. J.;
Mio, M. J.; Prince, R. B.; Hughes, T. S.; Moore, J. S. Chem. ReV. 2001,
101, 3893. (c) Gong, B. Chem.-Eur. J. 2001, 7, 4336. (d) Huc, I. Eur. J.
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E. R.; Gervay, J. J. Org. Chem. 1998, 63, 1074. (b) Hungerford, N. L.;
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Gellman, S. H. J. Am. Chem. Soc. 1996, 118, 13071. (b) Seebach, D.;
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Jaun, B. Chem.-Eur. J. 2002, 8, 573.
10.1021/ol801410f CCC: $40.75
Published on Web 09/11/2008
2008 American Chemical Society

crescent or a helical conformation. For example, short
oligomers consisting of less than seven meta-linked benzene
residues adopt a flat, crescent conformation.10 The flat shape
of the backbones is due to the planar arrangement enforced
by highly favorable11 intramolecular three-center H-bonds.
Results from our own studies indicate that the three-center
H-bonds we introduced are very robust and persist in both
nonpolar and polar media.12 Similar to the assembly of
disclike aromatic molecules with large, flat surfaces,13 these
stably folded crescent oligoamides, with their flat surfaces
of tunable areas, may also associate or aggregate based on
surface-surface stacking interactions, leading to assemblies
with anisotropic structures and properties. Herein, we
describe results from our initial investigation on the associa-
tion and assembly of a series of homologous crescent
oligoamides both in solution and in the solid state.
aggregates as shown by DLS measurements (Figure 1).
Consistent with the trend revealed by solubility difference
Figure 1. Results of dynamic light scattering measurements of (a)
2a (1 mM) and (b) 3a (1 mM), in chloroform at room temperature.
and changes of NMR line width, the aggregate formed by
hexamer 3a (around 700 nm, Figure 1b) is much larger than
that formed by pentamer 2a (around 90 nm, Figure 1a).
Interestingly, DLS studies also revealed a time dependence
for the aggregation of both 2a and 3a. Freshly prepared
solution of 2a or 3a in chloroform did not show any
detectable aggregation. In contrast, the size of the aggregate
formed by 2a or 3a kept increasing until about 1 h after
the solution was prepared. DLS measurements on the more
soluble 2b and 3a also revealed large aggregates.14 One
explanation of the observed time dependence in the aggrega-
tion of these oligomers may be the anisotropic interaction
of the molecules, which requires a proper orientation for
effective intermolecular association to take place. The
observed aggregation of oligoamides 2 and 3 is quite unusual
and contrasts the behavior of oligomers having aromatic
hydrocarbon backbones to which chloroform is a good
solvent that discourages stacking interactions.7b
The above results clearly demonstrated the association of
oligomers 2a and 3a in solution. To provide more insight into
the assembly of crescent oligoamides, we decided to probe the
assembly of these shape-persistent molecules in the solid state.
The crystal structures of short oligoamides 4-6 were previously
determined by us.10 On the basis of the X-ray data, examining
the packing of 4-6 revealed columnar assemblies formed by
all three oligomers (Figure 2).
It was observed that oligoamides 1a-3a showed a marked
solubility difference in chloroform. Tetramer 1a was readily
soluble, and 2a was soluble at up to 5 mM. In contrast,
hexamer 3a had a solubility of less than 2 mM. In addition,
the line width of the 1H NMR signals of these three oligomers
increased from tetramer 1a to pentamer 2a and to hexamer
3a.14 These results indicate that aggregation of the oligomers
is facilitated by stacking interaction that is proportional to
the surface area of the molecules.
The aggregation of oligomers 1a-3a in solution was then
examined by using dynamic light scattering (DLS). All three
oligomers appeared fully soluble when initially dissolved in
chloroform (1 mM) at room temperature. DLS could not
detect any aggregate in the solution of tetramer 1a. In
contrast, both pentamer 2a and hexamer 3a formed large
(8) (a) Mio, M. J.; Prince, R. B.; Moore, J. S.; Kuebel, C.; Martin, D. C.
J. Am. Chem. Soc. 2000, 122, 6134. (b) Raguse, T. L.; Lai, J. R.; LePlae,
P. R.; Gellman, S. H. Org. Lett. 2001, 3, 3963. (c) Lee, B. C.; Zuckermann,
R. N.; Dill, K. A. J. Am. Chem. Soc. 2005, 127, 10999. (d) Qiu, J. X;
Petersson, E. J.; Matthews, E. E.; Schepartz, A. J. Am. Chem. Soc. 2006,
128, 11338. (e) Bradford, V. J.; Iverson, B. L. J. Am. Chem. Soc. 2008,
130, 1517. (f) Petitjean, A.; Cuccia, L. A.; Schmutz, M.; Lehn, J. M. J.
Org. Chem. 2008, 73, 2481.
(9) (a) Sanford, A. R.; Gong, B. Curr. Org. Chem. 2003, 7, 1649. (b)
Gong, B. Acc. Chem. Res. 2008,ASAP article. Web Release Date: 07-May-
2008.
The column formed by dimer 4 consists of molecules that
are stacked in a parallel, nearly eclipsed fashion, with the
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Org. Lett., Vol. 10, No. 19, 2008

2 and 3 that bear short alkyl side chains have failed to yield
single crystals amenable to X-ray analysis, the assembly and
packing of 2b and 3b in the solid state were investigated
using other techniques.
The X-ray powder diffraction patterns of the solid sample
of 2b directly prepared from solution by evaporation of
solvent (CH2Cl2) failed to indicate large-scale organization.14
Oligomer 2b was then thermally treated under nitrogen by
being placed between two glass plates and heated to become
an isotropic liquid with an oil bath (150-200 °C). Stress
was then applied to the molten sample by slightly pulling
the upper glass plate along the plane of the glass plate
unidirectionaly.15 The treated sample was rapidly cooled in
liquid nitrogen and was subsequently allowed to warm to
room temperature. The XRD diffraction pattern indicates a
highly ordered phase (Figure 3a). The presence of an
Figure 2. Side and top views of columnar assemblies observed
in the solid state structures of (a) dimer 4, (b) trimer 5, and (c)
tetramer 6.
plane of each molecule and that of the column being nearly
perpendicular. In the columns formed by trimer 5 and
tetramer 6, the molecules are also parallelly stacked, with
angles of ∼45° and ∼30°, respectively, between the long
axes of the molecules and those of the corresponding
columns. The distances between the planes of adjacent
molecules in all columns are between 3.5 and 3.6 Å,
indicating that aromatic stacking interactions are responsible
for associating the molecules into the columns. The columns
further assemble via van der Waals interaction between the
numerous C-H bonds from aromatic rings and the alkyl side
chains.
The packing of 4-6 suggests that forming columnar
assemblies may be a common feature for these crescent
oligoamides in the solid state. Thus, higher homologues of
4-6, such as oligomers 2 and 3, with their larger surface
areas, not only aggregate in solution as shown by 2a and 3a
but also may associate into columnar assemblies in the solid
state. Columnar assemblies of pentamer 2 and hexamer 3
are particularly interesting because with their increasingly
enclosed cavities the assembled structures should have
hydrophilic channels running down the columns. Since
repeated efforts to grow single crystals of the analogues of
Figure 3. (a) Diffractogram of the thermally treated solid sample
of pentamer 2b. (b) Schematic drawing of the columnar packing
of 2b and the hexagonal lattice. The hexagonal lattice parameter a
is 28.9 Å. This cartoon does not imply the actual stacking axis
geometry which is currently unknown.
overwhelmingly dominant peak at 25 Å and the paucity of
other peaks in the diffractogram of 2b are characteristic of
columnar assemblies formed by disclike molecules.16 The
ratios of the d-spacings of the dominant peak at 25 Å, along
with the weaker peaks at 14.77 and 12.47 Å (1:1/ꢀ3:0.5),
are consistent with those from a two-dimensional hexagonal
lattice (Colhd),16 based on which a lattice parameter of a )
28.9 Å is obtained (Figure 3b). Parameter a is the diameter
of the column which is consistent with the molecular
dimension of 2b. In addition, the broad maximum at ∼4.2
Å is often observed with columnar discotic liquid crystals
and can be assigned to the distance between the packed side
chains of 2b. The presence of a distinct peak at 3.48 Å can
(10) (a) Zhu, J.; Parra, R. D.; Zeng, H.; Skrzypczak-Jankun, E.; Zeng,
X. C.; Gong, B. J. Am. Chem. Soc. 2000, 122, 4219. (b) Gong, B.; Zeng,
H. Q.; Zhu, J.; Yuan, L. H.; Han, Y. H.; Cheng, S. Z.; Furukawa, M.; Parra,
R. D.; Kovalevsky, A. Y.; Mills, J. L.; Skrzypczak-Jankun, E.; Martinovic,
S.; Smith, R. D.; Zheng, C.; Szyperski, T.; Zeng, X. C. Proc. Natl. Acad.
Sci. U.S.A. 2002, 99, 11583. (c) Yuan, L, H.; Zeng, H. Q.; Yamato, K.;
Sanford, A. R.; Feng, W.; Atreya, H. S.; Sukumaran, D. K.; Szyperski, T.;
Gong, B. J. Am. Chem. Soc. 2004, 126, 16528.
(11) Rozas, I.; Alkorta, I.; Elguero, J. J. Phys. Chem. A 1998, 102, 9925.
(12) Parra, R. D.; Zeng, H. Q.; Zhu, J.; Zheng, C.; Zeng, X. C.; Gong,
B. Chem.-Eur. J. 2001, 7, 4352.
(13) Kumar, S. Chem. Soc. ReV. 2006, 35, 83.
(14) Please see Supporting Information for more details.
Org. Lett., Vol. 10, No. 19, 2008
4341

be attributed to the interplanar reflections between the flat
backbones of the molecules, which suggests relatively strong
stacking interactions between the backbones of the molecules
in the columns and indicates the existence of periodicity
along the columns.
and have a narrow distribution of diameters that are between
0.3 to 0.4 µm (average 0.35 µm). The SEM image provided
additional evidence that is consistent with the highly aniso-
tropic nature of the assembly formed by 2b.
In summary, oligoamides 2a and 3a showed an obvious
tendency to self-assemble in solution, as demonstrated by
solubility difference, changes of NMR line width, and the
formation of nanosized aggregates. The aggregation of these
two oligomers in solution is presumably due to stacking
interactions promoted by the flat, well-defined oligoamide
backbones. However, the fact that aggregation was observed
in chloroform which normally discourages aromatic stacking
interactions suggests the possibility of a stacking mechanism
unique to this and analogous systems. In the solid state, the
columnar packing of short crescent oligoamides 4-6 is
revealed by examining X-ray data obtained from the corre-
sponding single crystals. The columnar and hexagonal
packing of pentamer 2b is clearly indicated by X-ray
diffraction patterns and SEM image. The diffraction patterns
of the solid sample of hexamer 3b share the same general
features shown by those of 2b, suggesting that 3b also packs
into columns. These initial results have demonstrated the
strong association and anisotropic, columnar packing of
crescent oligoamides, which have provided the basis for the
subsequent study and elucidation of the supramolecular
assemblies of these molecules. With their persistent flat shape
and easily modifiable side chains that allow the introduction
of more directional intermolecular interactions such as
H-bonding, crescent oligoamides offer a set of readily
available and tunable nanosized building blocks that should
lead to the creation of new nanoporous structures with
uniform, hydrophilic channels. The corresponding objective
is being pursued and will be reported in due course.
Similarly, XRD measurements of the powder sample of
hexamer 3b prepared by removing solvent from solution did
not reveal any ordered phase. In contrast, XRD measurements
of thermally treated solid sample of 3b prepared in the same
way as that used for 2b revealed diffraction patterns that
share the general features (see Supporting Information).14
An overwhelmingly dominant peak at ∼28 Å and the dearth
of other prominent peaks are associated with the diffracto-
grams of thermally treated 3b,14 suggesting that molecules
of 3b also stack into columnar structures. A peak at ∼3.5 Å
corresponding to interplanar reflections between the flat
backbones of 3b can be observed in each case. Thus, the
diffractograms of 3b strongly suggest that 3b also forms
columnar structures in the solid state. Unfortunately, the
obtained diffractograms of 3b do not allow the peaks to be
properly indexed.
The XRD results suggest that, similar to the assembly of
their shorter homologues 4-6 and that of discotic liquid
crystals, the molecules in the thermally treated solids of 2b
and 3b are ordered into columns that further pack on a
hexagonal lattice.
Acknowledgment. Grateful acknowledgment is made to
the National Nature Science Foundation of China (grant No.
20428202 to BG and JGD) and the NSF (CHE-0701540 to
BG) for support.
1
Supporting Information Available: H NMR spectra,
diffractograms, SEM images, and analytical data. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Figure 4. Scanning electron micrograph of the thermally treated
sample of 2b.
OL801410F
(15) The sample of 2b was similarly treated but without being subjected
to such stress gave very similar diffraction patterns that can be indexed to
a hexagonal lattice (see Supporting Information).
(16) Prasad, S. K.; Rao, D. S. S.; Chandrasekhar, S.; Kumar, S. Mol.
Cryst. Liq. Cryst. 2003, 396, 121.
Figure 4 shows the SEM image of the thermally treated
sample of 2b. Fibers with lengths over several micrometers
were observed.14 In addition, these fibers seem to be rigid
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