Programming the internal structure and stability of helical pores self-assembled from dendritic dipeptides via the protective groups of the peptide

Article abstract of DOI:10.1021/ja056313h

The synthesis of dendritic dipeptides (4-3,4-3,5) 12G2-CH2-X-L-Tyr-L-Ala- OMe with X = Boc, Moc, and Ac; their self-assembly in bulk and in solution; and the structural and retrostructural analysis of their supramolecular helical porous assemblies are rep

Full text of DOI:10.1021/ja056313h

Published on Web 11/23/2005
Programming the Internal Structure and Stability of Helical
Pores Self-Assembled from Dendritic Dipeptides via the
Protective Groups of the Peptide
Virgil Percec,*,† Andre´s E. Dulcey,† Mihai Peterca,‡ Monica Ilies,†
Monika J. Sienkowska,† and Paul A. Heiney‡
Contribution from the Roy & Diana Vagelos Laboratories, Department of Chemistry, UniVersity
of PennsylVania, Philadelphia, PennsylVania 19104-6323, and Department of Physics and
Astronomy, UniVersity of PennsylVania, Philadelphia, PennsylVania 19104-6396
Received September 17, 2005; E-mail: percec@sas.upenn.edu
Abstract: The synthesis of dendritic dipeptides (4-3,4-3,5)12G2-CH2-X-L-Tyr-L-Ala-OMe with X ) Boc,
Moc, and Ac; their self-assembly in bulk and in solution; and the structural and retrostructural analysis of
their supramolecular helical porous assemblies are reported. The dimensions, structure, internal order,
thermal stability of the supramolecular helical pores, and conformations of the dendron and supramolecular
dendrimer are programmed by the nature of the protective groups of the dipeptide. The ability of the
protective groups to program the structure of the helical pore reveals the simplest design strategy that
complements the more complex strategies based on the architecture of the dendron, the stereochemistry,
and the structure of the dipeptide.
Introduction
successful. Recently, we reported that amphiphilic dendrons
functionalized at their apex with a dipeptide create “dendritic
Natural pore-forming proteins form the channels that cells
use to communicate with one another and the outside world.1
They also form the coats of viruses,2 and some have pathogenic3
and antibiotic4 activity. Remodeled porous proteins are used in
synthetic systems, in the encapsulation of molecules,5 and in
molecular sensing.6 Synthetic strategies for obtaining porous
or tubular supramolecular assemblies have been elaborated.7
However, with few exceptions,8 attempts to create synthetic
pores capable of assembling into periodically ordered assemblies
that are stable both as solids and in solution have yet to be
dipeptides” that self-assemble both in solution and in the solid
state into supramolecular helical porous structures.9 This self-
assembly process is sufficiently robust to tolerate a range of
modifications9,10 to the structure of the peptide and dendron,
and preliminary data showed that these synthetic pores are
functional.9a Therefore, it is expected that the elucidation of the
principles of this self-assembly process will allow the design
of a variety of biologically inspired systems with functional
properties arising from their porous structure. The structure of
the pore is determined by the architecture of the dendron,9a,10a
the peptide,9a and the stereochemistry9a,10b of the dipeptide. Here,
we report that the protective groups of the dipeptide program
both the internal structure and the thermal stability of the helical
pores self-assembled from dendritic dipeptides. This unexpected
result provides the simplest and one of the most powerful
architectural tools available for programming the structure and
stability of porous protein mimics self-assembled from dendritic
dipeptides.9
* To whom correspondence should be addressed.
† Department of Chemistry.
‡ Department of Physics and Astronomy.
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17902
J. AM. CHEM. SOC. 2005, 127, 17902-17909
10.1021/ja056313h CCC: $30.25 © 2005 American Chemical Society

Helical Pores in Self-Assembled Dendritic Dipeptides
A R T I C L E S
Scheme 1. Synthesis of the Dendritic Dipeptides (4-3,4-3,5)12G2-CH2-X-L-Tyr-L-Ala-OMe, X ) Boc, Moc, Ac
Results and Discussion
Structural and Retrostructural Analysis in the Solid State.
A combination of differential scanning calorimetry (DSC)
together with small-and wide-angle X-ray diffraction (XRD)
experiments recorded during heating and cooling on powder
and oriented fibers, electron density maps, simulations of the
XRD data, and molecular modeling was used to perform the
structural and retrostructural analysis of the supramolecular
structures self-assembled from the dendritic dipeptides in the
bulk.9a,13 Phase transitions were determined by DSC, and the
structures of the periodic arrays were assigned by XRD. Figure
1 shows the DSC traces of the compounds and summarizes the
periodic lattices in which the supramolecular structures self-
organize.
Synthesis of Dendritic Dipeptides (4-3,4-3,5)12G2-CH2-
X-L-Tyr-L-Ala-OMe with X ) Boc, Moc, and Ac. The
dipeptides Boc-L-Tyr-L-Ala-OMe, Moc-L-Tyr-L-Ala-OMe,
and Ac-L-Tyr-L-Ala-OMe were synthesized from Boc, Moc,
and Ac N-protected L-Tyr with the methyl ester of L-Ala
hydrochloride in the presence of 2-chloro-4,6-dimethoxy-1,3,5-
triazene (CDMT)9a,11/N-methyl morpholine (NMM) in EtOAc
(Scheme 1) in 70-90% yield after purification by column
chromatography (SiO2/gradient 2-4% MeOH in CHCl3). The
dendritic dipeptides were obtained by the Mitsunobu etherifi-
cation12 of the hydroxyphenyl group of the dipeptides with (4-
3,4-3,5)12G2-CH2OH.5,9a,13c Purities higher than 99% (HPLC)
were obtained in 41-45% yield after purification by flash
column chromatography (SiO2/gradient 2-4% MeOH in CHCl3).
All dendritic dipeptides self-assemble into porous supramo-
lecular columns that self-organize into periodic hexagonal
columnar arrays. A brief inspection of Figure 1 indicates that
three different kind of columns, one with liquidlike intra-
columnar disorder (Φh), one with short-range intracolumnar
helical order, and one with long-range13e,g intracolumnar helical
(11) Kronin, J. S.; Ginah, F. O.; Murray, A. R.; Copp, J. D. Synth. Commun.
1996, 26, 3491-3494.
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Am. Chem. Soc. 1998, 120, 11061-11070. (b) Percec, V.; Cho, W.-D.;
Ungar, G. J. Am. Chem. Soc. 2000, 122, 10273-10281. (c) Percec, V.;
Cho, W.-D.; Ungar, G.; Yeardley, D. J. P. J. Am. Chem. Soc. 2001, 123,
1302-1315. (d) Percec, V.; Mitchell, C. M.; Cho, W.-D.; Uchida, S.;
Glodde, M.; Ungar, G.; Zeng, X.; Liu, Y.; Balagurusamy, V. S. K.; Heiney,
P. A. J. Am. Chem. Soc. 2004, 126, 6078-6094. (e) Zeng, X.; Ungar, G.;
Liu, Y.; Percec, V.; Dulcey, A. E.; Hobbs, J. K. Nature 2004, 428, 157-
160. (f) Bernal, D. J.; Fankuchen, I. Nature 1937, 139, 923-925. (g) Kwon,
Y. K.; Chvalun, S. N.; Blackwell, J.; Percec, V.; Heck, J. A. Macromol-
ecules 1995, 28, 1552-1558. (h) Kwon, Y. K.; Chvalun, S. N.; Schneider,
A.-I.; Blackwell, J.; Percec, V.; Heck, J. A. Macromolecules 1994, 27,
6129-6132. (i) Percec, V.; Rudick, J. G.; Peterca, M.; Wagner, M.; Obata,
M.; Mitchell, C. M.; Cho, W.-D.; Balagurusamy, V. S. K.; Heiney, P. A.
J. Am. Chem. Soc. 2005, 127, 15257-15264.
io
order (both labeled Φh ), are self-assembled from these dendritic
dipeptides. The hexagonal columnar arrays with intracolumnar
order differ from conventional hexagonal columnar liquid
crystals (Φh) that have intracolumnar liquidlike disorder and
from 3-dimensional crystals in that no long-range intercolumnar
order is available. However, these arrays are expected to be
precursors to hexagonal columnar crystals. Examples of intra-
columnar order in biological13f and synthetic13g-i hexagonal
columnar assemblies are known. A detailed discussion of these
9
J. AM. CHEM. SOC. VOL. 127, NO. 50, 2005 17903

A R T I C L E S
Percec et al.
Table 1. Thermal Transitions of (4-3,4-3,5)12G2-CH2-X-L-Tyr-L-Ala-OMe, X ) Boc, Moc, Ac
thermal transitions (
°
C) and corresponding enthalpy changes (kcal/mol)a
X
heating
cooling
Boc
Moc
Ac
Φh,gb 57 Φhc 96 (5.8) i
i 94 (5.8) Φh 53 Φh,g
io
Φh,gio e 55 Φhio d 80 (-5.2) Φhio 109 (1.0) Φhio 118 (12.0) i
Φh,gio 57 Φhio 120 (0.4) Φhio 128 (7.5) i
i 112 (6.4) Φh 78 (1.4) Φhio 47 Φh,g
i 122 (1.7) Φh 119 (1.7) Φhio 51 Φh,g
io
a Thermal transitions (°C) and enthalpy changes (kcal/mol) were determined by DSC (10 °C/min). Data from the second heating and cooling scans are
b
io
shown. Φh,g ) glassy state of the hexagonal columnar lattice; c Φh ) p6mm hexagonal columnar lattice; d Φh ) columnar hexagonal lattice with
e
io
intracolumnar order; Φh,g ) glassy state of the hexagonal columnar lattice with intracolumnar order.
hexagonal columnar lattices by 24 and 32 °C, respectively. All
of these results are summarized in Table 1.
Even more remarkable is the effect of the protective group
on the intensity of the d spacing of the hexagonal columnar
lattices self-organized from these supramolecular columns
(Figure 2a,b). The porous structure of these columns and their
intracolumnar model were demonstrated by a combination of
transmission electron microscopy and electron diffraction
experiments combined with electron density maps calculated
from the XRD data.9a Dpore is calculated by the simulation of
the XRD peak positions and intensities using the electron density
of the dendritic dipeptide and considering a three-phase intra-
columnar model consisting of aliphatic, aromatic, and peptide
regions in addition to the hollow center of the column. Details
of this calculation were reported previously.9a The application
of this method to more complex porous structures will be
reported elsewhere. Therefore, the relative intensities of the (10),
(11), (20), and (21) d spacings provide an immediate indication
of the pore diameter (Dpore).9a,10 Previously, we reported that,
in the bulk, Dpore for Boc-protected dendritic dipeptides is almost
constant below the glass transition temperature (Tg) of the
supramolecular structure and is strongly dependent on temper-
ature above Tg.10b The dependences of the column diameter
(Dcol) and the pore diameter (Dpore) on temperature are plotted
for all protective groups in Figure 2c,d. The data reported in
Figure 2c,d provide two additional important results. The
structure of the protective group provides a powerful architec-
tural parameter that programs Dpore. This result is not unex-
pected. However, the fact that Boc provides a larger Dpore value
than Moc and Ac could not be predicted. In fact, we expected
a lower Dpore value for the structure self-assembled from the
Boc-protected dendritic dipeptide. In addition, in the case of
Boc, Dpore is stable and temperature-independent below Tg,
whereas in the cases of Moc and Ac, Dpore is stable for the entire
range of temperatures of the Φhio phase. This second unpredict-
able result is very rewarding because it provides a new
mechanism to stabilize the porous structure not only in bulk
but also in solution. These results are summarized in Table 2.
Table 2 also contains the number of dendrons that form the
stratum of the supramolecular columns (µ)9a,13a-d and the
projection of the solid angle (R′)13b,14 of the dendron from the
supramolecular column. The role of µ and R′ in the ability of
the protective groups to program the structure of the pore is
discussed later.
Figure 1. DSC traces (second heating and cooling scans, both at 10 °C/
min) of (4-3,4-3,5)12G2-CH2-X-L-Tyr-L-Ala-OMe: (a) X ) Boc, (b)
X ) Moc, and (c) X ) Ac. Transition temperatures are indicated in degrees
Celsius, and the corresponding enthalpy changes (in parantheses) are in
io
kilocalories per mole. Φh ) p6mm hexagonal columnar 2-D lattice, Φh
)
columnar hexagonal lattice with intracolumnar order, Φh,gio ) glassy state
of the hexagonal columnar lattice, Φh,g ) glassy state of the hexagonal
io
columnar lattice with intracolumnar order.
intracolumnar ordered structures and their comparison with
crystals and liquid crystals will be presented elsewhere. The
Boc protective group provides columns that self-organize into
hexagonal columnar (Φh) lattices. Below the glass transition,
their dynamic short-range helical order is frozen, and therefore,
this order can be observed by XRD.9a The Moc and Ac
protective groups mediate self-assembly below 109 and 120 °C,
respectively, into supramolecular columns with long-range
intracolumnar helical order that self-assemble into hexagonal
columnar periodic arrays with intramolecular order (Φhio).
Above these temperatures, both Moc and Ac form columns with
different long-range intracolumnar order (Supporting Informa-
tion). Upon cooling from the isotropic state, Moc and Ac
dendritic dipeptides form a monotropic Φh phase similar to that
of Boc dendritic dipeptide. In the case of Moc, the Φh structure
transforms into Φhio upon cooling at 78 °C. However, because
of the close proximity of this exotherm to the glass transition
temperature (Tg), the formation of the Φhio phase is completed
upon heating above Tg via the exotherm at 80 °C. In the case
of Ac, the monotropic Φh structure transforms into Φhio at 119
°C. In addition to the creation of supramolecular columns with
enhanced intracolumnar order, the transition from Boc to Moc
and to Ac protective groups increases the stability of the
Figure 3 shows small- and wide-angle XRD data obtained
from the aligned fibers of the dendritic dipeptides. As shown
by the X shapes of the i and h diffractions (Figure 3), all
supramolecular columns are helical. However, regardless of
temperature, Boc induces a short-range intracolumnar helical
(14) Ungar, G.; Percec, V.; Holerca, M. N.; Johansson, G.; Heck, J. A. Chem.
Eur. J. 2000, 6, 1258-1266.
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Helical Pores in Self-Assembled Dendritic Dipeptides
A R T I C L E S
Figure 2. Small-angle X-ray diffraction plots at (a) 25 and (b) 75 °C for the supramolecular structures self-assembled from (4-3,4-3,5)12G2-CH2-X-
L-Tyr-L-Ala-OMe, X ) Boc, Moc, Ac. Dependence of the (c) column (Dcol) and (d) pore (Dpore) diameters on temperature.
Table 2. (4-3,4-3,5)12G2-CH2-X-L-Tyr-L-Ala-OMe Structural and Retrostructural Analysis by XRD
µd
T
d10a (Å)
(A10b a.u.)
d11a (Å)
(A11b a.u.)
d20a (Å)
(A20b a.u.)
d21a (Å)
(A21b a.u.)
Dcol
(Å)
Dpore
(Å)
Fc
(g/cm3)
(dendrons/
stratum)
R′ e
(deg)
X
(
°C)
Boc
20
80
25
68.1
(43.5)
65.6
(44.6)
64.4
(55.3)
65.2
(55.9)
61.5
39.1
(25.6)
37.7
(26.0)
37.2
(20.9)
37.5
(20.5)
35.4
33.9
(24.9)
32.7
(24.1)
32.2
(16.7)
32.4
(16.5)
30.7
26.2
(5.9)
24.7
(5.4)
24.4
(7.0)
24.6
(7.0)
23.2
(7.4)
23.3
(7.2)
78.4 ( 0.4
75.5 ( 0.4
74.4 ( 0.4
75.0 ( 0.4
70.9 ( 0.4
71.2 ( 0.4
13.3 ( 1.2
12.6 ( 1.1
10.5 ( 0.8
10.9 ( 0.8
9.4 ( 0.7
9.2 ( 0.7
1.02
1.07
1.04
11.6
10.6
9.7
31.1
34.0
37.2
Boc
Moc
Moc
Ac
100
25
(51.1)
61.7
(52.1)
(24.3)
35.6
(23.2)
(17.2)
30.8
(17.4)
Ac
100
a d spacings of the columnar hexagonal phase; b Peak amplitude scaled to the sum of the observed diffraction peaks (a.u.)arbitrary units); c Experimental
d
2
density measured at 22 °C; Number of dendrons per column stratum µ ) ( 3NAD tF)/2M, where NA ) 6.0220455 × 1023 mol-1 is Avogadro’s number,
x
M is the molecular weight of the dendron, and t ) 4.7 Å is the average height of the column stratum. e Projection of the solid angle of R′ ) 360/µ.
structure, whereas Moc and Ac mediate a long-range13e,g
intracolumnar helical structure that extends between 16 and 20
layers of column strata. In the case of the supramolecular
structure designed from the Moc-based dendritic dipeptide, the
calculated radius of the intracolumnar helix is 14 ( 4 Å. The
XRD data together with the experimental densities and µ values
from Table 2 and molecular modeling experiments were used
to construct a molecular model of the supramolecular
columns.9a,10b The cross sections of the supramolecular pores,
without the dendrons, are shown in Figure 4. These structures
demonstrate the ability of the protective groups to program the
size of the supramolecular pore, their intramolecular order, and
the stability of the pore as a function of temperature.
Supramolecular Pore Structure and Stability in Dilute
Solution. Previously, we reported that the circular dichroism
(CD) and UV spectra of self-assembled dendritic dipeptides in
thin films and in dilute solution are similar. Therefore, the
supramolecular structures self-assembled from dilute solution
and in the solid state are similar.9a Self-assembly of dendritic
dipeptides occurs in hydrophobic solvents such as cyclohexane,
methylcyclohexane, and linear alkanes.9a,10 The self-assembly
in dilute solution can be monitored by a combination of
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J. AM. CHEM. SOC. VOL. 127, NO. 50, 2005 17905

A R T I C L E S
Percec et al.
Figure 3. (top) X-ray diffraction patterns collected at different temperatures and (bottom left) wide-angle X-ray diffraction plots for aligned fibers (fiber
axis is horizontal) of (4-3,4-3,5)12G2-CH2-X-L-Tyr-L-Ala-OMe, X ) Boc (in Φh), Moc (in Φhio), Ac (in Φhio); i ) short-range helical feature (∼4.5
io
Å); t ) tilt feature (64 ( 9°); j ) (10), (11), and (20) reflections of the Φh and Φh phases; m ) higher-order (hk0) reflections; k ) registry along the
column feature (see the insets for representative values; the correlation length is between 16 and 22 layers); h ) long-range helical feature. The calculated
helix radius is 14 ( 4 Å.
eochemical information of the peptide is communicated to the
dendron, and subsequently, a certain dendron conformation
mediates the self-assembly of the peptide. However, as dem-
onstrated previously and observed here, any change in the
structure of the dipeptide or its protective groups induces
changes in the molecular conformation of the dendron and in
the supramolecular conformation of the dendrimer.10b The
reverse of this trend is also valid. This regulation process
resembles the allosteric control in proteins.10b,15 The change of
the protective group from Boc to Moc and to Ac induces
substantial changes in the CD spectrum of the supramolecular
Figure 4. Molecular models of the helical porous columns (cross sections)
structure. The Cotton effects observed at various wavelengths
constructed from XRD and density data and molecular modeling showing
in Boc-based dendritic dipeptide change both their sign and
amplitude in Moc- and Ac-based structures. For the purpose of
the present discussion, it is important to notice that the ellipticity
of the maximum Cotton effect of the CD spectra increases at
the transition from Boc to Moc and Ac. This trend is in line
with the short-range versus long-range intramolecular helical
structure observed in bulk experiments (Figure 5). Additional
important information obtained from these experiments refers
to the melting temperature (Tm) of the individual supramolecular
columns that is obtained from the plot of ellipticity versus
temperature (lower insets in Figure 5).
the influence of the protective group on the structure of the hydrophobic
pores of supramolecular self-assemblies based on (4-3,4-3,5)12G2-CH2-
X-L-Tyr-L-Ala-OMe, X ) Boc, Moc, Ac, at 25 °C. Color code: -CH3
from the protective groups X of Tyr, blue; -CH3 of the methyl ester of
Ala, white; C, gray; O, red; N-H, green. For simplicity, the dendrons are
not shown.
spectroscopic methods that include UV spectroscopy, 1H NMR
spectroscopy, and CD.9a Here, we discuss the self-assembly in
solution with the aid of temperature-dependent CD experiments.
The CD spectra obtained as a function of temperature during
the self-assembly of these dendritic dipeptides are shown in
Figure 5. The Cotton effect of the molecular solution of the
dendritic dipeptides at high temperature (the right insets in
Figure 5) appears at 230 nm. Upon cooling, in all cases, Cotton
effects associated with the aromatic part of the dendritic
dipeptide are observed.9a,10 The role of the dipeptide stereo-
chemistry is to select the helix sense of the helical supramo-
lecular structure self-assembled from the dendron.9a The ster-
The transition from Boc to Moc and to Ac also increases Tm
from 22 to 38.5 and 47.5 °C, respectively (Figure 5, lower right
insets). This result correlates with the trend of the transition
temperatures obtained in the solid state (Figure 1, Table 1) and
is extremely important because it demonstrates that the protec-
tive groups of the dipeptide provide a mechanism for enhancing
9
17906 J. AM. CHEM. SOC. VOL. 127, NO. 50, 2005

Helical Pores in Self-Assembled Dendritic Dipeptides
A R T I C L E S
Figure 5. CD spectra of (4-3,4-3,5)12G2-CH2-Boc-L-Tyr-L-Ala-OMe (1.6 × 10-4 M in cyclohexane) and (4-3,4-3,5)12G2-CH2-X-L-Tyr-L-Ala-
OMe, X ) Moc, Ac (1.1 × 10-4 M in methylcyclohexane/cyclohexane 3/1 v/v). Arrows indicate trends upon increasing temperature. The upper insets
illustrate the Cotton effect associated with the molecular solution of the dendritic dipeptide. The bottom insets show the molecular ellipticity as a function
of temperature at the wavelength at which the intensity of the Cotton effect is maximum. The melting temperatures (Tm) determined from these plots are also
indicated.
Figure 6. (top) Conformations of (4-3,4-3,5)12G2-CH2-X-L-Tyr-L-Ala-OMe, X ) Boc, Moc, Ac, in their supramolecular structures from Figure 4
(only the first methyl ether of the dendron is shown). (bottom) Correlation between the protective group of the dipeptide and the pore (Dpore) and column
(Dcol) diameters self-assembled from dendritic dipeptides. The structure of the protective group changes the projection of the solid angle (R′X) of the dendritic
dipeptide and results in different Dpore and Dcol values. Color code: -CH3 from the protective group of Tyr, blue; -CH3 of the methyl ester of Ala, white;
C, gray; O, red; N-H, green. The atoms that generate the in-layer H-bonds of the supramolecular columnar assembly are labeled j-k and l-m (see Figures
7 and 8 for details).
the thermal stability of the single pore required for single-
channel transport experiments carried out in artificial mem-
branes.9
Mechanism of Pore Programming by the Protective
Groups of the Dipeptide. The cooperative transfer of structural
and stereochemical information between the dendron and the
dipeptide is responsible for the mechanism by which the
structure and stability of the pore are programmed. Figure 6
shows the conformation of the dipeptides as they exist in the
dendritic dipeptides forming the pore structures shown in Figure
9
J. AM. CHEM. SOC. VOL. 127, NO. 50, 2005 17907

A R T I C L E S
Percec et al.
Figure 7. H-bonding network (lengths in angstroms) of the supramolecular pore structures from Figure 4 of (4-3,4-3,5)12G2-CH2-X-L-Tyr-L-Ala-
OMe, X ) Boc, Moc, Ac, at 25 °C. Four dipeptides from two layers are illustrated: In the top layer, the two dipeptides are shown with C atoms in light
blue and dark blue; in the bottom layer, one of the two dipeptides has the C atoms in gray, and the other one has them in gold; O, red; N, green; phenyl of
Tyr and H atoms are not shown except the N-bound H, which is shown in white. The column axis is vertical, and the in-layer directional H-bonds are labeled
l-m and j-k.
from Boc- to Moc- and to Ac-based dendritic dipeptides is
accompanied by a decrease in the number of dendrons required
to create a column stratum (µ). The change in µ will affect the
H-bond length and strength in the dipeptide network and,
therefore, will determine the stability of the pore (Figures 7
and 8).
As shown previously,9a the self-assembly of the dendron
induces a parallel arrangement of the dipeptide in the helical
porous structure. This arrangement mediates the construction
of a supramolecular network of H-bonds. This helical and
parallel arrangement of H-bonded peptides is not known in
biological and native artificial proteins and peptides that prefer
an antiparallel arrangement during H-bonding. Figure 7 il-
lustrates the impact of the protective groups in this H-bonded
network. The transition from Boc to Moc and to Ac induces
the shortening of the H-bond distances and consequently
increases the stability of the porous structures both in the solid
state (Figure 1) and in solution (Figure 5). This mechanism
programs the stability of the internal structure of the pore. The
number of dendrons (µ) forming the cross section or the stratum
of the porous column (Table 2) determines the size of the pore
(Figure 4), as shown in the schematic representation in Figure
8. Moc and Ac protective groups mediate the self-assembly of
a higher intracolumnar order, which provides an enhanced
supramolecular polymer effect10a,16 through H-bonding. This
supramolecular polymer effect explains the increase in the
stability of the supramolecular columns both in the solid state
and in solution via the same thermodynamic schemes elaborated
for the covalent polymer effect.16 It is extremely rewarding to
see the remarkable power of the protective groups and their
Figure 8. (left) Top views of one layer of the columns whose cross sections
are shown in Figure 4 and (right) detail of the H-bonding for (4-3,4-3,5)-
ability to provide the simplest architectural motif for the design
and construction of porous structures from dendritic dipeptides.
Previous approaches to control µ, R′, Dpore, and pore stability
were accessible through different chemical structures of the self-
assembling dendron attached to the dipeptide,10a the dipeptide
stereochemistry,9b and the dipeptide structure.9a
12G2-CH2-X-L-Tyr-L-Ala-OMe, X ) Boc, Moc, Ac, at 25 °C. The
first two H-bonds seen when viewing Figure 7 from its top (m-l and j-k)
are shown on the right side. The long-range helical feature calculated from
fiber XRD and indicated by h in Figure 3 is shown in the middle right side
for Moc. Color code: -CH3 from the protective groups X of Tyr, blue;
-CH3 of the methyl ester of Ala, white; C, gray; O, red; N-H, green. The
in-layer directional H-bonds are labeled j-k and l-m (see Figures 6 and 7
for details). For simplicity, only the first methyl ether of the dendron is
shown in each case.
(15) (a) Monod, J.; Changeux, J.-P.; Jacob, F. J. Mol. Biol. 1963, 6, 306-329.
(b) Perutz, M. Mechanism of CooperatiVity and Allosteric Regulation in
Proteins; Cambridge University Press: Cambridge, U.K., 1990. (c) Evans,
P. R. Curr. Opin. Struct. Biol. 1991, 1, 773-779.
(16) (a) Percec, V.; Keller, A. Macromolecules 1990, 23, 4347-4350. (b) Percec,
V.; Ahn, C.-H.; Ungar, G.; Yeardley, D. J. P.; Mo¨ller, M.; Sheiko, S. S.
Nature 1998, 391, 161-164. (c) Percec, V.; et al. J. Am. Chem. Soc. 1998,
120, 8619-8631.
4. The projections of the dendritic dipeptide conformations,
together with the values of the projections of their solid angles
(R′)14 from Table 2, are shown in Figure 6. An increase in R′
9
17908 J. AM. CHEM. SOC. VOL. 127, NO. 50, 2005

Helical Pores in Self-Assembled Dendritic Dipeptides
A R T I C L E S
Conclusions
stability, and conformation of the dendron and of the supramo-
lecular dendrimer in the supramolecular helical pores. This
concept provides the simplest architectural motif that expands
dramatically the scope and limitations of self-assembling
dendritic dipeptides in the construction of supramolecular
structures programmed on all structural levels.17
Self-assembling dendritic dipeptides provide a general strat-
egy for the design of supramolecular helical porous protein
mimics and of their function.9,10 Therefore, elucidation of the
role of each molecular component of the dendritic dipeptide in
the self-assembly process is required. Previously, we reported
preliminary data that provided fundamental design principles
with strategies based on dendron architecture and dipeptide
structure and stereochemistry. In this article, we demonstrated
the capability of the protective groups of the dipeptide to
program the dimensions, structure, internal order, thermal
Acknowledgment. Financial support from the National Sci-
ence Foundation (DMR-0548559) and Office of Naval Research
and discussions with Professor G. Ungar of U. Sheffield, U.K.,
are gratefully acknowledged.
Supporting Information Available: Experimental section,
materials, techniques, and synthesis with structural analysis
results. This material is available free of charge via the Internet
at http://pubs.acs.org.
(17) Rowan, A. E.; Nolte, R. J. M. Angew. Chem., Int. Ed. 1998, 37, 63-68.
(b) Hirschberg, J. H. K. K.; Brunsveld, L.; Ramzi, A.; Vekemans, J. A. J.
M.; Sijbesma, R. P.; Meijer, E. W. Nature 2000, 407, 167-170. (c) Green,
M. M.; Park, J.-W.; Sato, T.; Teramoto, A.; Lifson, S.; Selinger, R. L. B.;
Selinger, J. V. Angew. Chem., Int. Ed. 1999, 38, 3139-3154. (d) Hecht,
S. Mater. Today 2005, 8, 48-55. (e) Emrick, T.; Frechet, J. M. J. Curr.
Opin. Colloid Interface Sci. 1999, 4, 15-23.
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