Pathway Complexity Versus Hierarchical Self-Assembly in N-Annulated Perylenes: Structural Effects in Seeded Supramolecular Polymerization

Article abstract of DOI:10.1002/anie.201801575

Studies were carried out on the hierarchical self-assembly versus pathway complexity of N-annulated perylenes 1–3, which differ only in the nature of the linking groups connecting the perylene core and the side alkoxy chains. Despite the structural simila

Full text of DOI:10.1002/anie.201801575

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Accepted Article
Title: Pathway complexity versus hierarchical self-assembly in N-
annulated perylenes. Structural effects in seeded supramolecular
polymerization
Authors: Elisa E. Greciano, Beatriz Matarranz, and Luis - Sanchez
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201801575
Angew. Chem. 10.1002/ange.201801575
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10.1002/anie.201801575
Angewandte Chemie International Edition
COMMUNICATION
Pathway complexity versus hierarchical self-assembly in N-
annulated perylenes. Structural effects in seeded supramolecular
polymerization
Elisa E. Greciano, Beatriz Matarranz, and Luis Sánchez*
Abstract: We report herein studies on the hierarchical self-assembly
vs. pathway complexity of N-annulated perylenes 1-3, that differ only
in the nature of the linking groups connecting the perylene core and
the side alkoxy chains. Despite the structural similarity, compounds 1
and 2 exhibit noticeable differences in their self-assembly. While 1
forms an off-pathway aggregate I that converts over time (or by
addition of seeds) into the thermodynamic product A, 2 undergoes a
hierarchical process in which the kinetically trapped monomer species
Herein, we investigate the self-assembly of a series of N-
annulated perylenes (compounds 1-3 in Figure 1a) in which the
number and/or the position of the amide functional groups is
modified. Dicarboxamides 1 and 2 form kinetically trapped
species by intramolecular H-bonding, termed metastable
monomers, that evolve in a different outcome (Figure 1b).
Compound 1 shows a pathway complexity in which the inactivated
monomeric species are stored as an off-pathway aggregate I that
does not lead to a kinetically controlled supramolecular growth. Finally, kinetically switch into on-pathway, helical structures A. This out-
compound 3, which lacks the amide groups, is unable to self-
assemble under identical experimental conditions and highlights the
key relevance of the amide groups and their position to govern the
self-assembly pathways.
of-equilibrium process can be accelerated by the addition of
seeds (Figure 1c). Compound 2 also forms kinetically trapped
monomers that evolve very rapidly and efficiently to form
superhelical structures (Figure 1d). The fast evolution of the
monomeric species and the high stability of the final interdigitated
supramolecular entities impede performing SSP. The lack of
amide functional groups in compound 3 results in an inefficient
self-assembly process despite the large aromatic surface of this
perylene derivative. The comparison of these characteristics to
those shown for closely related systems (compounds S1[7] and
S2[8] in Figure S1) demonstrates the strong effect of the number
and/or position of functional groups, like amides and paraphinic
side chains, to program the course of a seeded supramolecular
polymerization. The results presented in these studies allows
establishing some basic rules about the structural requirements
of a self-assembly unit necessary to experience a efficient SSP
that yields supramolecular polymers of precise size and
polydispersity, controlling the different levels of hierarchy.[9]
Supramolecular polymerization is a research area in continuous
motion to find out new functionalities for organic and
organometallic molecular entities able to self-assemble in an
organized manner by the operation of non-covalent forces.[1] To
achieve this goal, controlling size, polydispersity, and molecular
sequence is a must. In analogy to covalent polymers,[2] seeded
supramolecular polymerization (SSP) has emerged as a very
useful technique to construct complex supramolecular
structures.[3] A vast majority of supramolecular polymers, formed
through an isodesmic or
a cooperative mechanism, are
investigated under thermodynamic control.[1] There are scarce
examples of kinetically controlled supramolecular polymerization
that proceeds through the formation of metastable species that,
in addition, are crucial for the consecution of seeded
supramolecular polymerizations.[4,5] The kinetically trapped
species generate an out-of-equilibrium scenario in which the
nucleation of the monomers, prior to the subsequent elongation,
is retarded.[4] In this situation, the controlled addition of seeds or
initiators notably accelerates the formation of the supramolecular
polymers.[5,6] A number of examples of SSP demonstrate the
operation of intramolecular H-bonds to yield kinetically trapped
inactive species that do not evolve spontaneously but upon the
addition of seeds to afford the corresponding supramolecular
polymers.[5,6]
[a]
E. E. Greciano, B. Matarranz, Prof. Dr. L. Sánchez
Departamento de Química Orgánica
Facultad de Ciencias Químicas, Universidad Complutense de
Madrid
Figure 1. a) Chemical structure of the N-annulated perylenes 1-3; b) Schematic
representation of the formation of inactive monomeric species. Energy
landscapes of the supramolecular polymerization of 1 (pathway complexity and
SSP in c) and 2 (hierarchical self-assembly in d).
Ciudad Universitaria s/n; 28040-Madrid (Spain)
E-mail: lusamar@quim.ucm.es
Supporting information for this article is given via a link at the end of
the document.
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N-annulated perylenes 1-3 were synthesized from the
dibromo derivative 4 and the corresponding boronic acid (9, 12 or
13) by a Suzuki C–C cross-coupling reaction. The chemical
structure of all new reported compounds has been confirmed
using NMR, FT-IR, UV-Vis spectroscopy, and HRMS analyses
(see Scheme S1 and Supporting Information).
pattern coincides with that observed for the tetraamide S2 in
toluene as solvent.[8] On the contrary, the aggregated state of 2
exhibits a hypsochromic shift and a hypochromic effect with an
absorption maxima at  = 414 nm and a shoulder at  = 457 nm
(Figure 2b). The spectroscopic features of aggregated 2 are
identical to that observed for S1 and S2 in MCH as solvent.[7,8] To
elucidate the mechanism governing the supramolecular
polymerization of both 1 and 2, we have registered cooling curves
of these compounds at different concentrations (Figure 2c, 2d, S4
and S5). These cooling curves, are composed by two segments
intersecting in a temperature that increases with increasing the
concentration, cannot be fitted neither to an isodesmic nor to a
cooperative model.[1a] In addition, the heating curves of freshly
prepared 1 are similar in shape to that registered in the cooling
process but with different UV-Vis spectra (Figure 2c and S4).
Noteworthy, the heating curve of 2 presents two clear points in
which the mechanism changes but with identical UV-Vis spectra
at low temperatures for the heating and cooling processes (Figure
2d and S5). All these findings imply the operation of more complex
supramolecular polymerization mechanisms, other than
isodesmic or cooperative, in which a hierarchical organization of
the supramolecular structures could take place (see below).[10]
The supramolecular polymerization of 1-3 has been initially
investigated by variable temperature (VT) UV-Vis spectra in
methylcyclohexane (MCH) as solvent. Compounds 1 and 2 show
the characteristic vibronic structure of perylenes, with maxima at
398, 427, and 450 nm at high temperature (Figure 2a, 2b and S2).
This pattern coincides with that observed for the tetraester 3 at
room temperature, which implies the lack of intermolecular
interaction of this compound under these experimental conditions
(Figure S3). The UV-Vis spectra at room temperature of 1,
endowed with an inner amide group, and 2, bearing the amide
group at the outer position, experience a broadening effect and a
hypsochromic shift characteristic of an aggregation process.
Interestingly, a closer inspection in the UV-Vis spectra of 1 and 2
at low temperature shows that the spectroscopic features for the
aggregated species are different (Figure S2). In the case of 1, the
spectroscopic pattern consists in two absorption maxima at  =
432 and 457 nm and a shoulder at  = 410 nm (Figure 2a). This
Figure 2. UV-Vis spectra of 1 (a) and 2 (b) in MCH as solvent registered after cooling the sample at 1K/min; Cooling and heating curves of 1 (c) and 2 (d) obtained
upon monitoring the absorbance at 450 nm (MCH, 1K/min)
The broadening effect and the hypsochromic shift observed in
the UV-Vis spectra of 1 and 2 upon decreasing the temperature
are diagnostic of the formation of H-like aggregates from the
molecularly dissolved state (Figures 2a, 2b and S6). Similarly to
compounds S1 and S2, the -stacking of the aromatic skeletons
is visualized by the upfield shift of the resonances corresponding
to the N-annulated perylene moiety. The deshielding effect
experienced by the triplet corresponding to the amide protons
upon increasing the concentration implies the intermolecular H-
bonding interaction between the amides (Figure 3).[11]
Interestingly, the singlet ascribable to the protons of the
trialkoxyphenyl rings experiences no shift for 1 but shifts downfield
in 2, which indicates a slightly different packing of these two N-
annulated perylenes (Figure 3).
comparison to 2. In addition, the presence in both 1 and 2 of a
shoulder at   480 nm implies a rotational displacement of the
molecules in the stack.[12] Considering that the distance from the
amide group to the core and the flexibility of the spacers are the
main differences between the two molecules, this should have an
important effect to determine the molecular packing in both cases.
In both N-annulated perylenes, the formation of a double H-
bonding array is essential to maintain the longitudinal order.[7b]
The presence of the amide and ester groups in 1 and 2 should
allow the intramolecular N-H···O=C H-bonding interaction to form
a seven-membered pseudocycle that affords kinetically trapped
monomeric species.[5b,5c,5d,8] We have demonstrated that both 1
and 2 afford this inactive monomeric form by using different
spectroscopic techniques. The spectroscopic pattern of 2 mM
solutions of 1 and 2 in CDCl3 coincides with that observed for the
molecularly dissolved state (Figure S7). VT-1H NMR spectra
shows the shielding effect experienced by the triplet
corresponding to the protons of the amide group upon increasing
Taking into account all the above spectroscopic evidences, it
is possible to shed some light on the aggregation mode of both 1
and 2. Thus, the lower wavelength observed in the UV-Vis
spectrum of aggregated 1 implies a more ideal H-type packing in
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the temperature. However, all the aromatic and aliphatic
resonances experience no shift (Figure S8). The upfield shift of
the amide protons at high temperatures is indicative of the rupture
of the intramolecular H-bonds in the pseudocycle. The formation
of the inactivated monomers has been confirmed by 2D-ROESY
experiments in which both 1 and 2 show through space contacts
between the amide protons and the aromatic protons of the
external 3,4,5-trialkoxybenzamide moiety (Figure S9). The
additional through-space contacts between the ortho proton of the
benzamide unit with the trialkoxy ring and also with the methylene
joint to the oxygen in this same unit corroborates this structure
(Figure S9).
Consequently, we have investigated the time course of the
inactivated monomers of 1 and 2. The heating-cooling cycles
performed for 1 show the formation of different aggregates in both
cycles (Figure S2), indicative of the storing of the inactivated
monomeric form into an initial intermediate aggregate (I in Figure
1c) that evolves spontaneously to a different aggregated state (A
in Figure 1c). The kinetic profile of a 300 M solution of 1 in MCH
heated at 85 ºC and rapidly cooled shows a sigmoidal shape
characteristic of an autocatalytic process that yields the
supramolecular polymerization of 1 after a lag time (Figure 4a).
This lag time decreases upon decreasing the temperature (Figure
4a) but increases upon increasing the concentration (Figure 4b).
The influence of temperature and concentration on the kinetics
confirms the initial formation of off-pathways aggregate I that
In the examples reported so far, the formation of kinetically
trapped monomers guarantees the performance of SSP.[5b,5c,5d,8]
evolves to the on-pathway aggregate
A (Figure 1c and
S10).[5a,5d,6a,8] The addition of seeds, prepared by the sonication
of a freshly prepared solution of 1 in MCH at cT = 300 M for 5
min, accelerates the kinetics of the transformation of the off-
pathway aggregate into the on-pathway supramolecular structure
(Figure 4c). The ratio between the off-pathway aggregate and the
on-pathway seeds plays a determinant role in the acceleration of
the transformation between these two states and only at relatively
high percentage of seeds it is possible to speed up the conversion.
The situation is completely different in compound 2. This
dicarboxamide form kinetically trapped species and exhibits a
complex supramolecular polymerization mechanism. The UV-Vis
spectra obtained for 2 in aggregated state experience a severe
broadening effect in comparison to the molecularly dissolved
species, with practically no differences between the spectra
registered for the aggregates of a freshly prepared solution at 20
ºC (Figure S2). In fact, monitoring the kinetic evolution of the
conversion of these aggregated species at 30 ºC results in an
exponential decay with no lag time (Figure S11).[13] At lower
temperature, the UV-Vis spectrum of the aggregate of
2
undergoes no changes. To the best of our knowledge, this is the
first example of a system in which the formation of kinetically
trapped monomeric species do not afford kinetically controlled
supramolecular processes and, consequently, it is not possible to
perform SSP.
Figure 3. a Concentration-dependent 1H NMR spectra of 1 (a) and 2 (b) in
CDCl3 (300 MHz, 298 K) showing the aromatic, the amide and the methylene
linked to the nitrogen and oxygen atom protons.
Figure 4. Kinetic profiles of the evolution of the off-pathway aggregate I of compound 1 at different temperatures at cT = 300 M (a), different concentrations at 10
ºC (b); and after the addition of seeds at different ratios (cT = 300 M; T = 15 ºC) (c).
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Atomic force microscopy (AFM) imaging contributes to clarify
the differences found in the supramolecular polymerization of 1
and 2 and to stablish structural rules to control the consecution of
SSP. AFM images of 1 show the formation of bundles of short,
helical fibers of 4.5 Å demonstrating the low trend of the fibrillary
structures of 1 to pack (Figure 5a, 5b and S12). The AFM images
of 2 show a dense network of superhelical structures that strongly
bundle into thick filaments of several micrometers length and
minimal heights of 12 Å (Figure 5c, 5d and S13). The AFM images
of 2 demonstrate the strong tendency of this unit to undergo a
preferred hierarchical self-assembly that rapidly shifts all the
equilibria involved in its aggregation. The high stability of the final
aggregates results in a rapid shift along the energy landscape
from the monomers to the superhelical aggregates (Figure 1d).
However, in 2, the formation of the H-bonds between the outer
amides cancels the conformational freedom of the peripheral
units that favors, firstly, a efficient -stacking of the central
perylene moiety and, in addition, the disposition of the external
paraphinic chains to interdigitate. The dissimilar packing of the
self-assembling units and the further intertwining of the external
chains produce a hierarchical process that finally generates
superhelical structures.[14] The results presented herein validate
that a fine-tuned molecular design determines the out-of-
equilibrium outcome during the supramolecular polymerization
and allow stablishing some basic rules about the structural
requirements of a self-assembly unit necessary to experience a
efficient SSP that yields supramolecular polymers of controlled
size and polydispersity tuning the different hierarchical levels of
organization.
Acknowledgements
Financial support by the MINECO of Spain (CTQ2014-53046-P,
CTQ2017-82706-P)
and
the Comunidad de Madrid
(NanoBIOSOMA, S2013/MIT-2807) is acknowledged. E. E. G. is
grateful to Universidad Complutense de Madrid for a predoctoral
grant.
Keywords: hierarchy • out-of-equilibrium • pathway complexity •
seeded self-assembly • supramolecular polymers
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Table of Contents
COMMUNICATION
E. E. Greciano, B. Matarranz, L.
Sánchez*
Page No. – Page No.
Pathway complexity versus
hierarchical self-assembly in N-
annulated perylenes. Structural
effects in seeded supramolecular
polymerization
The number and position of amide functional groups exerts a determinant role in
the self-assembly outcome of N-annulated perylenes. The inner amides favour an
out-of-equilibrium system in which the pathway complexity can be accelerated by
seeding. The outer amides generate more planar molecular systems that
experience a rapid hierarchical self-assembly to produce superhelical structures.
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