Self-assembly, structural, and retrostructural analysis of dendritic dipeptide pores undergoing reversible circular to elliptical shape change

Article abstract of DOI:10.1021/ja0611902

The synthesis of dendritic dipeptides (4-3,4-3,5-4) 12G2-CH ₂-Boc-L-Tyr-L-Ala-OMe and (4-3, 4-3,5-4) 12G2-CH₂-Boc-D- Tyr-D-Ala-OMe is described. These dendritic dipeptides self-assemble into porous elliptical and circular columns tha

Full text of DOI:10.1021/ja0611902

Published on Web 04/29/2006
Self-Assembly, Structural, and Retrostructural Analysis of
Dendritic Dipeptide Pores Undergoing Reversible Circular to
Elliptical Shape Change
Mihai Peterca,‡ Virgil Percec,*,† Andre´s E. Dulcey,† Sami Nummelin,†
Stephanie Korey,† Monica Ilies,† 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 February 19, 2006; E-mail: percec@sas.upenn.edu
Abstract: The synthesis of dendritic dipeptides (4-3,4-3,5-4)12G2-CH2-Boc-L-Tyr-L-Ala-OMe and (4-3,
4-3,5-4)12G2-CH2-Boc-D-Tyr-D-Ala-OMe is described. These dendritic dipeptides self-assemble into porous
elliptical and circular columns that in turn self-organize into centered rectangular columnar and hexagonal
columnar periodic arrays. The transition from porous elliptical to porous circular columns is mediated in a
reversible or irreversible way by the thermal history of the sample. A method to determine the dimensions
of hollow elliptical and circular columns by the reconstruction of the small-angle powder X-ray diffractograms
of the centered rectangular or hexagonal columnar lattices was elaborated. This technique together with
wide-angle X-ray experiments performed on aligned fibers provided access to the structural and
retrostructural analysis of elliptical supramolecular pores. This procedure is general and can be adapted
for the determination of the dimensions of pores of any columnar shape.
Introduction
solution and in solid state. This behavior limits their structural
analysis by combinations of solution and solid state comple-
Natural pore-forming proteins and their remodeled structures
exhibit a diversity of biological and biologically inspired
functions such as transmembrane channels,1 viral helical coats,2
reversible encapsulation,3 stochastic sensing,4 and patogenic5
and antibiotic activity.6 Natural porous proteins are stable in
solution and in solid state. Various synthetic strategies to porous
and tubular supramolecular assemblies have been elaborated.7
However, with few exceptions,8 porous protein mimics do not
assemble into periodically ordered structures that are stable in
mentary techniques. Our laboratory reported the self-assembly
of amphiphilic dendritic dipeptides to produce helical pores that
are stable both in solution and in solid state.9 For the same
dendron and dipeptide, the internal structure and stability of
the pore are programmed by the stereochemistry10a and the
protective groups10b of the dipeptide and by the number of the
methylenic units in the alkyl groups attached to the periphery
of the dendron.10c This process is cooperative and involves
allosteric regulation.11 The same principles may apply to the
self-assembly of dendritic dipeptides based on different den-
drons12 and dipeptides.
† Roy & Diana Vagelos Laboratories, Department of Chemistry, Uni-
versity of Pennsylvania.
‡ Department of Physics and Astronomy, University of Pennsylvania.
(1) (a) MacKinnon, R. Angew. Chem., Int. Ed. 2004, 43, 4265-4277. (b) Agre,
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Duan, H.; Magonov, S. N.; Vinogradov, S. A. Nature 2004, 430, 764-
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Verkley, A. J.; Drenth, W. Isr. J. Chem. 1984, 24, 297-301. (b) Jullien,
L.; Lehn, J.-M. Tetrahedron Lett. 1988, 29, 3803-3806. (c) Cross, G. G.;
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J. AM. CHEM. SOC. 2006, 128, 6713-6720
6713

A R T I C L E S
Peterca et al.
Scheme 1. Synthesis of the New Dendritic Dipeptides (4-3,4-3,5-4)12G2-CH2-X, X ) Boc-L-Tyr-L-Ala-OMe and Boc-D-Tyr-D-Ala-OMe.
Porous structures self-assembled from dendritic dipeptides
reported up to now,9,10,12 as well as porous structures assembled
from other architectures,7,8 have a circular shape of the pore.
Nonetheless, natural pore-forming proteins display also other
pore shapes. A representative example is the hourglass shape
of aquaporin.1b Currently we are searching through libraries of
supramolecular porous structures forming lattices that have the
potential to indicate strategies to noncircular pore shapes.
Preliminary reports10c,13 have indicated the possibility of
generating elliptical pores from several dendritic alcohols that
were used as precursors to dendritic dipeptides. However, their
c2mm centered rectangular columnar (Φr-c) lattice exhibited a
small number of X-ray diffraction peaks resulting in low spatial
resolution. In addition, structural and retrostructural analysis
methods for supramolecular pores were available only for
structures with circular shape.9
We now report the synthesis of dendritic dipeptides that self-
assemble into circular pores which, depending on their kinetic
treatment and on the degree of order of the pore, undergo either
reversible or irreversible circular-to-elliptical shape changes. A
combination of electron density maps together with the recon-
struction of their small-angle and wide-angle X-ray diffraction
(XRD) experiments performed on powder and oriented fibers
combined with experimental densities was used to develop
methods for the structural and retrostructural analysis of elliptical
pores.
(60% yield) (Scheme 1). Reduction of 3 with LiAlH4 in THF
yielded (4-3,4-3,5-4)12G2-CH2OH (4) (95% yield). Mitsunobu
etherification of Boc-L-Tyr-L-Ala-OMe (5a)9 and Boc-D-Tyr-
D-Ala-OMe (5b)9 with 4 generated the enantiomeric dendritic
dipeptides (4-3,4-3,5-4)12G2-CH2-Boc-L-Tyr-L-Ala-OMe (6a)
(69%) and (4-3,4-3,5-4)12G2-CH2-Boc-D-Tyr-D-Ala-OMe (6b)
(60%). A combination of 1H and 13C NMR, HPLC, and
MALDI-TOF techniques was used to demonstrate the structure
and purity (>99%) of all intermediary and final compounds.
Structural Analysis of the Supramolecular Assemblies.
The structural analysis of the supramolecular porous assemblies
generated from these dendritic dipeptides was carried out by a
combination of differential scanning calorimetry (DSC) and
small- and wide-angle powder and fiber XRD experiments. The
strategy employed is outlined below.
The porous structure of the columns was identified by the
enhanced intensity of the higher order XRD diffractions and
was visualized by the reconstructed electron density maps
calculated from the XRD data.9a,10 The size of the elliptical pore
was determined by elaborating a method for the reconstruction
of the XRD peak positions and intensities using the electron
density of the dendritic dipeptide and considering a three-phase
intracolumnar model consisting of aliphatic, aromatic, and
dipeptide regions and a hollow center of the column, as
suggested by the electron density map. This strategy is similar
to that elaborated for circular porous columns.9a
Transition temperatures and their enthalpy changes were
obtained by DSC, and the phases associated with these transi-
tions were assigned by XRD. The DSC analysis of the as
prepared (4-3,4-3,5-4)12G2-CH2-Boc-L-Tyr-L-Ala-OMe and (4-
3,4-3,5-4)12G2-CH2-Boc-D-Tyr-D-Ala-OMe show that they are
already assembled into supramolecular columns (Figure 1).
Results and Discussion
Synthesis of (4-3,4-3,5-4)12G2-CH2-Boc-L-Tyr-L-Ala-OMe
and (4-3,4-3,5-4)12G2-CH2-Boc-D-Tyr-D-Ala-OMe. The sec-
ond generation dendron (4-3,4-3,5)12G2-CH2OH (1) synthesized
as reported previously9,14 was etherified with 2 under Mitsunobu
reaction conditions15 to produce (4-3,4-3,5-4)12G2-CO2CH3 (3)
On cooling from the isotropic state both dendritic dipeptides
are self-assembled into columns that self-organize into a
monotropic hexagonal columnar phase (Φh), followed by an
enatiotropic c2mm centered rectangular columnar lattice with
(13) Percec, V.; Peterca, M.; Sienkowska, M. J.; Ilies, M. A.; Aqad, E.; Smidrkal,
J.; Heiney, P. A. J. Am. Chem. Soc. 2006, 128, 3324-3334.
(14) (a) Percec, V.; Cho, W.-D.; Ungar, G.; Yeardley, D. J. P. J. Am. Chem.
Soc. 2001, 123, 1302-1315. (b) 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.
(15) Mitsunobu, O. Synthesis 1981, 1-28.
iï
intracolumnar order (Φr-ciï). On heating, at 83 °C the Φr-c
lattice undergoes a transition to a p6mm hexagonal columnar
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6714 J. AM. CHEM. SOC. VOL. 128, NO. 20, 2006

Dendritic Dipeptide Pores Undergoing Shape Change
A R T I C L E S
Figure 2. Small-angle X-ray diffraction plots recorded at various temper-
atures in the supramolecular columnar structures self-assembled from
(4-3,4-3,5-4)12G2-CH2-Boc-L-Tyr-L-Ala-OMe. Below the isotropisation
iï
temperature, the freezing of the higher order Φh phase is observed (see
Figure 1. Second heating and cooling DSC scans (10 °C/min) of (4-3,4-
3,5-4)12G2-CH2-X; X ) Boc-L-Tyr-L-Ala-OMe, Boc-D-Tyr-D-Ala-OMe.
Transition temperatures (°C) and enthalpies changes (kcal/mol, in paren-
iï
also Figure 3). Φr-c ) centered rectangular columnar phase; Φh ) hex-
iï
agonal columnar phase, Φh ) hexagonal columnar phase with intraco-
lumnar order; q ) (4π/λ) sinθ ) momentum transfer; a.u. ) arbitrary units.
iï
theses) are indicated. Φr-c ) centered rectangular columnar phase with
The sequence of dark (on heating) and light (on cooling) green arrows shows
iï
intracolumnar order; Φh ) hexagonal columnar phase; Φh ) hexagonal
iï
the reversible Φr-ciï-Φhiï-isotropic-Φh-Φr-c transition, while the
columnar phase with intracolumnar order; g ) glass; i ) isotropic liquid.
sequence of dark green up to 95 °C and black arrows shows the irreversible
First heating scans (not shown) are identical with the second heating scans.
iï
Φr-ciï-Φh transition.
phase with intracolumnar order (Φhiï).10b,c The short-range
iï
iï
intracolumnar order of the Φr-c and Φh phases was estab-
lished by using wide-angle XRD experiments carried out on
both powder and aligned fibers. These experiments will be
discussed later. At about 99 °C the Φhiï lattices of both dendritic
dipeptides transform into an isotropic liquid that is generated
from self-assembled columns as demonstrated by XRD (Sup-
porting Information, Figure SF1). The sequences of heating and
cooling illustrated in Figure 1 provide strategies for the
reversible and irreversible interconversion between the circular
iï
columns that assemble in the Φh phase and the elliptical
iï
columns that assemble in the Φr-c phase. The identification
of the Φr-ciï and Φhiï phases was accomplished by small-angle
powder XRD experiments (Figure 2 and Supporting Information,
Figure SF1). When the sample was heated from 20 °C up to
the isotropic phase and back, the sequence of phases from Figure
1 was reproducible (Supporting Information, Figure SF1).
However, when the sample was heated only up to the Φhiï phase
iï
(95 °C) and cooled to 30 °C, the Φr-c phase was not
regenerated (Figure 2). The existence of intermediate range
intracolumnar order (io)10b,c in the supramolecular columns
iï
iï
forming the Φr-c and Φh phases was established by wide-
angle XRD experiments carried out on powder and on aligned
iï
iï
fibers (Figures 3 and 4). The Φr-c and Φh phases exhibit a
5.0 Å stacking of the aromatic rings (Figure 4). The Φhiï phase
exhibits a correlation length of about 60 layers (k), and a 62°
tilt of the dendrons with respect to the column axis. The io of
the hexagonal phase was identified by the presence of short-
range helicity and tilt, and by the longer range registry features.
The helical structure of the columns was also supported by
circular dichroism experiments (Supporting Information Figure
SF9).
Figure 3. Wide-angle X-ray diffraction patterns recorded at the temper-
atures indicated in the figure on aligned fibers of (4-3,4-3,5-4)-12G2-
CH2-X. (a and b) X ) Boc-L-Tyr-L-Ala-OMe; (a) in Φr-ciï, (b) in Φhiï; (c
and d) X ) Boc-D-Tyr-D-Ala-OMe; (c) in Φr-ciï, (d) in Φhiï; i, j ) short-
range features arising from helical intracolumnar order (4.6 Å for i and 5.0
Å for j); e ) strong equatorial feature (4.8 Å); k ) diffraction pattern features
corresponding to 5.0 Å stacking of the aromatic rings along the column
axis (the estimated correlation length is ∼60 layers); m ) dendron tilt (62
( 8°); n ) high order (hk0) reflections.
Mechanism of the Reversibility of the Elliptical to Circular
Shape Change. The reversibility vs irreversibility of the
transition from elliptic to circular columns was investigated by
a combination of DSC and XRD experiments. Figure 1 shows
9
J. AM. CHEM. SOC. VOL. 128, NO. 20, 2006 6715

A R T I C L E S
Peterca et al.
Figure 5. Reconstructed electron density maps for the lattices generated
from (4-3,4-3,5-4)12G2-CH2-Boc-L-Tyr-L-Ala-OMe: (a) hollow Φhiï cal-
culated using experimental diffraction amplitudes; (b) hollow Φr-ciï using
experimental diffraction amplitudes; (c) plot of the relative electron densities
profiles as a function of column radius for the two phases; (d) hollow Φr-c
generated from calculated diffraction amplitudes given by the three-level
model.
Figure 4. Chi plot of the X-ray diffraction fiber pattern shown in Figure
3b (a); (4-3,4-3,5-4)12G2CH2Boc-L-Tyr-L-Ala-OMe powder and fiber
q-plots at the indicated temperatures (b). Legend: i ) short-range features
arising from helical intracolumnar order (4.6 Å); e ) strong equatorial
feature (4.8 Å); m ) dendron tilt; k ) diffraction pattern features
corresponding to 5.0 Å stacking of the aromatic rings along the column
axis (the estimated correlation length is ∼60 layers).
iï
close proximity to glass transition (Tg). Therefore, only the
transition from Φhiï to isotropic liquid is kinetically controlled.
This analysis explains the mechanism of the reversible Φh to
Φr-ciï and Φr-ciï to Φhiï and of the irreversible transition from
Φhiï to Φr-ciï phases. During the second and subsequent heating
and cooling scans from 20 °C to isotropic liquid the order in
the second heating and cooling DSC scans of both dendritic
dipeptides. The first, second, and subsequent heating and cooling
DSC scans are identical. A DSC analysis of this sequence, which
iï
consists of heating to Φhiï, annealing in the Φh phase for at
iï
the Φr-c phase is higher than that in the less ordered Φh and
least 5 min, cooling to 20 °C, and reheating to isotropic liquid
iï
of unannealed Φh phases, and this provides a mechanism for
iï
iï
does not show the Φh to Φr-c transition on cooling and
reheating (Figure 2). The very small supercooling of all
transition temperatures and their associated enthalpy changes
demonstrate reversible and thermodynamically controlled transi-
tions to the Φr-ciï, Φhiï, and Φh phases when the sample was
heated from 20 °C to isotropic and back with 20, 10, and 5
°C/min, with a higher isotropization enthalpy at the lowest
heating rate only. However, when the sample was heated to
the reversibility of the process. However, upon annealing, the
iï
order of the Φhiï phase becomes higher than that of the Φr-c
iï
phase. Subsequently, the formation of the Φr-c phase from
the higher order Φh on cooling becomes thermodynamically
iï
inhibited. This trend is in agreement with thermodynamic
schemes reported previously.16 This thermal analysis clarifies
the sequence discovered by the XRD experiments that is
presented in Figure 2.
iï
the Φh phase, maintained for 5 min in this phase, cooled to
Reconstruction of Electron Density Maps of Columnar
Hexagonal and Columnar Rectangular Lattices. Electron
density maps9,17 were reconstructed from the peak amplitudes
iï
20 °C, and then reheated, only the Φh phase was observed.
An increase of 60% in the enthalpy change associated with the
iï
Φh to isotropic phase transition was observed under these
iï
from small-angle powder XRD of the Φh (Figure 5a) and
conditions. Without annealing, the isotropization enthalpy
iï
iï
Φr-c (Figure 5b) lattices. The Φh phase exhibits seven
change is 5.4 kcal/mol (Figure 1), and after annealing in the
iï
diffraction peaks, and the Φr-c phase shows 10 diffraction
iï
Φh phase, it is 8.7 kcal/mol. This substantial increase in the
peaks. All of them were used in the calculation of the electron
Φhiï to i enthalpy change demonstrates an enhancement in the
density maps. All possible phase choices for the X-ray diffrac-
iï
order of the Φh phase that most probably approaches 3-D
iï
tion amplitudes of the Φr-c phase were investigated. The
hexagonal crystal order. Annealing for more than 5 min in the
solution proposed here was based on the match of the electron
iï
Φh phase results in a further increase in the enthalpy change
iï
associated with the Φhiï - i transition. Annealing in the Φr-c
(16) Percec, V.; Keller, A. Macromolecules 1990, 23, 4347-4350.
(17) Balagurusamy, V. S. K.; Ungar, G.; Percec, V.; Johansson, G. J. Am. Chem.
Soc. 1997, 119, 1539-1555.
phase does not increase the order of the phase. This is due to a
iï
very slow dynamic in the Φr-c phase that is induced by its
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Dendritic Dipeptide Pores Undergoing Shape Change
A R T I C L E S
iï
iï
density distribution of the Φr-c phase with that of the Φh
phase. In both cases the electron-density maps show that the
dendrons self-assemble into hollow columns. These columns
iï
are circular in the case of Φhiï and elliptical in the case of Φr-c
.
As shown in Figure 5b, the elliptical columns are aligned with
iï
the long axis of their cross-section along the b axis of the Φr-c
lattice. The color code shows high electron density surrounding
the low electron density hollow center. The high electron density
(marked in red) is generated by the dipeptide and the aromatic
parts of the dendron which are considered to constitute a single
microphase. The periphery of the column has low electron
density that is generated by the aliphatic part of the dendron,
and is highlighted in green and blue. The sharp separation among
the pore, dipeptide plus aromatic, and aliphatic regions indicates
a three-phase microsegregated structure in the supramolecular
column (Figure 5a,b,c). The minimum of the electron density
in the center of the column is below the electron density from
the aliphatic part that is located at the periphery of the column.
This indicates that a pore penetrates through the center of the
column.
Figure 6. Three-level models of the elliptical asymmetric and of the circular
symmetric columns derived from the electron density maps. (a) Raliph
)
the aliphatic region of the column; Rarom ) the combined peptide and
aromatic region of the column; Rpore ) the hollow region; (b) a, b ) c2mm
lattice vectors; their orientation in the (xy) plane is indicated; (c) the
distortion along a preferred direction of the p6mm phase generates the c2mm
phase; each of the two possible directions is highlighted by black and white
double arrows, respectively; (d) the structure of the dendritic dipeptide (4-
3,4-3,5-4)12G2-CH2-Boc-L-Tyr-L-Ala-OMe that self-assembles into porous
Calculation of the Elliptical Pore Size by the Reconstruc-
tion of the XRD. The calculation of the elliptical pore size was
accomplished by the reconstruction of the XRD via a least-
squares fit of the observed positions and amplitudes of the
diffraction peaks to those calculated based on a simplified model
consisting of cylindrical or elliptical shells of constant density.
The relative electron density in each shell is calculated from
the molecular structure of the dendritic dipeptide, and therefore,
the only fitting parameters are the shell radii. This approach
was used previously to reconstruct the lyotropic hexagonal phase
generated from lipids18 and the circular porous hexagonal phase
reported from our laboratory.9a Figure 7 outlines the three-level
model of the elliptical and of the circular columns derived from
the electron-density maps in Figure 5. The structure of the
dendritic dipeptide uses the same color code as that in the
supramolecular column shown in Figure 5d. The numbers of
electrons in the aromatic and dipeptide (Narom) and in the
aliphatic (Naliph) parts of the dendritic dipeptide molecule are
also shown in Figure 6d. The reconstruction of the powder XRD
that includes both the position and the amplitude of the XRD
of the Φr-c lattice follows the principle of multilevels of constant
electron density used previously.
columns; Narom ) number of electrons in the aromatic region; Naliph
number of electrons in the aliphatic region.
)
major axis radii, respectively (Figure 5b). Substituting eq 2 into
eq 1 and performing the Fourier transform we find
J ( (R q )2 + (R q )2)
x
1
x
x
y y
F(qx,qy) ) F02πRxRy
(3)
(R q )2 + (R q )2
x
x
x
y y
To reduce the number of fitted parameters, we assume that the
ellipticity ratio, defined by ꢀ ) Rx/Ry, is identical for all three
shells of the column. This is equivalent to a smooth and uniform
distortion of the circular columns into elliptical columns. The
complete scattering amplitude then becomes
F(mc2omdeml )(qx,qy) ) Fellipt(Raliph,Faliph) - Fellipt(Rarom,Faliph) +
Fellipt(Rarom,Farom) - Fellipt(Rpore,Farom) (4)
The scattering amplitude F(bq) for a structure with position-
dependent electron density F(br) has the general form:18
where
F(bq) ) F(br)eibqbr dbr,
i ) - 1
(1)
x
∫
J ( (ꢀRq )2 + (Rq )2)
x
1
x
y
F
ellipt(R,F) ) A2πꢀR2F
(5)
(ꢀRq )2 + (Rq )2
For the case of the Φr-c phase, the electron density of the
x
x
y
elliptical cylinder is
Here qx ) 2πh/a and qy ) 2πk/b are the Cartesian components
of the momentum transfer, a and b are the dimension of the
Φr-c lattice, and Faliph, Farom, and Fpore are the charge densities
in the aliphatic, aromatic, and pore regions, respectively (units
e-/Å3), calculated from the number of electrons in each region
(Naliph, Narom, and Npore) and the radii of the different regions
(Raliph, Rarom, and Rpore). A is an overall amplitude prefactor.
When ꢀ ) 1, eq 4 reduces to the equation used previously to
calculate the pores size of circular porous columns9 assembled
in the Φh phase. The experimental XRD intensities are converted
x2
y2
+
e 1
> 1
F0
Rx2 Ry2
x2 y2
F(x,y) )
(2)
+
0
{
Rx2 Ry2
where F0 is constant and Rx, Ry are the semiminor and semi-
(18) Turner, D. C.; Gruner, S. M. Biochemistry 1992, 31, 1340-1355.
9
J. AM. CHEM. SOC. VOL. 128, NO. 20, 2006 6717

A R T I C L E S
Peterca et al.
experimental and calculated scaled amplitudes for these two
lattices are plotted in Figure 7b. Details of the calculation are
presented in the Supporting Information (Figures SF3 and SF5,
Tables ST1 and ST2). The values of the pore diameter (Dpore
)
used to reconstruct the XRD from Figure 7b are summarized
in Table 1. Note that the same three-level least-squares fit
parameters were obtained whether the model was fitted to the
measured intensities or the extracted amplitudes (which depend
on phase), so that the final agreement does not depend on the
choice of phases.
Structural and Retrostructural Analysis of the Supramo-
lecular Pores. The reconstruction of the small-angle powder
XRD allows us to calculate the column (Dcol) and the pore
(Dpore) diameters. However, it does not allow us to determine
the 3-D arrangement of the dendrons in the porous structure.
This information is obtained by combining the results of small-
and wide-angle powder XRD measurements, the analysis of the
aligned fiber samples by wide-angle XRD, the experimental
densities, and molecular modeling.9a In the absence of single-
crystal XRD, fiber XRD experiments generate similar structural
information.19
Wide-angle fiber XRD patterns for the (4-3,4-3,5-4)12G2-
CH2-Boc-L-Tyr-L-Ala-OMe and (4-3,4-3,5-4)12G2-CH2-Boc-
D-Tyr-D-Ala-OMe are shown in Figures 3 and 4. They allow
us to calculate the tilt angle of the dendron, the helical pitch,
and the interaromatic stacking of the aromatic rings along the
column axis. Molecular simulation structures that incorporate
information both from the small-angle powder and wide-angle
fiber XRD results are shown in Figure 8.
Figure 7. X-ray diffraction patterns and plots of (4-3,4-3,5-4)12G2-
CH2-Boc-L-Tyr-L-Ala-OMe (a) in the Φr-ciï (top) and Φhiï (bottom) phases.
iï
(b) Experimental and calculated diffraction amplitudes for the Φr-c and
Φhiï phases of the supramolecular columnar assemblies generated from (4-
3,4-3,5-4)12G2-CH2-Boc-L-Tyr-L-Ala-OMe; a.u. ) arbitrary units.
Structural Analysis of Other Examples of Elliptical Pores.
We reported in several previous publications10c,13 the discovery
of dendrons that self-assemble into elliptical columns that self-
into scaled amplitudes after applying the appropiate multiplicity
and Lorentz corrections:
iï
organize in Φr-c phases exhibiting the signature of a porous
elliptical column in their XRD. However, methods to calculate
their pore dimensions Dpore were not available at that time.
Therefore, we report here the structural analysis of some of these
structures by using the method elaborated in the previous
sections.
I /q m
x
hk hk hk
A(hk)
)
(6)
I
h′k′/qh′k′mh′k′
x
∑
(h′k′)
The precursors to dendritic dipeptides (4-3,4-3,5)12G2-
CH2OH with n ) 6 and 8 show Φhiï and Φr-ciï phases, during
their first heating scans, while, during their cooling and second
where Ihk is the integrated intensity of the X-ray powder peak
with indices h and k, mhk is the multiplicity of the peak, and
the sum in the denominator is performed over all observed
reflections. The experimental amplitudes were least-squares fit
to the amplitudes given by eq 4 by varying the five parameters
of the model: A, Raliph, Rarom, Rpore, and ꢀ. The phase of the
amplitudes, (+- - -) for the Φh and (++- - - - - - - -) for the
Φr-c phases from Figure 7b, were selected as described at the
beginning of the previous subchapter.
heating scans, they exhibit Φr-c and Φr-c phases.10c The
iï
iï
reconstruction of the XRD data for the Φh and Φr-c phases
of (4-3,4-3,5)6G2-CH2OH is detailed in the Supporting Infor-
mation (Table ST4, Figure SF7 and SF8). The electron-density
maps of these two structures are shown in Figure 9b,e. The
column diameters Dcol and Dpore along the a and b axis of the
iï
Φ
r-c lattice are also shown in Figure 9. For comparison, Figure
Figure 7a shows XRD powder intensities of (4-3,4-3,5-4)-
9a,d show the same data for the Φhiï and Φr-c assembled from
(4-3,4-3,5-4)12G2-CH2-Boc-L-Tyr-L-Ala-OMe. As seen in Fig-
ure 9d,e, both the elliptical pores assembled from (4-3,4-3,5-
4)12G2-CH2-Boc-L-Tyr-L-Ala-OMe and from (4-3,4-3,5)6G2-
CH2OH are deformed longitudinally along the b axis of the
Φr-ciï lattice. Also, in both cases ꢀ has almost the same value,
i.e., 0.87 and 0.88, respectively.
12G2-CH2-Boc-L-Tyr-L-Ala-OMe in the Φr-ciï phase at 80 °C
iï
and in the Φh phase at 90 °C. A total of 7 diffraction peaks
iï
iï
were observed in the Φh phase and 10 in the Φr-c phase.
However, for the pore size calculation only the first 4 peaks of
iï
iï
the Φh phase and all 10 of the Φr-c phase were used in the
calculation. The higher order diffraction peaks of the Φhiï have
a larger error in their peak area and, therefore, would introduce
The reconstruction of the XRD of the Φhiï and Φr-ciï phases
iï
a large error in the pore size calculation. For the case of Φr-c
the diffraction peaks higher than 20 and, for the case of Φh
,
,
of (4Pr-3,4Pr-3,5Pr)12G2-CH2OH13 are reported in the Sup-
iï
higher than 10 exhibit enhanced amplitudes (Figure 7a). These
enhanced amplitudes provide a rapid method to screen libraries
of supramolecular columns and detect porous columns. The
(19) (a) Watson, J. D.; Crick, F. H. C. Nature 1953, 171, 737-738. (b) Wilkins,
M. H. F.; Stokes, A. R.; Wilson, H. R. Nature 1953, 171, 738-740. (c)
Franklin, R. E.; Gosling, R. G. Nature 1953, 171, 740-741.
9
6718 J. AM. CHEM. SOC. VOL. 128, NO. 20, 2006

Dendritic Dipeptide Pores Undergoing Shape Change
A R T I C L E S
Table 1. Structural and Retrostructural Analysis of Supramolecular Dendrimers Self-Assembled from (4-3,4-3,5-4)12G2-CH2-X
d10a (Å)
d11c (Å)
d22d (Å)
(Ab, a.u.)
d11a (Å)
d20c (Å)
d13d (Å)
(Ab, a.u.)
d20a (Å)
d02c (Å)
d42d (Å)
(Ab, a.u.)
d21a (Å)
d31c (Å)
d33 d (Å)
(Ab, a.u.)
lattice and
column
g
compound
T
parameters
(Å)
Dpore
(Å)
F20
X
)
(
°C)
phase
(g/cm3)
µh
iï
Boc -L-Tyr-L-AlaOMe
90
65
Φh
71.4a
(47.51)
69.9c
41.1a
(25.26)
68.8c
35.6a
(18.49)
46.5c
26.9a
(8.74)
41.3c
a ) Dcol ) 82.3 ( 0.4
12.0 ( 1.5
1.03
11.5
iï
Φr-c
a ) 138.2 ( 0.4
12
(22.49)
(21.81)
(7.74)
(14.38)
b ) 93.7 ( 0.4
39.0d
31.1d
27.7d
26.1d
Dcol ) 81.6 ( 0.4e
Dcol ) 93.8 ( 0.4f
a ) Dcol ) 82.6 ( 0.4
13.9 ( 1.6e
16.0 ( 1.9f
11.6 ( 1.5
(17.69)
71.7a
(7.41)
41.2a
(4.95)
35.7a
(3.52)
27.0a
iï
Boc -D-Tyr-D-AlaOMe
90
60
Φh
1.03
11.5
12
(49.32)
(24.43)
(17.71)
(8.54)
iï
Φr-c
78.1c
66.5c
48.4c
40.4c
a ) 133.5 ( 0.4
b ) 96.5 ( 0.4
(21.06)
39.2d
(20.08)
(20.71)
31.3d
(6.15)
(5.40)
27.3d
(4.85)
(14.59)
25.69d
(4.56)
Dcol ) 78.9 ( 0.4e
Dcol ) 96.7 ( 0.4f
13.8 ( 1.6e
16.9 ( 2.0f
iï
iï
a d-Spacings of the Φh phase. b Peak amplitude scaled to the sum of the observed diffraction peaks (a.u., arbitrary units). c,d d-Spacings of the Φr-c
iï
iï
phase. e Calculated Dcol or Dpore along the a axis of the Φr-c phase. f Calculated Dcol or Dpore along the b axis of the Φr-c phase. g Experimental density
measured at 20 °C. Number of dendrons per column stratum, µ ) ( 3NAD tF)/2M, where NA ) 6.0220455 × 1023 mol-1 is Avogadro’s number, M is the
molecular weight of the dendron, and t ) 5 Å is the average height of the column stratum; Φhiï ) columnar hexagonal phase with intracolumnar order; Φr-c
) centered rectangular columnar phase; Dcol ) column diameter; Dpore ) pore diameter.
2
h
x
Figure 8. Supramolecular columnar assemblies generated from (4-3,4-3,5-4)12G2-CH2-Boc-L-Tyr-L-AlaOMe. (a) Top view of one layer of the circular
column, together with top and side views of the porous column in the Φhiï phase (bottom); (b) top view of one layer of the elliptical column, together with
iï
top and side views of the porous column in the Φr-c phase (bottom); (c, d) cross-sections of the porous columns from (b) along the two axis (a and b,
iï
respectively) of the Φr-c phase; (e) H-bonding network (in Å) between the dipeptides forming the rigid part of the pore via the mechanism described
previously.9a,10,12 Color code: -CH3 from Boc protective group of Tyr, blue; -CH3 of the methyl ester of Ala, white; C, gray; O, red; N-H, green. For
simplicity, in (a) and (b) only the aromatic part of the dendritic dipeptides (including a methoxy group) is shown, while in (c, d, and e) only the dipeptide
is shown; in (e) four dipeptides from two adjacent and interdigitated layers are illustrated with their C atoms colored differently: in the top layer the C atoms
are in light blue and dark blue, respectively, while in the bottom layer one of the two dipeptides has the C atoms in gray and the other one has them in gold.
iï
porting Information (Table ST3, Figure SF6). Their electron-
density maps are shown in Figure 9c (for the Φh phase) and
9f (for the Φr-c phase). The Dcol and Dpore data for both the
iï
symmetric and asymmetric pores are shown in Figure 9c,d.
9
J. AM. CHEM. SOC. VOL. 128, NO. 20, 2006 6719

A R T I C L E S
Peterca et al.
have an elliptical pore shape, while those forming the Φhiï phase
have a circular pore shape. Although elliptical columns forming
thermotropic Φr-c liquid crystal phases are known,10c,13,14b,20
the elliptical porous columns with intracolumnar order reported
here differ from them and represent the first examples of
noncircular synthetic porous structures that self-organize in
periodic arrays. Previous porous structures exhibited only a
circular pore shape.9,10,12
A strategy to provide a reversible or irreversible change from
elliptical to circular pore shape via different thermal treatment
was elaborated, and its mechanism was elucidated. The dimen-
sions of the elliptical pore were calculated by developing a
method for the reconstruction of the powder XRD patterns of
iï
the Φr-c lattice. Additional X-ray experiments performed on
aligned fibers together with experimental densities, molecular
modeling, and the dimensions of the pore were used to perform
the complete structural and retrostructural analysis of the
elliptical pore. The pore is assembled by a network of dipeptide
H-bonds that provides a rigid and ordered intracolumnar
structure.9,10,12 This intracolumnar order resembles that encoun-
tered in related biological assemblies21 and in circular pores.10b,c
The experiments reported here may facilitate the design of
noncircular porous protein mimics and of membranes that are
externally regulated and mediate separation processes based on
the shape.
Figure 9. Reconstructed 2-D electron-density maps of porous structures
iï
assembled from (4-3,4-3,5-4)12G2-CH2-Boc-L-Tyr-L-Ala-OMe in the Φh
(a) and Φr-ciï (d) phases; from (4-3,4-3,5)6G2-CH2OH in the Φhiï (b) and
Acknowledgment. Financial support by the National Science
Foundation (DMR-0102459 and DMR-0548559), the Office of
Naval Research, and the P. Roy Vagelos Chair at Penn is
gratefully acknowledged.
Φr-ciï (e) phases; and from (4Pr-3,4Pr-3,5Pr)12G2-CH2OH in the Φhiï (c)
iï
and Φr-c (f) phases.
There is a striking difference between the elliptical pore reported
in Figure 9d,e and that from Figure 9f. While in the first two
cases the long axis of the pore is along the b axis of the Φr-c
lattice, in the third case it is along the a axis of the lattice. Even
more striking is the much larger deformation of the asymmetric
pore generated from (4Pr-3,4Pr-3,5Pr)12G2-CH2OH that has ꢀ
) 1.7.
Supporting Information Available: Experimental Section
containing detailed synthesis, structural, and retrostructural
analysis. This material is available free of charge via the Internet
at http://pubs.acs.org.
JA0611902
Conclusions
(20) (a) Percec, V.; Glodde, M.; Bera, T. K.; Miura, Y.; Shiyanovskaya, I.;
Singer, K. D.; Balagurusamy, V. S. K.; Heiney, P. A.; Schnell, I.; Rapp,
A.; Spiess, H.-W.; Hudson, S. D.; Duan, H. Nature 2002, 417, 384-387;
for representative reviews containing also examples of columnar rectangular
liquid crystals assembled from elliptical columns, see: (b) Bushby. R. J.;
Lozman, O. R. Curr. Opin. Colloid Interface Sci. 2002, 7, 343-354. (c)
Tschierske, C. J. Mater. Chem. 2001, 11, 2647-2671. (d) Binnermans, K.
Chem. ReV. 2005, 105, 4148-4204.
The synthesis of the dendritic dipeptides (4-3,4-3,5-4)12G2-
CH2-Boc-L-Tyr-L-Ala-OMe and (4-3,4-3,5-4)12G2-CH2-Boc-
D-Tyr-D-Ala-OMe was reported. Both dendritic dipeptides self-
assemble into porous columns which in turn self-organize into
Φr-ciï and Φhiï lattices. The columns forming the Φr-ciï phase
(21) Bernal, J. D.; Fankuchen, I. Nature 1937, 139, 923-924.
9
6720 J. AM. CHEM. SOC. VOL. 128, NO. 20, 2006