Sequence-defined dendrons dictate supramolecular cogwheel assembly of dendronized perylene bisimides

Article abstract of DOI:10.1021/jacs.9b08714

A dendronized perylene bisimide (PBI) that self-organizes into hexagonal arrays of supramolecular double helices with identical single crystal-like order that disregards chirality was recently reported. A cogwheel model of selfassembly that explains this process was proposed. Accessing the highly ordered cogwheel phase required very slow heating and cooling or extended periods of annealing. Analogous PBIs with linear alkyl chains did not exhibit the cogwheel assembly. Here a library of sequence-defined dendrons containing all possible compositions of linear and racemic alkyl chains was employed to construct self-assembling PBIs. Thermal and structural analysis of their assemblies by differential scanning calorimetry (DSC) and fiber X-ray diffraction (XRD) revealed that the incorporation of n-alkyl chains accelerates the formation of the high order cogwheel phase, rendering the previously invisible phase accessible under standard heating and cooling rates. Small changes to the primary structure, as constitutional isomerism, result in significant changes to macroscopic properties such as melting of the periodic array. This study demonstrated how changes to the sequencedefined primary structure, including the relocation of methyl groups between two constitutional isomers, dictate tertiary and quaternary structure in hierarchical assemblies. This led to the discovery of a sequence that self-organizes the cogwheel assembly much faster than even the corresponding homochiral compounds and demonstrated that defined-sequence, which has long been recognized as determinant for the complex structure of biomacromolecules including proteins and nucleic acids plays the same role also in supramolecular synthetic systems.

Full text of DOI:10.1021/jacs.9b08714

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Communication
Sequence-Defined Dendrons Dictate Supramolecular
Cogwheel Assembly of Dendronized Perylene Bisimides
Benjamin E. Partridge, Li Wang, Dipankar Sahoo, James T Olsen, Pawaret
Leowanawat, Cecile Roche, Henrique Ferreira, Kevin J Reilly, Xiangbing Zeng,
Goran Ungar, Paul A. Heiney, Robert Graf, Hans W. Spiess, and Virgil Percec
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b08714 • Publication Date (Web): 18 Sep 2019
Downloaded from pubs.acs.org on September 18, 2019
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Sequence-Defined Dendrons Dictate Supramolecular Cogwheel
Assembly of Dendronized Perylene Bisimides
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Benjamin E. Partridge,†, □ Li Wang,†,‡ Dipankar Sahoo,† James T. Olsen,† Pawaret Leowanawat,†,○
Cecilé Roche,† Henrique Ferreira,† Kevin J. Reilly,† Xiangbing Zeng,§ Goran Ungar,§,⊥ Paul A.
Heiney,# Robert Graf, ◊ Hans W. Spiess,◊ and Virgil Percec†,*
† Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia,
Pennsylvania 19104-6323, United States
‡ College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China.
§ Department of Materials Science and Engineering, University of Sheffield, Sheffield, S1 3JD, United Kingdom
⊥ State Key Laboratory for Mechanical Behavior of Materials, Xi’an Jiaotong University, Xi’an 710049, China
# Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6396,
United States
◊ Max-Planck Institute for Polymer Research, 55128 Mainz, Germany
Supporting Information Placeholder
defined primary structure, including the relocation
of methyl groups between two constitutional
isomers, dictate tertiary and quaternary structure in
hierarchical assemblies. This led to the discovery of
a sequence that self-organizes the cogwheel
assembly much faster than even the corresponding
homochiral compounds and demonstrated that
defined-sequence, which has long been recognized
as determinant for the complex structure of
biomacromolecules including proteins and nucleic
acids plays the same role also in supramolecular
synthetic systems.
ABSTRACT: A dendronized perylene bisimide (PBI)
that self-organizes into hexagonal arrays of
supramolecular double helices with identical single
crystal-like order that disregards chirality was
recently reported. A cogwheel model of self-
assembly that explains this process was proposed.
Accessing the highly ordered cogwheel phase
required very slow heating and cooling or extended
periods of annealing. Analogous PBIs with linear
alkyl chains did not exhibit the cogwheel assembly.
Here a library of sequence-defined dendrons
containing all possible compositions of linear and
racemic alkyl chains was employed to construct
self-assembling PBIs. Thermal and structural
analysis of their assemblies by differential scanning
calorimetry (DSC) and fiber X-ray diffraction (XRD)
revealed that the incorporation of n-alkyl chains
accelerates the formation of the high order
cogwheel phase, rendering the previously invisible
phase accessible under standard heating and
cooling rates. Small changes to the primary
structure, as constitutional isomerism, result in
significant changes to macroscopic properties such
as melting of the periodic array. This study
demonstrated how changes to the sequence-
Function relies on hierarchical transfer of
structural information from individual building
blocks
to
supramolecular
structure.
Biomacromolecules such as proteins1 and nucleic
acids2 require homochiral building blocks arranged
in a defined-sequence with monodisperse chain
length. In poly(propylene), the stereochemistry of
methyl groups mediates function even with
polydisperse chains.3 This strategy to highly
ordered structures and functions endows the
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demand for homochirality, defined-sequence and
1
2
monodisperse chains in biomacromolecules.4
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FIGURE 1. Cogwheel model of self-assembly.7 (a) Molecular structure of rrr-PBI. Chiral methyl group indicated in
pink. (b) Two crystalline columnar hexagonal phases (Φhk1, Φhk2) are generated via hierarchical self-assembly of
dimers rotated around the column axis. (c) Formation of a hexagonal crystalline array with only one helical column
in the unit cell drives deracemization between columns. (d) Key aspects of the cogwheel model.
SCHEME 1. Synthesis of PBIs with Sequence-Defined Linear Racemic Hybrid Minidendronsa
a
Reagents and conditions: (i) BnCl, K2CO3, KI, acetone, reflux, 18 h; (ii) RBr, K2CO3, DMF, 120 °C, 3.5 h; (iii) H2,
Pd/C, CH2Cl2, MeOH, 23 °C, 24 h; (iv) triethyl orthoformate, Amberlyst-15(H), toluene, reflux, 18 h; (v) RBr, K2CO3,
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DMF, 65–70 °C, 4–7 h; (vi) 2M HCl, methanol, 23 °C, 7 h; (vii) LiAlH4, THF, 23 °C, 1 h; (viii) SOCl2, cat. DMF, 23 °C,
CH2Cl2, 0.5 h; (ix) NaN3, DMF, 23 °C, 9 h; (x) PTCDA, Zn(OAc)2∙2H2O, quinoline, 180 °C, 6 h.
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FIGURE 2. DSC traces of PBIs with hybrid dm8*/C8 dendrons measured upon heating the as-prepared sample at
10 °C/min. Phases determined by XRD, transition temperatures (in °C), and associated enthalpy changes (in
k1
parentheses, in kcal/mol) are indicated. Phase notation: Φh – columnar hexagonal crystal with offset dimers5;
Φhk2 – columnar hexagonal crystal with cogwheel assembly5; Φc–ok – columnar centered orthorhombic crystal; Φs–
k
k
io
– columnar simple orthorhombic crystal; Φm – columnar monoclinic crystal; Φh – 2D columnar hexagonal
o
phase with short range intracolumnar order; i – isotropic.
Contrary to this expectation, a perylene bisimide
(PBI) containing two chiral minidendrons (Figure 1a)
was recently reported to form columnar hexagonal
into single-handed homochiral crystal domains
(Figure 1c), even for fully racemic samples such as
rrr-PBI (Figure 1a). This cogwheel model has three
key features (Figure 1d): (1) the length of the
extended alkyl chains is equal to the helical half-
pitch, ensuring the column periphery is covered in
alkyl chains to maximize intercolumnar van der
Waals interactions (Figure 1b); (2) the alkyl chains
lie parallel to the column axis, limiting
interdigitation of neighboring columns; (3) the
chiral methyl group on the dimethyloctyl (dm8*)
chain points towards the column center, hiding the
chirality of the stereocenter from the column
periphery and thus eliminating its role in
determining intercolumnar chiral interactions. This
cogwheel model was not observed in PBI
assemblies containing linear n-alkyl chains of any
length.9 This model (Figure 1),5 does not predict the
outcome of the replacement of dm8* with n-octyl
to the self-organization of PBIs. This raises the
simple question: how will PBIs with mixtures of
linear and branched alkyl chains assemble?
Answering this question is expected to provide
valuable insights and to broaden the scope of the
cogwheel model in self-assembly.
assemblies
with
single-crystal-like
order
irrespective of stereochemistry.5 This contrasts
examples6–8 where degree of order of 3D
assemblies is determined by stereochemical purity.
These enantiopure, racemic, and a mixture of 21
diastereomeric dendronized PBIs self-organized
k
into two distinct columnar hexagonal (Φh )
k1
crystalline arrays (Figure 1b), low order Φh with
PBI dimers stacked with 90° relative rotation and
translated away from the column center, and high
k2
order Φh with dimers along the column axis,
giving a smooth column exterior which enables
k2
ordered packing. The Φh was not observed at
heating or cooling rates of 10 °C/min but required
slow heating with 1 °C/min and was accidentally
discovered by fiber XRD experiments while
annealing the Φhk1 phase.
To rationalize this chirality-invariant crystallization
of columns in Φhk2, a cogwheel model that displays
the alkyl chains of the PBI dendrons as “teeth” on a
cogwheel, was proposed.5 These columns organize
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Sequence-defined structures10 are fundamental
to biomolecules11 and have also been employed in
self-assembling building blocks to assess protein-
carbohydrate binding on biological cell membrane
mimics.12 Here, four dendronized PBIs with defined-
sequences of n-octyl (also denoted 8 or C8) and
branched dm8* chains (r or rac) on a (3,4,5)-
minidendron were synthesized by iterative
methodologies (Scheme 1). These compounds are
identified by the placement of their chains in the 3-,
4-, and 5-positions: fully branched racemic rrr-PBI,
fully linear 888-PBI, symmetric hybrid r8r-PBI and
8r8-PBI, and nonsymmetric hybrid rr8-PBI and
88r-PBI. r8r-PBI is the constitutional isomer of rr8-
PBI while 8r8-PBI of 88r-PBI.
does not self-organize into the Φh phase (Figure
k2
1
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4
5
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2, top), all four hybrid PBIs with dm8* and C8 chains
k2
self-organize into the cogwheel Φh upon heating
and cooling at 10 °C/min (Figure 2). This dramatic
increase in rate of cogwheel assembly via the
sequence-defined dendrons suggests that the
k2
linear chains dictate the formation of the Φh
phase, which is the thermodynamically favored but
kinetically disfavored phase of rrr-PBI below 128–
130 °C.
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k2
The Φh of the four hybrid PBIs undergoes a
transition upon heating. Hybrid PBIs with two dm8*
chains (r8r- and rr8-PBI) form the Φh phase at
k1
152 and 146 °C, respectively, similar to rrr-PBI. By
contrast, hybrid PBIs with two n-octyls (8r8- and
88r-PBI) generate orthorhombic and 2D hexagonal
phases upon heating, similar to 888-PBI. Therefore,
the majority chain dictates the supramolecular
structure generated by the hybrid PBIs: dendrons
with more dm8* chains, r8r-, rr8-PBI, self-organize
identical phases as rrr-PBI and are sequences of
interest for physical investigations, whereas
dendrons with more n-octyls self-organize into
Iterative methodologies were employed to
construct the sequence of alkyl chains. Symmetric
hybrid minidendrons were prepared from 2,
obtained via benzylation of methyl gallate (1).13
Reaction of 1 with triethyl orthoformate gave
nonsymmetric acetal-protected 6,14 which was
employed for nonsymmetric dendrons. Alkylation
of 2 and 6, followed by deprotection, and
additional alkylation provided sequence-defined
similar phases to 888-PBI. Upon cooling all four
1
k2
dendrons 5. H and 13C NMR, MALDI-TOF mass
hybrids reform Φh
.
spectrometry, and HPLC confirmed the sequence-
defined structure of dendrons 5 (Figures S1–S20).
The isotropization temperatures (Ti) of the hybrid
PBIs depend on the number of linear chains and
the nature of the chain in the 4-position of the
dendron. Dendrons with 4-dm8* exhibit Ti values
similar to rrr-PBI (Ti of rrr-, rr8-, and 8r8-PBI =
200, 205, 209 °C) whereas those with an n-octyl in
the 4-position exhibit Ti values more similar to 888-
PBI (Ti of r8r-, 88r-, and 888-PBI = 223, 228, 229
°C). It is notable that Ti, which is indicative of
quaternary structure, differs by almost 20 °C
between constitutionally isomeric hybrid PBIs (red
boxes in Figure 2) and spans 30 °C across this entire
set of very similar primary structures.
All benzyl esters
5
hybrid dendrons were
subsequently converted to benzyl amines 12.
Imidation of perylene tetracarboxylic dianhydride
(PTCDA) with 12 and Zn(OAc)2∙2H2O in quinoline9a
afforded 8r8-, r8r-, rr8-, and 88r-PBI.
The thermal behavior of the six dendronized PBIs,
four sequence-defined hybrids plus rrr- and 888-
PBI, was measured by DSC with 10 °C/min (Figure
2, Figure S21). Phases were determined by fiber
XRD. As already reported,5 rrr-PBI assembles into a
highly ordered 3D columnar hexagonal phase by
the cogwheel model, denoted Φhk2. This phase was
not observed at 10 °C/min but required either
heating with 1 °C/min or annealing at 100 °C for
3 h and cooling (Figure 2).5 Only the columnar
hexagonal phase, Φhk1, was observed in the as-
prepared sample upon heating and cooling rrr-PBI
at 10 °C/min. The Φhk2 phase, formed by annealing,
Oriented fiber XRD was used to elucidate the
structures of hybrid PBI assemblies.15 Fiber XRD
patterns of rrr-PBI (Figure S22a) and the four
hybrid PBIs (Figure S22b–e) are consistent with the
k2
cogwheel Φh
phase (Table ST2). Lattice
k2
parameters of the Φh unit cell of these five PBIs
are identical, a = 26.7 ± 0.4 Å and c = 14.8 ± 0.1 Å.
Experimental densities of the PBIs range from 1.05
g/cm3 to 1.07 g/cm3 (Table ST3), and the calculated
number of molecules per column stratum, µ, is
0.97–1.08, that is, 1 molecule. The distance between
k1
undergoes a transition to the Φh phase at 128–
130 °C upon heating (Figure S1).5
By contrast to rrr-PBI, which requires annealing
k2
to generate the Φh phase, and to 888-PBI, which
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k2
strata, which corresponds to the average π–π
stacking distance, is 3.7 ± 0.05 Å, and the column
diameter (Dcol = a) is 26.7 ± 0.4 Å. The phases of
888-PBI have been reported.9c At 80 °C 888-PBI
exhibits a Φc–o phase with Dcol = 24.2 Å, µ = 1.01,
and a π–π distance of 3.6 Å (Figure S22f).
provides only the Φh after 3 h (Figure 3c). In
1
2
3
4
5
6
k2
contrast, heating the hybrid PBIs generates Φh
immediately at 100 °C, as shown for rr8-PBI in
Figure 3e. Further annealing at 100 °C does not
change the XRD pattern (Figure 3f), supporting that
k
k2
the ordered Φh is fully generated within minutes
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8
9
(Figure 3e). This dramatic enhancement of the rate
of formation of the Φhk2 in hybrid PBIs could not be
predicted and suggests that the linear alkyl chains
dictate ordering of the branched dm8* chains to
generate the cogwheel system. This thermal
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k2
behavior (Figure 2) suggests that the Φh of rrr-
PBI and the four hybrid PBIs cannot be strictly
identical, contrary to the highly similar lattice
parameters determined by XRD (Figure S22 and
Table ST2).
Solid state NMR reveals information about
dynamics on a timescale much longer than XRD.16
13C Cross-polarization magic angle spinning NMR
experiments of the hybrid PBIs (Figure S23) show
only subtle differences for signals corresponding to
C=O, the dendron phenyl ring, and –NCH2–,
suggesting that the packing of the dendron and
stacking of the PBI core are almost identical,
consistent with XRD data. Hence differences
between the supramolecular packing of the four
hybrid PBIs are driven mostly by the conformations
of the n-alkyl chains. NMR suggests that n-alkyls in
m- and p-positions increase local mobility at the
stereogenic center, providing faster crystallization
(Figure S23). Therefore, disorder creates order.4a,b
Modeling of similar supramolecular assemblies
does not typically consider the structure of the
aliphatic region.9,17 Demonstration of a hat-shaped
cyclotriveratrylene that undergoes supramolecular
deracemization provides a rare example of the n-
alkyl conformation being elucidated.6c A detailed
cogwheel model that accounts for n-alkyl
conformation is under investigation.
k2
FIGURE 3. Formation of Φh upon heating. (a–c) XRD
patterns of rrr-PBI recorded at (a) 25 °C after 5 min
and (b,c) 100 °C after (b) 60 min and (c) 180 min. (d–f)
XRD patterns of rr8-PBI recorded at (d) 25 °C after 5
min and (e,f) 100 °C after (e) 5 min and (f) 30 min.
Fiber axis indicated. Data collection time for each
pattern was 5 min, and hence data collection of (e)
started as soon as the sample reached 100 °C.
The cogwheel model enables the generation of
identical, highly ordered helical hexagonal crystals
that disregard chirality. This work demonstrated
that incorporation of n-alkyls into dendronized PBIs
with chiral racemic chains transforms the invisible
XRD demonstrates the enhanced rate of
k2
formation of the cogwheel Φh in hybrid PBIs
k2
cogwheel Φh into a kinetically accessible, visible
compared to rrr-PBI (Figure 3). Heating the Φhk1 of
rrr-PBI to 100 °C at 10 °C/min does not generate
high order Φhk2. After annealing at 100 °C for 60
phase, via a sequence-defined dendron. The
composition and the sequence of the dendrons in
hybrid linear-racemic PBIs dictates significant
differences in their thermal behavior, even between
k1
k2
min, coexistence of the Φh and Φh is observed
by XRD (Figure 3b). Continued annealing at 100 °C
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Search for the Laws of Self-Organization and Complexity; Oxford
constitutional isomers. This demonstrates that very
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of a building block dictates substantial changes to
macroscopic functions.
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ASSOCIATED CONTENT
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Roche, C.; Sun, H.-J.; Leowanawat, P.; Araoka, F.;
Supporting
Information.
The
Supporting
Partridge, B. E.; Peterca, M.; Wilson, D. A.; Prendergast, M. E.;
Heiney, P. A.; Graf, R.; Spiess, H. W.; Zeng, X.; Ungar, G.; Percec,
V. A Supramolecular Helix That Disregards Chirality. Nat. Chem.
2016, 8, 80–89.
Information is available free of charge on the ACS
9
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at DOI:
website.
(PDF)
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AUTHOR INFORMATION
Corresponding Author
*percec@sas.upenn.edu
Present Addresses
□
B.E.P.: Department of Chemistry and International
Institute of Nanotechnology, Northwestern University,
Evanston, Illinois 60208, United States
○
P.L.: Department of Chemistry and Center of
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Excellence for Innovation in Chemistry, Mahidol
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Field Guide to Foldamers. Chem. Rev. 2011, 101, 3893–4012.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
Financial support by the National Science Foundation
(DMR-1066116 and DMR-1807127 (V.P.), DMR-
1120901 (V.P. and P.A.H.)), the Humboldt Foundation
(V.P.) and the P. Roy Vagelos Chair at Penn (V.P.) is
gratefully acknowledged. B.E.P. thanks the Howard
Hughes Medical Institute for an International Student
Research Fellowship.
(8)
(a) Venkata Rao, K.; Miyajima, D.; Nihonyanagi, A.;
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