Helical porous protein mimics self-assembled from amphiphilic dendritic dipeptides

Article abstract of DOI:10.1071/CH05092

This manuscript reports the synthesis and the self-assembly of (4-3,4,5-3,5)nG₂-CH₂-Boc-L-Tyr-L-Ala-OMe dendritic dipeptides (n = 12, 16). These dendritic dipeptides self-assemble both in solution and in solid states into helical por

Full text of DOI:10.1071/CH05092

Full Paper
CSIRO PUBLISHING
Aust. J. Chem. 2005, 58, 472–482
www.publish.csiro.au/journals/ajc
Helical Porous Protein Mimics Self-Assembled from Amphiphilic
Dendritic Dipeptides∗
Virgil Percec,A,C Andrés Dulcey,A Mihai Peterca,B Monica Ilies,A Yoshiko Miura,A
Ulrica Edlund,A and Paul A. HeineyB
A Roy & Diana Vagelos Laboratories, Department of Chemistry, Laboratory for Research on the Structure
of Matter, University of Pennsylvania, Philadelphia, PA 19104-6323, USA.
B Department of Physics and Astronomy, Laboratory for Research on the Structure of Matter,
University of Pennsylvania, Philadelphia, PA 19104-6396, USA.
C Corresponding author. Email: percec@sas.upenn.edu
This manuscript reports the synthesis and the self-assembly of (4-3,4,5-3,5)nG2-CH2-Boc-l-Tyr-l-Ala-OMe den-
dritic dipeptides (n = 12, 16).These dendritic dipeptides self-assemble both in solution and in solid states into helical
porous supramolecular columns that mimic porous transmembrane proteins. These supramolecular assemblies
provide also a new class of tubular supramolecular polymers.
Manuscript received: 21 April 2005.
Final version: 1 May 2005.
Introduction
In this paper we report the synthesis (Schemes 2–
4), the structural analysis, and the self-assembly of the
amphiphilic dendritic dipeptides (4-3,4,5-3,5)nG2-CH2-
Boc-l-Tyr-l-Ala-OMe (n = 12, 16) and discuss the similari-
ties and differences between their supramolecular structures
and the structures generated from (4-3,4-3,5)12G2-CH2-
Boc-l-Tyr-l-Ala-OMe dendritic dipeptide (Scheme 1).
A recent communication from our laboratory reported a
new class of amphiphilic dendritic dipeptides that self-
assemble both in solution and in bulk into supramolecular
helical porous or tubular structures.[1] This class of self-
assembling building blocks provides a general synthetic
strategy to mimic the structure of porous transmembrane pro-
teins. Porous transmembrane proteins and their remodelled
structures perform a multitude of biological functions such
as viral helical coats,[2] transmembrane channels,[3,4] medi-
ated protein folding,[5] reversible encapsulation,[6] stochastic
sensing,[7] and pathogenic[8] or antibacterial[9] activity. In
that previous communication[1] we reported the synthesis,
the mechanism of self-assembly, and the structural analy-
sis of the supramolecular porous structures generated from
the dendritic dipeptides (4-3,4-3,5)12G2-CH2-Boc-l-Tyr-l-
Ala-OMe and (4-3,4-3,5)12G2-CH2-Boc-d-Tyr-d-Ala-OMe
(Scheme 1). We also presented preliminary data showing
that a diversity of other dendritic dipeptides constructed
from the same amphiphilic (4-3,4-3,5)12G2-CH2- dendron
attached to other dipeptides, as well as other amphiphilic
dendrons attached to the same Boc-l-Tyr-l-Ala-OMe dipep-
tide, self-assemble into porous supramolecular structures.
These porous protein mimics also represent a new class
of supramolecular tubular polymers with three-dimensional
structure controlled in a cooperative way by the stereochem-
istry of the dipeptide and by the primary structure of the
amphiphilic dendron.[1]
Results and Discussion
The synthesis of (4-3,4,5-3,5)nG2-CH2-Boc-l-Tyr-l-Ala-
OMe follows the sequence of reactions summarized in
Schemes 2–4. The precursors (4-3,4,5)12G2-CH2Cl and
(4-3,4,5)16G2-CH2Cl were synthesized as illustrated in
Scheme 2.[10] The structure of both dendritic dipeptides
1
was confirmed by a combination of 500-MHz H and 125-
MHz 13C NMR spectroscopy and their purity was shown
to be higher than 99% by a combination of thin layer
chromatography (TLC), high pressure liquid chromatogra-
phy (HPLC), and matrix-assisted laser desorption–ionization
time-of-flight (MALDI-TOF) mass spectrometry.
During the self-assembly process the dendron mimics,
through its monodisperse primary structure, the most funda-
mental structural principles of a protein. The conformational
freedom of the benzyl ether units resembles the conforma-
tional freedom of the peptide bond. The 4-3,4,5-3,5 distribu-
tion of repeat units sequences and the amphiphilic character
introduced by the alkyl tails of the dendron resemble the
precise primary structure and the hydrophobic sequences of
∗ Part of this research was discussed in a plenary lecture presented by V.P. at the 27th Australasian Polymer Symposium, 28 November–2 December 2004,
Adelaide.
© CSIRO 2005
10.1071/CH05092
0004-9425/05/060472

Helical Porous Protein Mimics
473
O
H
N
O
O
H
N
H
N
O
OCH3
O
OCH3
O
OCH3
N
H
N
H
N
H
O
O
O
O
O
O
OR
OR
ORꢁ
L-L
D-D
L-L
(CH2)nH
O
O
(CH2)nH
(CH2)12
H
O
O
O
O
O
(CH2)12H
(CH2)nH
O
O
O
O
O
O
(CH2)12
H
O
Rꢁ ꢀO
(CH2)nH
O
O
O
O
(CH2)12
H
O
O
RꢀO
O
O
(CH2)nH
O
O
(CH2)nH
n ꢀ 12, 16
Scheme 1. l-l and d-d stereoisomers of (4-3,4-3,5)12G2-CH2-Boc-Tyr-Ala-OMe and (4-3,4,5-3,5)nG2-CH2-Boc-l-Tyr-l-Ala-OMe
(n = 12, 16).
OH
OH
CH3(CH2)11Br
O
O
(a–c)
OR
ꢂ
OH
ꢂ
OR
Cl
85%
3 Steps
H3CO
H3CO
OH
OR
CH3(CH2)15Br
1
2 R ꢀ C12H25
3 R ꢀ C16H33
4
OR
O
O
O
O
O
(a)
90%
(b,d)
OR
Cl
O
80%
2 Steps
OR
H3CO
O
OR
OR
5 R ꢀ C12H25
6 R ꢀ C16H33
7 R ꢀ C12H25
8 R ꢀ C16H33
Scheme 2. Synthesis of (4-3,4,5-3,5)nG1-CH2Cl (n = 12, 16). Reagents and conditions: (a) K2CO3, DMF, 70◦C; (b) LAH,
THF; (c) SOCl2, CH2Cl2, cat. DMF; (d) SOCl2, DTBMP, CH2Cl2.
proteins. The Boc-l-Tyr-l-Ala-OMe dipeptide fragment of
the dendritic dipeptide plays the role of a tag that detects
structural informations of the dendron in dilute solution and
in the solid state. For example, the ability of the dipeptide to
form hydrogen bonds in solution indicates an all-trans ben-
zyl ether conformation that generates the tapered shape of the
dendron.This tapered shape facilitates the self-assembly pro-
cess. The inability of the dipeptide to form hydrogen bonds

474
V. Percec et al.
O
O
O
H
N
OH
OH
O
OCH3
O
N
H
(a–c)
ꢂ
ꢂ
O
O
Br
Cl
85%
3 Steps
H3CO
OH
9
10
11
O
O
O
O
O
HN
HN
(d)
O
O
(e)
70%
OH
OH
O
O
70%
NH
NH
O
O
O
H3CO
H3CO
12
13
Scheme 3. Synthesis of the dendritic dipeptide precursor [3,5]OHG1-CH2-Boc-l-Tyr-l-Ala-OMe. Reagents and conditions: (a) K2CO3, acetone,
reflux; (b) LAH, THF; (c) SOCl2, CH2Cl2, cat. DMF; (d) K2CO3, DMF, 70◦C; (e) Pd(OAc)2, PPh3, Et3NHCO2H, EtOH, reflux.
OR
OR
O
OR
O
O
HN
O
O
O
O
O
OH
OH
O
O
O
O
K2CO3, DMF, 70ꢃC
HN
NH
O
ꢂ
OR
Cl
60%
OR
O
O
O
O
NH
H3CO
O
13
OR
OR
OR
7 R ꢀ C12H25
8 R ꢀ C16H33
H3CO
O
O
O
OR
14 R ꢀ C12H25
15 R ꢀ C16H33
Scheme 4. Synthesis of (4-3,4,5-3,5)nG2-CH2-Boc-l-Tyr-l-Ala-OMe and (4-3,4,5-3,5)nG2-CH2-Boc-d-Tyr-d-Ala-OMe (n = 12, 16).
in a good solvent for hydrogen bonding, such as chloroform
or methylene chloride, arises from the dynamic equilibrium
between the trans and gauche conformers of the dendron.
This dynamic equilibrium induces a globular conformation
of the dendron (Scheme 5).
hydrophobic effect provided by water during the folding
of proteins. The second role of the dipeptide tag is to
detect the helical structure of the supramolecular assembly in
solution.
By using a combination of 500-MHz 1H NMR spec-
troscopy, UV spectroscopy, and circular dichroism (CD) we
found that (4-3,4,5-3,5)12G2-CH2-Boc-l-Tyr-l-Ala-OMe
adopts an all-trans conformation in the solvophobic sol-
vents cyclohexane and hexane. Figs 1 and 2 show the
UV and CD spectra of (4-3,4,5-3,5)12G2-CH2-Boc-l-Tyr-
l-Ala-OMe and of (4-3,4,5-3,5)16G2-CH2-Boc-l-Tyr-l-
Ala-OMe, respectively, in cyclohexane as a function of
temperature.
For steric reasons the globular dendron conformation
contains the dipeptide at the focal point and, therefore,
prohibits self-assembly in solution. By using this strat-
1
egy, H NMR spectroscopy was used to select solvophobic
solvents for the dendritic dipeptide.[1] Solvophobic sol-
vents change the dynamic equilibrium between trans and
gauche conformers of the benzyl ether into an all-trans
conformation (Scheme 5). This process is similar to the

Helical Porous Protein Mimics
475
H(CH2)n
O
O
H
O
OCH3
H(CH2)n
O
N
N
H
O
(CH2)nH
O
O
O
O
O
H(CH2)n
O
O
O
OCH3
O
H
N
O
O
O
N
H
O
O
O
O
O
O
(CH2)nH
O
O
H(CH2)n
O
O
O
O
H(CH2)n
O
O
O
O
O
O
H(CH2)n
O
H(CH2)n
H(CH2)n
O
O
H(CH2)n
H(CH2)n
n ꢀ 12, 16
Scheme 5. Trans-tapered low-temperature (left) and globular high-temperature (right) conformers of (4-3,4,5-3,5)nG2-CH2-
Boc-l-Tyr-l- Ala-OMe (n = 12, 16).
In both cases increasing the temperature from below 10 to
32◦C generates an increase of UV absorption at 230 nm. This
indicates a change in dendron conformation from globular to
tapered. From 34 to 60◦C this absorption decreases sharply
and subsequently remains constant (Figs 1a and 2a). This
intensity of the Cotton effect observed for (4-3,4,5-3,5)nG2-
CH2-Boc-l-Tyr-l-Ala-OMe (n = 12, 16) in Figs 1b and 2b,
respectively, as compared to the (4-3,4-3,5)12G2-CH2-Boc-
l-Tyr-l-Ala-OMe.[1]
Both dendritic dipeptides exhibit a complex set of colum-
nar hexagonal lattices that are strongly dependent on tem-
perature. The small-angle XRD powder diffractograms are
presented in Fig. 4 while small- and wide-angle patterns
obtained from an oriented fibre are shown in Fig. 5.
The enhanced integrated intensity of the (11), (20), and
(21) reflections from Fig. 4 indicate a porous column. How-
ever, the intensities of these reflections are not as strong
as those of the supramolecular structures generated from
(4-3,4-3,5)12G2-CH2-Boc-Tyr-Ala-OMe with l-l, d-d, l-d,
d-l, and dl-dl stereochemistries. This indicates a smaller
pore diameter for the (4-3,4,5-3,5)16G2-CH2-Boc-l-Tyr-
l-Ala-OMe- and (4-3,4,5-3,5)12G2-CH2-Boc-l-Tyr-l-Ala-
OMe-derived columns than for the (4-3,4-3,5)12G2-CH2-
Boc-Tyr-Ala-OMe columns with l-l, d-d, l-d, d-l, and
dl-dl stereochemistries. The column and pore diameters
(Dcol, Dpore) computed by methods elaborated previously[1]
are reported in Table 1.
The XRD data from Fig. 5 support the helical structure
detected by CD experiments (Figs 1 and 2) and provide
additional details such as dendron tilt angle and registry
along the column axis. The three-dimensional structure of
the porous assemblies of (4-3,4,5-3,5)16G2-CH2-Boc-l-Tyr-
l-Ala-OMe calculated from these XRD experiments is shown
in Fig. 6.
The pore structure is hydrophobic (Fig. 6b). It contains
only the methyl groups of Ala (white) and a methyl group
from Boc (blue). The hydrophobic part of the dipeptide is
incorporated between the hydrophobic part of the pore and
1
shows an intermolecular self-assembly process. H NMR
analysis of this process demonstrates that, during the self-
assembly process, hydrogen bonding takes place.[1] In the
CD spectra of both compounds (Figs 1b and 2b) from 34 to
60◦C, only the Cotton effect associated with the ellipticity of
the dendritic dipeptide at 230 nm is observed. Below 34◦C
the CD spectra correspond to the aromatic part of the den-
dron, and indicate a helical structure in the supramolecular
dendron whose helix sense is selected by the stereochemistry
of the dipeptide.
The detailed structural analysis of the supramolecular
structure resulted from (4-3,4,5-3,5)nG2-CH2-Boc-l-Tyr-l-
Ala-OMe (n = 12, 16) was carried out by small-angle X-ray
diffraction (XRD) on powder and by a combination of
small and wide-angle XRD on oriented fibres, after phase-
transition temperatures were determined by differential scan-
ning calorimetry (DSC) experiments. The DSC analysis
(Fig. 3) shows that in bulk state both dendritic dipeptides self-
assemble into supramolecular columns that self-organize in
two-dimensional column hexagonal (ꢀh) lattices. These lat-
tices facilitate the analysis of the supramolecular columns by
XRD experiments. Both dendritic dipeptides present, after
their glass transition, a three-dimensional columnar hexag-
onal lattice with long-range order. This three-dimensional
order is not observed in the case of the lattice gener-
ated from the (4-3,4-3,5)12G2-CH2-Boc-l-Tyr-l-Ala-OMe
dendritic dipeptides. The higher order of this three-
dimensional lattice is in agreement with the increase in the

476
V. Percec et al.
(a)
(b)
230 nm
34–60ꢃC
100
50
350
300
34–60ꢃC
1.0
0.8
0.6
0.4
0.2
0.0
0.8
0.4
0.0
0
250
ꢄ50
ꢄ100
200
150
270
100
310
230
l (nm)
50
230 270 310
l (nm)
0
8–32ꢃC
ꢄ50
ꢄ100
ꢄ150
ꢄ200
ꢄ250
ꢄ300
ꢄ350
8–32ꢃC
210 230 250 270 290 310
Wavelength (nm)
210 230 250 270 290 310
Wavelength (nm)
Fig. 1. Spectroscopic analysis of the self-assembly of the dendritic dipeptide (4-3,4,5-3,5)12G2-CH2-Boc-
l-Tyr-l-Ala-OMe in cyclohexane (0.5 × 10−4 M). (a) UV spectra; (b) CD spectra. Arrows indicate trends
upon increasing temperature from 8 to 32◦C. Insets: (a) UV absorption and (b) the Cotton effect, respectively,
associated with the molecular solution of the dendritic dipeptide.
(a)
(b)
230 nm
34–60ꢃC
350
300
250
200
150
100
50
50
0
0.6
0.4
0.2
0.0
0.4
0.0
ꢄ50
270
310
230
l (nm)
270
310
230
l (nm)
0
8–32ꢃC
ꢄ50
ꢄ100
ꢄ150
ꢄ200
8–32ꢃC
210 230 250 270 290 310
Wavelength (nm)
210 230 250 270 290 310
Wavelength (nm)
Fig. 2. Spectroscopic analysis of the self-assembly of the dendritic dipeptide (4-3,4,5-3,5)16G2-CH2-Boc-
l-Tyr-l-Ala-OMe in cyclohexane (0.5 × 10−4 M). (a) UV spectra; (b) CD spectra. Arrows indicate trends
upon increasing temperature from 8 to 32◦C. Insets: (a) UV absorption and (b) the Cotton effect, respectively,
associated with the molecular solution of the dendritic dipeptide.

Helical Porous Protein Mimics
477
(o)
(g)
Table 1. XRD structural analysis of the supramolecular porous
columns
ꢇh
ꢇh
(a)
ꢇh
ꢇh
iso
iso
(4-3,4,5-3,5)nG2-CH2-
Boc-l-Tyr-l-Ala-OMe
n = 12
n = 16
(o)
ꢇh
(g)
ꢇh
(b)
T [◦C]
Phase
95
p6mm
54.4 (54.12)
30.7 (16.04)
27.9 (29.84)
98
p6mm
(o)
(g)
ꢇh
ꢇh
iso
iso
(c)
ꢇh
d10 [Å]A (I10 [a.u.])B
d11 [Å]A (I11 [a.u.])B
d20 [Å]A (I20 [a.u.])B
d21 [Å]A (I21 [a.u.])B
a = Dcol [Å]
57.9 (57.73)
32.7 (14.95)
29.2 (15.57)
21.0 (11.74)
66.6 0.4
8.7 1.3
(o)
ꢇh
(g)
ꢇh
ꢇh
iso
(d)
(o)
ꢇh
62.9 0.4
9.2 1.5
(g)
ꢇh
ꢇh
(e)
Dpore [Å]
A d-spacings of columnar hexagonal phase.
B Peak integrated intensity scaled to the sum of the observed diffraction
peaks.
ꢄ20
0
20
40
60
80 100 120
T (ꢃC)
Fig. 3. DSC traces for the assemblies generated from (4-3,4,5-3,5)
nG2-CH2-Boc-l-Tyr-l-Ala-OMe with n = 12 for (a) first heating and
(b) second heating, and with n = 16 for (c) first heating and (d)
second heating and (e) third heating after a 30-min annealing at
compared (Fig. 8). The (4-3,4,5-3,5)nG2-CH2-Boc-l-Tyr-
l-Ala-OMe (n = 12, 16) supramolecular columns show a
decrease of the column diameter of more than 10 Å as com-
pared to (4-3,4-3,5)12G2-CH2-Boc-l-Tyr-l-Ala-OMe (data
compared at the same temperature), whereas the observed
dendron tilt and stacking distance along the column is almost
unchanged. Consequently, the number of dendritic dipeptide
units forming a layer is six for (4-3,4,5-3,5)nG2-CH2-Boc-l-
Tyr-l-Ala-OMe (n = 12, 16) and twelve for (4-3,4-3,5)12G2-
CH2-Boc-l-Tyr-l-Ala-OMe. This difference dictates a
different structure of the hydrogen-bonding network
(Fig. 9).
In contrast to the (4-3,4-3,5)12G2-CH2-Boc-l-Tyr-l-Ala-
OMe structure, the in-layer hydrogen bonds do not form
due to the increased separation between the in-layer adja-
cent dipeptides. The increase in separation is caused by the
smaller number of dendritic dipeptides units per layer. The
structure of the hydrogen bond network of (4-3,4,5-3,5)nG2-
CH2-Boc-l-Tyr-l-Ala-OMe (n = 12, 16) is formed between
the ith and (i 7)th units (that is, cross-layer only).The hier-
archical mechanism of pore assembly can be envisioned by
the sequence of pore structures presented in Fig. 9.
78◦C. Legend: ꢀh: two-dimensional columnar hexagonal lattice; ꢀ(ho)
:
three-dimensional columnar hexagonal lattice; ꢀ(hg): glassy columnar
hexagonal lattice.
n ꢀ 12
n ꢀ 16
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
(10)
(10)
(11) (20)
(11) (20)
(21)
0.00 0.05 0.10 0.15 0.20 0.25 0.30 0.35
q (Åꢄ1
)
Fig. 4. X-ray diffraction plots for (4-3,4,5-3,5) nG2-CH2-Boc-l-
Tyr-l- Ala-OMe (n = 12, 16) recorded at 95 and 98◦C in their
two-dimesional ꢀh lattice.
Conclusions
This publication reports the second example of dendritic
dipeptide that self-assembles in supramolecular porous
structures. The structures, together with the one reported
previously,[1] provide a new class of supramolecular poly-
mers. The change in the structure of the dendritic dipep-
tide from (4-3,4-3,5)12G2-CH2-Boc-l-Tyr-l-Ala-OMe to
(4-3,4,5-3,5)12G2-CH2-Boc-l-Tyr-l-Ala-OMe mediates a
reduction of the pore diameter. These experiments provide
the first example of pore size design by using a single dipep-
tide and different dendrons in the structure of the dendritic
dipeptide. These results open numerous synthetic strategies
for the design of supramolecular tubular polymers. The self-
assembled structures reported in this publication are comple-
mentary to concepts elaborated in other laboratories.[11–13]
This class of porous assemblies provides one of the few
examples of synthetic supramolecular architectures that
the hydrophobic dendron. The conformation of the (4-3,4,5-
3,5)16G2-CH2-Boc-l-Tyr-l-Ala-OMe in the supramolecular
structure from Fig. 6 is shown in Fig. 7a and compared
with the structure of (4-3,4-3,5)12G2-CH2-Boc-l-Tyr-l-Ala-
OMe (Fig. 7b).
The difference between the size of the two dendrons
observed from their top view projections explains the mech-
anism responsible for a reduced pore size in the case of
the supramolecular column generated from (4-3,4,5-3,5)
16G2-CH2-Boc-l-Tyr-l-Ala-OMe. The wider (4-3,4,5-
3,5)nG2-CH2- dendron (n = 12, 16) reduces the number of
dipeptides that is available to construct the pore in the
case of (4-3,4-3,5)12G2-CH2- dendron. This mechanism
can be visualized when the top views of the supramolec-
ular pores self-assembled from these two structures are

478
V. Percec et al.
exhibit tertiary and quaternary structures.[13] These tubular
supramolecular polymers complement other supramolecu-
lar concepts reported previously from our[14–18] and other
laboratories.[19,20]
(a)
95ꢃC
(b)
70ꢃC
100ꢃC
30ꢃC
j
i
m
k
k
l
l
(a)
(b)
Fibre axis
24ꢃC
j
m
m
k
l
l
ꢄ40ꢃC
n
n
k
k
l
l
Fig. 5. X-ray diffraction patterns of aligned fibre samples:
(a) (4-3,4,5-3,5)12G2-CH2-Boc-l-Tyr-l-Ala-OMe and (b) (4-3,4,5-
3,5)16G2-CH2-Boc-l-Tyr-l-Ala-OMe. Legend: i: short-range helical
feature (∼4.5 0.2 Å); j: tilt (∼62 5◦); k: registry along the column
axis (∼5 0.2 Å); l: (hk0) reflections of the p6mm columnar phase;
m: (hkl) crystal reflections; n: reflection of the aliphatic tails in the
glassy phase. The temperature at which the XRD scans were recorded
is indicated on each diffraction pattern.
Fig. 6. The structure of the supramolecular porous column
self-assembled from (4-3,4,5-3,5)16G2-CH2-Boc-l-Tyr-l-Ala-OMe.
(a) Side and top Van der Waals surface views of the supramolecular
column; for simplicity the aliphatic tails are not shown. (b) Cross-
section through the hydrophobic pore; the dendrons are shown up to the
phenyl groups of Tyr. Legend: Boc: blue; NH: green; O: red; C: grey;
H: white. Full colour is available in the electronic version of this paper.
(a)
(b)
Fig. 7. Side and top views of the dendritic dipeptides (alkyl groups from the periphery are not shown). (a) (4-3,4,5-3,5)nG2-CH2-Boc-l-Tyr-l-
Ala-OMe (n = 12, 16); (b) (4-3,4-3,5)12G2-CH2-Boc-l-Tyr-l-Ala-OMe.

Helical Porous Protein Mimics
479
(a)
(b)
Fig. 8. Single layer top views for the supramolecular columns self-assembled from (a) (4-3,4,5-3,5)nG2-CH2-Boc-l-Tyr-l-
Ala-OMe (n = 12, 16) and (b) (4-3,4-3,5)12G2-CH2-Boc-l-Tyr-l-Ala-OMe. Dotted yellow lines indicate the hydrogen-bonding
formation. The dipeptides from the next layer are shown in dark grey. Full colour is available in the electronic version of this paper.
(a)
(b)
(c)
(d)
H1
O2
N1
C1
O1
H2
C2
N2
(e)
(f)
(g)
C2
H2
N2
2.33
O2
2.30
2.07
1.69
2.09
2.49
2.43
1.79
2.47
1.96
1.88
H1
N1
O1
C1
Fig. 9. Supramolecular pore structure detail for (4-3,4,5-3,5)nG2-CH2-Boc-l-Tyr-l-Ala-OMe (n = 12, 16)—(a) side and (b) top views of the
pore region along for a 14-layer molecular model (structure shown up to the phenyl group of Tyr). Hydrogen-bonding network—(c) side, (d) top,
and (e) side views, only the H1–N1–C1–O1 and H2–N2–C2–O2 atoms (H green, N green, C grey, O red) of the dipeptide are shown. Hydrogen-
bonding detail—( f ) for (4-3,4-3,5)12G2-CH2-Boc-l-Tyr-l-Ala-OMe and (g) for (4-3,4,5-3,5)nG2-CH2-Boc-l-Tyr-l-Ala-OMe (n = 12, 16); only
the H atoms that participate to hydrogen bonds are shown, indicated bond lengths are in Ångström units. Full colour is available in the electronic
version of this paper.

480
V. Percec et al.
Experimental
following parameters: scanned optical range 210–320 nm, scan band
width 1 nm, scanning speed 100 nm min−1, response 1 s, accumulations
5, scanned thermal ranges 8–60◦C, 60–8◦C, and 8–60◦C, respectively
(data pitch 2◦C, temperature slope 1◦C min−1). Before starting the
experiment the sample was allowed to reach the 8◦C starting tem-
perature (∼10–15 min) but once started the three thermal cycles were
performed successively. Data were processed using Spectra Manager
ver. 1.51 software (Jasco).
Materials
Methyl 4-hydroxybenzoate (99%), 1-bromohexadecane (98%), and allyl
bromide (98%) were obtained from Lancaster Synthesis; thionyl chlo-
ride (99.5%), LiAlH4 (95%), and anhydrous K2CO3 were obtained from
Aldrich; methyl 3,4,5-trihydroxybenzoate (97%), 3,5-dihydroxybenzoic
acid (97%), palladium(ii) acetate (47.5% Pd), cyanuric chloride (99%),
1-bromododecane (98%), and triphenylphosphine (99%) were obtained
from Acros Organics; and Boc-l-Tyr-OH (99%), Boc-l-Tyr(OH)-OH
(99%), and H2N-l-Ala-OMe·HCl (99%) were obtained from Bachem
Peptides. 2,6-Di-tert-butyl-4-methylpyridine (DTBMP) was prepared
using a literature procedure.[21] 2-Chloro-4,6-dimethoxy-1,3,5-triazene
(CDMT) was obtained from cyanuric chloride following a literature
synthesis.[22] Acetone, N,N-dimethylformamide (DMF), ethyl acetate,
magnesium sulfate, and methanol (Fisher ACS reagents) and silica gel
(Sorbent Technology) were used as received. THF and dichloromethane
(Fisher ACS reagents) were refluxed over sodium/benzophenone and
CaH2, respectively, and freshly distilled before use. Cyclohexane for CD
experiments, dichloromethane for HPLC assays, and THF for MALDI-
TOF assignments were obtained from Fisher (HPLC grade). Deuterated
chloroform for NMR spectra was from Cambridge Isotope Laborato-
ries. All other chemicals were commercially available and were used as
received.
X-ray diffraction measurements were performed using CuKα1 radi-
ation (λ 1.54178 Å) from a rotating anode X-ray source (FR-591,
Bruker–Nonius) with a 0.2 × 0.2 mm2 filament operated at 3.4 kW. The
beam was collimated and focussed by a single bent mirror and sagitally
focussing Ge(111) monochromator, resulting in a 0.3 × 0.4 mm2 spot
on a multiwire area detector (Hi-Star, Bruker-AXS) 125 cm from the
sample. To minimize attenuation and background scattering, an integral
vacuum was maintained along the length of the flight tube and within
the sample chamber. Powder or aligned samples were held in quartz
capillaries (0.7–1.0 mm diameter), then mounted in a temperature con-
trolled oven (temperature precision 0.1◦C, temperature range −120
to 270◦C). Sample to multiwire area detector distances are 11.0 cm for
wide-angle diffraction experiments and 54.6 cm for intermediate angle
diffraction experiments. Aligned samples for fibre XRD experiments
were prepared using a custom-made extrusion device. The powdered
sample (∼10 mg) was heated inside the extrusion device to isotropic
transition temperature. After cooling slowly from the isotropic state,
the fibre was extruded in the mesophase and cooled to 23◦C. Typ-
ically the aligned samples have a thickness of ∼0.3–0.7 mm and a
length of ∼3–7 mm. All X-ray diffraction measurements were done
with the aligned sample axis perpendicular to the beam direction.
X-ray diffraction peaks position and intensity analysis was performed
using Datasqueeze ver. 20.1 software, that allows background elimina-
tion and Gaussian, Lorentzian, Lorentzian-squared, orVoigt peak-shape
fitting.
Techniques
The purity of the products was determined by a combination of TLC,
HPLC, 1H and 13C NMR, MALDI-TOF mass spectrometry, and ele-
mental analysis. TLC was carried on silica gel coated aluminum plates
(indicator F254, layer thickness 200 µm, particle size 2–25 µm, pore
size 60 Å, Sigma-Aldrich). HPLC was performed in dichloromethane
on a high-pressure liquid chromatograph (Series 10, Perkin–Elmer)
equipped with a LC-100 column oven, integrator data station (900,
NelsonAnalytical), and two gel columns of 5 × 102 and 104 Å pore size
(PL, Perkin–Elmer), using for detection the UV absorbance at 254 nm.
1H (500 MHz) and 13C (125 MHz) NMR spectra were recorded on a
DRX 500 instrument (Bruker).
Thermal transitions were measured on a modulated differential scan-
ning calorimeter (DSCQ100, TA Instruments). In all cases the heating
andthecoolingrateswere10◦C min−1.Thetransitiontemperatureswere
measured as the maxima and minima of their endothermic and exother-
mic peaks. Indium was used as calibration standard. A thermal optical
polarized microscope (BX51, 100× magnification, Olympus) equipped
with a hot stage (FP82HT, Mettler) and a central processor (FP90, Met-
tler Toledo) were used to verify thermal transitions and to characterize
anisotropic textures. Small parts of the aligned samples were heated
on the hot stage up to temperatures close, but always bellow isotropic
transition to avoid losing the sample alignment. After a short anneal-
ing, image acquisitions were performed. Density measurements were
carried out by floatation in gradient columns at 20◦C.
MALDI-TOF mass spectrometry was carried out on a mass spec-
trometer (Voyager-DE, PerSeptive Biosystems) operating in linear
mode. The spectrometer equipped with a nitrogen laser (337 nm) was
calibrated using the peptides angiotensin II and bombesin as standards.
The laser steps and voltages applied were adjusted depending on both
the molecular weight and the nature of each analyzed compound. Either
2,5-dihydroxybenzoic acid or 4-hydroxybenzylidenemalononitrile was
used as matrix. THF was used for dissolving both matrix and sample
(workingconcentrations:10 mg mL−1 forthematrixand5–10 mg mL−1
for the sample). The analytical sample was obtained by mixing sample
and matrix solutions in a 1:5 v/v ratio; 0.5 µL of this resulting solution
was loaded onto the MALDI plate and allowed to dry at 23◦C before
performing the analysis.
Circular dichroism (CD) spectra were recorded on a spectropho-
tometer (J-720, Jasco) equipped with a variable temperature circulator
(RTE-111, NESLAB). Each sample was dissolved in cyclohexane
(0.5 × 10−4 M) at 23◦C, then heated to 60◦C and allowed to cool at
23◦C when the solution remained homogenous. CD measurements were
performed using a 1-mL quartz cuvette of 0.1 cm path length and the
Molecular modelling simulations were performed using the Mate-
rials Studio Modelling ver. 3.1 software (Accelrys). The package’s
Discover module was used to perform the energy minimizations on the
supramolecular structures with the following settings: PCFF or COM-
PASS force fields, and Flechter–Reeves algorithm for the conjugate
gradient method.
Synthesis of Dendritic Dipeptides (4-3,4,5-3,5)nG2-CH2-Boc-L-Tyr-
L-Ala-OMe (n = 12, 16)
Compounds 2 and 5,[23] 3 and 6,[24] and 11[1] were synthesized
according to the procedures published from our laboratory.
[4-3,4,5]nG1CH2OH
To a 0◦C slurry of LAH (1.1 equiv.) in dry THF was added slowly
[4-3,4,5]nG1CO2CH3 (1 equiv.) in dryTHF. Upon addition, the mixture
was allowed to stir at 23◦C for 1 h, or until TLC (7:1 hexane/EtOAc)
showed completion. The reaction mixture was cooled to 0◦C and
quenched by slow successive addition of H2O (x mL per x g of LAH),
15% NaOH (x mL per x g of LAH), and H2O (3x mL per x g of LAH),
and stirring continued until H2 evolution ceased. The reaction mix-
ture was then filtered and the lithium salts were rinsed generously with
CH2Cl2. The filtrate was dried over MgSO4 and concentrated to give
the benzyl alcohol, which was taken to the next step without further
purification.
[4-3,4,5]12G1-CH2OH
White solid, 2.35 g (98%), mp 82–83◦C. δH (500 MHz, CDCl3) 7.32
(d, 4H, J 8.8), 7.27 (d, 2H, J 8.6), 6.89 (d, 4H, J 8.6), 6.76 (d, 2H,
J 8.6 Hz), 6.65 (s, 2H), 5.01 (s, 4H), 4.93 (s, 2H), 4.57 (s, 2H), 3.94
(m, 6H), 1.78 (m, 6H), 1.45 (m, 6H), 1.39–1.21 (m, 48H), 0.88 (t, 9H,
J 6.8 Hz). δC (125 MHz, CDCl3) 158.9, 153.0, 130.2, 129.1, 114.4,
114.1, 106.6, 74.8, 71.0, 68.0, 67.9, 65.4, 31.9, 29.7, 29.6, 29.4, 29.3
(×2), 26.1, 22.7, 14.1. Found: C 78.4, H 10.1. Calc. for C64H98O7:
C 78.5, H 10.1%.

Helical Porous Protein Mimics
481
[4-3,4,5]16G1-CH2OH
(m, 1H), 5.38 (m, 1H), 5.28 (m, 1H), 5.26 (m, 1H), 4.50 (m, 4H), 4.48
(s, 2H). δC (125 MHz, CDCl3) 159.8, 139.4, 132.9, 117.7, 107.4, 101.8,
68.9, 46.2. Found: C 65.4, H 6.3. Calc. for C13H15ClO2: C 65.4, H 6.3%.
White solid, 1.02 g (99%), mp 80◦C. δH (500 MHz, CDCl3) 7.31
(d, 4H, J 9.0 Hz), 7.27 (d, 2H, J 9.0 Hz), 6.87 (d, 4H, J 9.0), 6.75 (d,
2H, J 9.0), 6.64 (s, 2H), 5.00 (s, 4H), 4.93 (s, 2H), 4.55 (d, 2H, J 5.5),
3.95 (t, 4H, J 6.5), 3.91 (t, 2H, J 6.5), 1.81–1.71 (m, 6H), 1.48–1.41
(m, 6H), 1.39–1.22 (m, 72H), 0.88 (t, 9H, J 7.0). δC (125 MHz, CDCl3)
158.9, 153.0, 137.8, 136.4, 130.2, 129.9, 114.4, 114.1, 106.6, 74.8, 71.0,
68.0, 67.9, 65.4, 31.9, 29.7, 29.6 (×2), 29.4, 29.3 (×2), 26.1, 22.7, 14.1.
Found: C 79.5, H 10.7. Calc. for C76H122O7: C 79.5, H 10.7%.
[3,5]AllylG1-CH2-Boc-L-Tyr-L-Ala-OMe 12
Boc-l-Tyr(OH)-l-Ala-OMe 11 (200 mg, 0.546 mmol) was added to
a degassed suspension of K2CO3 (226 mg, 1.64 mmol) in DMF (10 mL)
and heated to 70◦C, then 3,5-diallyloxybenzyl chloride (11) (143 mg,
0.600 mmol) was added. The reaction mixture was stirred overnight at
70◦C, cooled to 23◦C and taken up in EtOAc, washed with water (5×),
brine, dried over MgSO4, and concentrated under reduced pressure.
The crude product was purified by flash column chromatography: silica
gel/2% MeOH in CH2Cl2 to give 210.5 mg (68%) of the [3,5]allyl-G1-
CH2Boc-l-Tyr-l-Ala-OMe 12 as a yellowish oil. δH (500 MHz, CDCl3)
7.10 (d, 2H, J 8.5), 6.88 (d, 2H, J 8.5), 6.59 (m, 2H), 6.44 (m, 1H), 6.37
(d, 1H, J 2.5), 6.07–5.99 (m, 2H), 5.41 (m, 1H), 5.38 (m, 1H), 5.28 (m,
1H), 5.26 (m, 1H), 4.96 (s, 3H), 4.51 (d, 2H, J 5.5), 4.29 (s, 1H), 3.71 (s,
3H), 3.07–2.96 (m, 2H), 1.42 (s, 9H), 1.34 (d, 3H, J 7.0). δC (125 MHz,
CDCl3) 172.8, 170.7, 159.9, 139.4, 133.1, 130.4, 117.7, 115.1, 106.1,
101.3, 69.9, 68.9, 52.4, 48.1, 37.4, 28.2, 18.4. Found: C 65.5, H 7.1,
N 4.9. Calc. for C31H40N2O8: C 65.5, H 7.1, N 4.9%.
[4-3,4,5]nG1-CH2Cl (n = 12, 16)
To a solution of [4-3,4,5]nG1-CH2OH (n = 12, 16) (1 equiv.) and
DTBMP (1.5 equiv.) in dry CH2Cl2 was added slowly SOCl2 (1.1 equiv.)
and the reaction allowed to stir at 23◦C for 5 min. TLC analysis (7:1
Hex:EtOAc) showed completion. Solvent was removed under reduced
pressure and the residue was recrystallized from acetone to give the
benzyl chlorides 7 and 8, which decomposed upon melting.
[4-3,4,5]12G1-CH2Cl 7
Off-white solid, 3.77 g (95%). δH (500 MHz, CDCl3) 7.33 (d, 4H, J
8.8), 7.28 (d, 2H, J 8.3), 6.90 (d, 4H, J 8.6), 6.77 (d, 2H, J 8.6), 6.68 (s,
2H), 3.97 (t, 4H, J 6.6), 3.93 (t, 2H, J 6.6), 1.79 (m, 6H), 1.46 (m, 6H),
1.40–1.21 (m, 48H), 0.89 (t, 9H, J 6.8). δC (125 MHz, CDCl3) 158.9,
153.0, 138.6, 132.6, 130.2, 129.7, 129.2, 128.8, 114.4, 114.1, 108.4,
74.8, 71.1, 68.0 (×2), 46.8, 31.9, 29.7, 29.6 (×2), 29.4, 29.3 (×2), 26.1,
22.7, 14.1. Found: C 77.0, H 9.8. Calc. for C64H97ClO6: C 77.0, H 9.8%.
[3,5]OHG1-CH2-Boc-L-Tyr-L-Ala-OMe 13
Palladium(ii) acetate (4 mg, 0.018 mmol) was added to a thor-
oughly degassed solution of [3,5]allylG1-CH2Boc-l-Tyr-l-Ala-OMe 12
(210 mg, 0.369 mmol), PPh3 (24 mg, 0.092 mmol), and Et3NHCO2H
(164 mg, 1.11 mmol) in EtOH (20 mL). The reaction mixture was
refluxed overnight, cooled to room temperature and then taken up in
EtOAc, washed with water (3×), brine, dried over MgSO4, and con-
centrated under reduced pressure. The crude product was purified by
flash column chromatography (silica gel/5% MeOH in CH2Cl2) to give
124.5 mg (70%) of [3,5]OHG1-CH2Boc-l-Tyr-l-Ala-OMe 13 as off-
white crystals. δH (500 MHz, CDCl3) 6.96 (br s, 4H), 6.75 (d, 2H, J 9),
6.65 (s, 1H), 6.41 (s, 2H), 6.32 (s, 1H), 5.21 (br s, 1H), 4.84 (s, 2H),
4.48 (m, 1H), 4.27 (br s, 1H), 3.66 (s, 3H), 2.91 (m, 2H), 1.29 (d, 3H,
J 7.0). δC (125 MHz, CDCl3) 172.8, 170.8, 157.9, 137.0, 130.4, 128.5,
127.4, 115.0, 70.0, 52.3, 48.0, 37.4, 33.9, 28.2, 18.3. Found: C 61.5,
H 6.6, N 5.7. Calc. for C25H32N2O8: C 61.5, H 6.6, N 5.7%.
[4-3,4,5]16G1-CH2Cl 8
Off-white solid, 2.59 g (89%). δH (500 MHz, CDCl3) 7.31 (d, 4H, J
8.5), 7.26 (d, 2H, J 8.5), 6.88 (d, 4H, J 8.5), 6.75 (d, 2H, J 8.5), 6.67 (s,
2H), 5.01 (s, 4H), 4.93 (s, 2H), 4.48 (s, 2H), 3.96 (t, 4H, J 6.5), 3.92 (t,
2H, J 6.5), 1.80–1.71 (m, 6H), 1.48–1.40 (m, 6H), 1.38–1.20 (m, 72H),
0.88 (t, 9H, J 7.0). δC (125 MHz, CDCl3) 158.9, 153.0, 137.8, 130.2,
129.9, 114.4, 114.1, 106.6, 74.8, 71.0, 68.0, 67.9, 65.4, 31.9, 29.7, 29.6
(×2), 29.4, 29.3 (×2), 26.1, 22.7, 14.1. Found: C 78.3, H 10.4. Calc. for
C76H121ClO6: C 78.3, H 10.5%.
3,5-Diallyloxybenzyl Chloride 10
A mixture of methyl 3,5-dihydroxybenzoate (1.00 g, 5.95 mmol),
K2CO3 (2.46 g, 17.8 mmol) and allyl bromide (1.44 g, 11.9 mmol) in
acetone (80 mL) was refluxed under argon for 4 h. TLC analysis (5%
MeOH in CH2Cl2) showed completion of reaction. After cooling to
23◦C, the reaction mixture was partitioned between ethyl acetate and
water. The organic phase was washed with water (3×), dried over
MgSO4, and concentrated under reduced pressure. The crude product
was passed through a silica plug eluted with 7:1 hexane/EtOAc to give
the methyl 3,5-diallyloxybenzoate as a clear oil which was taken up in
dry THF (15 mL) and added slowly to a suspension of LAH (250 mg,
6.55 mmol) in dry THF (10 mL). After stirring for 30 min at 23◦C,
TLC analysis (7:1 hexane/EtOAc) showed completion. Reaction was
quenched by slow successive addition of water (250 µL), followed by
15% aqueous NaOH (250 µL), and water (750 µL). Stirring was con-
tinued until H2 evolution ceased, and the resulting lithium salts were
filtered off and rinsed generously with CH2Cl2, the filtrate was dried
over MgSO4, and concentrated under reduced pressure to give 1.20 g
(92% over two steps) of the diallyloxybenzyl alcohol. This diallyloxy-
benzyl alcohol (1.20 g, 5.45 mmol) was taken up in dry CH2Cl2 (40 mL)
and a catalytic amount of DMF added.To this solution was slowly added
SOCl2 (707 mg, 5.99 mmol), and the reaction was stirred at 23◦C for
5 min after which TLC analysis (7:1 hexane/EtOAc) showed comple-
tion. The reaction mixture was diluted with CH2Cl2 and quenched by
slow addition of water. The phases were separated and the organic phase
was washed with water (1×) and saturated aqueous NaHCO3 (2×). The
organic phase was dried over MgSO4 and concentrated under reduced
pressure to give 1.20 g (92%) of 3,5-diallyloxybenzyl chloride 10 as a
yellow oil, which was used without further purification. δH (500 MHz,
CDCl3) 6.54 (d, 2H, J 2.5), 6.44 (t, 1H, J 2), 6.06–5.99 (m, 2H), 5.41
[4-3,4,5-3,5]nG2-CH2-Boc-L-Tyr-L-Ala-OMe (n = 12, 16)
[3,5]OHG1-CH2-Boc-l-Tyr-l-Ala-OMe 13 (1 equiv.) was added to a
thoroughlydegassedsuspensionofK2CO3 (3equiv.)inDMF.Theresult-
ing mixture was heated to 70◦C, at which point the tri-substituted benzyl
chloride 7 or 8 (2 equiv.) was added. The reaction was stirred at 70◦C
overnight, cooled to 23◦C and the product was precipitated into water,
collected by suction filtration, air dried, and purified by flash column
chromatography (silica gel/1% MeOH in CH2Cl2) followed by precip-
itation in MeOH from minimal CH2Cl2 to give dendritic dipeptides 14
or 15 as off-white solid.
[4-3,4,5-3,5]12G2-CH2-Boc-L-Tyr-L-Ala-OMe 14
Off-white solid, 120 mg (61%). mp 96–98◦C, [α]D20 −8.3 (c
0.05 in THF). m/z (MALDI-TOF) for C153H224N2O20 calc. 2434.41
[M + Na+]; found 2434.43. HPLC > 99% pure. δH (500 MHz, CDCl3)
7.30 (d, 8H, J 8.5), 7.27 (d, 4H, J 8.5), 7.11 (d, 2H, J 8.5), 6.90 (d, 2H,
J 8.5), 6.86 (d, 8H, J 8.5), 6.75 (d, 4H, J 8.5), 6.73 (s, 4H), 6.68 (m,
2H), 6.56 (m, 1H), 6.34 (d, 1H, J 7.0), 5.00 (s, 8H), 4.97 (s, 2H), 4.91
(d, 8H, J 3.5), 4.51 (m, 1H), 4.25 (br s, 1H), 3.96–3.90 (m, 12H), 3.69
(s, 3H), 3.05–2.94 (m, 2H), 1.80–1.72 (m, 12H), 1.45 (m, 12H), 1.41 (s,
9H), 1.34 (d, 3H, J 7.0), 1.33–1.20 (m, 96H), 0.88 (t, 18H, J 6.5). δC
(125 MHz, CDCl3) 170.7, 160.2, 159.0 (×2), 149.4, 149.1, 139.4, 130.4
(×2), 130.1, 129.2, 129.1, 129.0, 121.0, 115.5, 115.1, 114.5, 106.4,
101.5, 71.4, 71.3, 70.1, 70.0, 68.1, 52.4, 48.1, 31.9, 29.7, 29.6, 29.4,
29.3, 28.3, 26.1, 22.7, 18.4, 14.1. Found: C 76.2, H 9.3, N 1.2%. Calc.
for C153H224N2O20: C 76.2, H 9.4, N 1.2%.

482
V. Percec et al.
[4-3,4,5-3,5]16G2-CH2-Boc-L-Tyr-L-Ala-OMe 15
Off-white solid, 105 mg (60%). mp 119–120◦C, [α]D20 −7.9 (c
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0.05 in THF). m/z (MALDI-TOF) for C177H272N2O20 calc. 2771.05
[M + Na+]; found 2771.04. HPLC > 99% pure. δH (500 MHz, CDCl3)
7.31 (d, 8H, J 8.0), 7.26 (d, 4H, J 8.0), 7.10 (d, 2H, J 8.0), 6.91 (d,
2H, J 8.0), 6.86 (d, 8H, J 8.0), 6.77 (d, 4H, J 8.0), 6.73 (s, 4H), 6.68
(m, 2H), 6.55 (m, 1H), 6.35 (d, 1H, J 7.0), 5.00 (s, 8H), 4.97 (s, 2H),
4.91 (d, 8H, J 3.5), 4.51 (m, 1H), 4.25 (br s, 1H), 3.96–3.90 (m, 12H),
3.69 (s, 3H), 3.06–2.94 (m, 2H), 1.80–1.72 (m, 12H), 1.45 (m, 12H),
1.41 (s, 9H), 1.34 (d, 3H, J 7.0), 1.32–1.20 (m, 144H), 0.88 (t, 18H,
J 7.0). δC (125 MHz, CDCl3) 170.7, 160.2, 159.0 (×2), 149.4, 149.1,
139.4, 130.4 (×2), 130.1, 129.2, 129.1 (×2), 129.0, 121.0, 115.6, 115.1,
114.5, 106.4, 101.5, 71.4 (×2), 70.1, 70.0, 68.1, 52.4, 48.1, 31.9, 29.7,
29.6 (×2), 29.4, 29.3 (×2), 28.3, 26.1, 22.7, 18.4, 14.1. Found: C 77.38,
H 10.0, N 1.0. Calc. for C177H272N2O20: C 77.4, H 10.0, N 1.0%.
Acknowledgments
Financial support by the National Science Foundation (DMR-
9996288 and DMR-0102459) and the Office of Naval
Research is gratefully acknowledged.
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299, 1208. doi:10.1126/SCIENCE.1078849
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