H-aggregates of oligophenyleneethynylene (OPE)-BODIPY systems in water: Guest size-dependent encapsulation mechanism and co-aggregate morphology

Article abstract of DOI:10.1002/chem.201402077

The synthesis of a new oligophenyleneethynylene (OPE)-4,4-difluoro-4-bora- 3a,4a-diaza-s-indacene (BODIPY) bolaamphiphile 1 and its aqueous self-assembly are reported. Compound 1 forms H-type aggregates in aqueous and polar media, as demonstrated by UV/Vis and fluorescence experiments. Concentration-dependent ¹H NMR studies in CD₃CN reveal that the BODIPY units are arranged on top of each other into π-stacks with H-type excitonic coupling, as supported by ROESY NMR and theoretical calculations and visualized by Cryo-SEM studies. A detailed analysis of the spectral changes observed in temperature-dependent UV/Vis studies reveals that 1 self-assembles in a non-cooperative (isodesmic) fashion in water. The hydrophobic interior of these self-assembled structures can be exploited to encapsulate hydrophobic dyes, such as tetracene and anthracene. Both dyes absorb in a complementary region of the UV/Vis spectrum and are small enough to interact with the hydrophobic segments of 1. Temperature-dependent UV/Vis studies reveal that the spectral changes associated to the encapsulation mechanism of tetracene can be fitted to a Boltzmann function, and the initially flexible fibres of 1 rigidify upon guest addition. In contrast, the co-assembly of 1 and anthracene is a highly cooperative process, which suggests that a different class of (more-ordered) aggregates is formed. TEM and Cryo SEM imaging show the formation of uniform spherical nanoparticles, indicating that a subtle change in the guest molecular structure induces a significant change in the encapsulation mechanism and, consequently, the aggregate morphology. Dye encapsulation: We report the aqueous self-assembly of a new oligophenyleneethynylene (OPE)-BODIPY amphiphilic derivative into H-type aggregates and its ability to encapsulate hydrophobic guest molecules. Subtle changes in the guest size induce a dramatic change of the encapsulation mechanism. Addition of tetracene leads to the non-cooperative formation of stiff fibres, whereas co-assembly with anthracene is a highly cooperative process, leading to highly organized micellar assemblies.

Full text of DOI:10.1002/chem.201402077

DOI: 10.1002/chem.201402077
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&
Supramolecular Chemistry
H-Aggregates of Oligophenyleneethynylene (OPE)-BODIPY
Systems in Water: Guest Size-Dependent Encapsulation
Mechanism and Co-aggregate Morphology**
Naveen Kumar Allampally, Alexander Florian, Marꢀa Josꢁ Mayoral, Christina Rest,
Vladimir Stepanenko, and Gustavo Fernꢂndez*[a]
Dedicated to Professor Frank Wꢀrthner on the occasion of his 50th birthday.
Abstract: The synthesis of a new oligophenyleneethynylene
(OPE)-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)
Both dyes absorb in a complementary region of the UV/Vis
spectrum and are small enough to interact with the hydro-
phobic segments of 1. Temperature-dependent UV/Vis stud-
ies reveal that the spectral changes associated to the encap-
sulation mechanism of tetracene can be fitted to a Boltz-
mann function, and the initially flexible fibres of 1 rigidify
upon guest addition. In contrast, the co-assembly of 1 and
anthracene is a highly cooperative process, which suggests
bolaamphiphile 1 and its aqueous self-assembly are report-
ed. Compound 1 forms H-type aggregates in aqueous and
polar media, as demonstrated by UV/Vis and fluorescence
experiments. Concentration-dependent 1H NMR studies in
CD3CN reveal that the BODIPY units are arranged on top of
each other into p-stacks with H-type excitonic coupling, as
supported by ROESY NMR and theoretical calculations and
visualized by Cryo-SEM studies. A detailed analysis of the
spectral changes observed in temperature-dependent UV/Vis
studies reveals that 1 self-assembles in a non-cooperative
(isodesmic) fashion in water. The hydrophobic interior of
these self-assembled structures can be exploited to encapsu-
late hydrophobic dyes, such as tetracene and anthracene.
that
a different class of (more-ordered) aggregates is
formed. TEM and Cryo SEM imaging show the formation of
uniform spherical nanoparticles, indicating that a subtle
change in the guest molecular structure induces a significant
change in the encapsulation mechanism and, consequently,
the aggregate morphology.
phiphilic p-systems[12] in a large number of natural supramolec-
ular assemblies.[13] In particular, the understanding of the ther-
modynamic aspects and mechanisms by which these nano-ob-
jects self-assemble in aqueous medium or encapsulate and re-
lease guest molecules is of high relevance to the field of bio-
medicine.
Introduction
The exceptional optical and electronic properties of 4,4-di-
fluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) dyes[1] have fa-
cilitated their implementation as fluorescent indicators,[2] laser
dyes,[3] biolabeling[4] and photodynamic therapy agents[5] or
active materials for optoelectronics[6] in recent years. For most
of these applications, the investigation of the self-assembly
pathways and bulk-state organization of the dye molecules is
a prerequisite.[7] BODIPY derivatives are known to self-assemble
through stacking of their dipyrromethene core,[8] which has
been exploited to construct dye aggregates primarily in organ-
ic solvents[9] and in the bulk or liquid crystal state.[10] In con-
trast, extended aggregates of amphiphilic BODIPY dyes in
water[11] remain unexplored, despite the great relevance of am-
To date, different forms of soft matter, in particular supra-
molecular gels,[14] have been used for the encapsulation of
guest molecules for sensing applications, drug delivery, cataly-
sis, or crystal growth. Encapsulation of guests by these assem-
blies can also produce new nanostructured architectures with
innovative properties.[15] A particularly exciting approach is the
utilization of nanofiber solutions and hydrogels as artificial 3D
cell culture supports that mimic the natural extracellular
medium,[16] which can even maintain mammalian cells in 3D
environments for tissue regeneration applications.[17] The inter-
face of artificial self-assembled structures with biological sys-
tems would certainly benefit from a better comprehension of
the mechanisms taking place during binding, which might be
exploited to control the morphology of the resulting co-aggre-
gate structures.
[a] Dr. N. K. Allampally, A. Florian, Dr. M. J. Mayoral, C. Rest, Dr. V. Stepanenko,
Dr. G. Fernꢁndez
Institut fꢀr Organische Chemie and Center for Nanosystems Chemistry
Universitꢂt Wꢀrzburg Am Hubland, 97074 Wꢀrzburg (Germany)
Fax: (+49)931-31-84756
E-mail: gustavo.fernandez@uni-wuerzburg.de
In our group, we have recently reported the synthesis and
self-assembly of a nonpolar oligophenyleneethynylene (OPE)-
BODIPY derivative substituted with peripheral dodecyl chains
[**] BODIPY=4,4-difluoro-4-bora-3a,4a-diaza-s-indacene.
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201402077.
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Scheme 1. Synthesis of the target BODIPY-OPE amphiphile 1.
(Scheme 1, top). Our p-conjugated system self-assembles in
nonpolar media such as cyclohexane into needle-like associ-
ates primarily driven by p–p interactions involving the BODIPY
and OPE fragments.[9a] The high solubility of the nonpolar OPE-
BODIPY in cyclohexane (ꢀ30 mm) and, consequently, the ab-
sence of strong solvophobic interactions induces a moderate
value of binding constant (Ka ꢀ1ꢄ104 mꢁ1) in this solvent. This
phenomenon appears to be responsible for the formation of
one-dimensional associates in which the OPE and BODIPY frag-
ments are forming slipped stacks leading to a zigzag-like ar-
rangement within the fibres. An obvious next step would be
to scrutinize whether this intriguing organization is influenced
in water, a unique medium in which strong hydrophobic inter-
actions are the chief driving force to create self-assembled
structures. As a result of that, the expected self-assembled
structures would feature confined areas that provide an ideal
environment for hydrophobic or aromatic guest molecules
to be encapsulated and released under certain external
conditions.
Figure 1. a) UV/Vis (1ꢄ10ꢁ5 m, 298 K) and b) emission spectra of
1 (1ꢄ10ꢁ5 m and 2 mm, 298 K) in different solvents. For (a), all concentra-
tions are 1ꢄ10ꢁ5 m.
ꢀ410 nm (S0!S2 transition); Figure 1a and Table 1). No signifi-
cant spectral changes are observed upon solvent variation
with the exception of polar acetonitrile and water (Figure 1a,
Table 1 and Figure S1 in the Supporting Information). For both
solvents, the S0!S1 transition corresponding to the BODIPY
core is broadened and blue-shifted. This trend is much more
pronounced in water, in which a red-shifted shoulder at about
600 nm is also noticeable (Figure 1a). The hypsochromic shift
of the absorption maximum in water along with the appear-
ance of a shoulder at 590 nm indicates a side-on arrangement
of the molecules into H-aggregates with partial allowance of
the lower energy transition due to a twisted dye conformation
within the stack.[21] Simultaneously, the transition at approxi-
Herein, we describe the aqueous self-assembly of a new am-
phiphilic oligophenyleneethynylene (OPE)-BODIPY derivative
(1) into flexible fibre-like H-aggregates and their reversible
transformation into rigid fibres or spherical nanoparticles upon
addition of tetracene and anthracene, respectively, which is ac-
companied by a change in the encapsulation mechanism from
isodesmic to cooperative.
Results and Discussion
Amphiphile 1 (Scheme 1) has been synthesized by
Table 1. Optical properties of 1 in different solvents (1ꢄ10ꢁ5 m, 298 K).
a
Sonogashira cross-coupling reaction[18] of 2,6-
[c]
Solvent
ENT 24
labs
[nm] [nm]
OPE
S0!S1
labs
e
lem
Stokes
FF
diiodo-BODIPY (2)[19] and triethyleneglycol (TEG)-sub-
stituted OPE derivative 3[20] (see Supporting Informa-
[mꢁ1 cmꢁ1
]
[nm][a] shift[b] [nm]
1
tion) in 57% yield and fully characterized by H and
13C NMR, MALDI-TOF, high resolution ESI, UV/Vis and
fluorescence spectroscopy (see Supporting Informa-
tion).
CHCl3
0.259 340
0.309 340
0.164 340
0.207 339
0.775 336
0.460 331
1.000 338
573
570
568
567
563
555
534
65730, 85800 612
68458, 88300 603
71053, 92500 610
72051, 89100 604
76669, 90000 600
65592, 70658 598
60610, 39200 647
39
33
42
37
37
43
113
0.74
0.72
0.71
0.70
0.62
0.48
0.01
CH2Cl2
1,4-Dioxane
THF
MeOH
CH3CN
H2O
The optical properties of 1 have been analysed by
UV/Vis and fluorescence spectroscopy in different sol-
vents. The UV/Vis spectra show the characteristic ab-
sorption bands of both OPE (ꢀ330–340 nm) and
BODIPY fragments (ꢀ570 nm (S0!S1 transition) and
[a] lex =labs. [b] labs(S0!S1)–lem. [c] A<0.05;[25] estimated error: ꢂ2%.
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CD3CN. The broadening of most
of the resonances is concomitant
with the upfield shift of the aro-
matic signals upon increasing
concentration (Figure 2a). The
fact that the signals correspond-
ing to the BODIPY core undergo
the largest upfield shifts whereas
the polar triethyleneglycol (TEG)
chains are barely sensitive to
concentration suggests the for-
mation of H-type p-stacks with
a slight rotation angle between
the BODIPY units (see models in
Figure 3 and Figure S3 in the
Supporting Information). This hy-
pothesis is supported by the
presence of coupling signals be-
tween the aromatic protons (Hd)
of the phenylene rings belong-
ing to the OPE fragments and
the methyl groups (Hb and Hc) of
the BODIPY as well as between
aromatic protons Hd and He in
the rotating-frame Overhauser
effect spectroscopy (ROESY) ex-
periments of 1 in CD3CN (Fig-
ure 2b and c, and Figures S4
and S5 in the Supporting Infor-
mation). Such arrangement is
considerably more favourable
than the formation of slipped
stacks, as strong solvophobic
and p–p forces will be maxi-
mized if the dyes are arranged in
a parallel fashion. Transmission
Scheme 2. Cartoon representation of the self-assembly of 1 into H-type aggregates and its reversible guest-de-
pendent encapsulation processes.
mately 330–340 nm becomes sharper in water and acetonitrile,
which is indicative of the planarization of the alkyne-aryl
groups of the OPE fragments and represents a measure of the
propensity of the p-system to self-assemble.[22] With regards to
the emission properties, the spectra of 1 in acetonitrile and
water are red-shifted and remarkably quenched compared to
those in chloroform, dichloromethane or methanol (Figure 1b
and Table 1). These findings suggest the formation of p-stacks
with H-type excitonic coupling[23] between the BODIPY frag-
ments (Scheme 2).
The self-assembly of 1 in solution was initially investigated
1
through 1D and 2D NMR spectroscopy. The H NMR spectrum
of 1 in D2O shows broad signals even at high temperature
(353 K) and dilution (0.5 mm) as a result of a high degree of
1
aggregation of 1 in aqueous medium. In contrast, the H NMR
signals in [D3]acetonitrile are well-resolved and sensitive to
1
Figure 2. a) Partial H NMR spectra of 1 at different concentrations (CD3CN,
400 MHz, 298 K). Details of ROESY NMR spectrum of 1 (CD3CN, 600 MHz,
4 mm, 298 K) showing the coupling signals of methyl groups Hb and Hc with
aromatic protons Hd (b) and between aromatic protons Hd and He (c).
concentration changes (Figure S2 in the Supporting Informa-
tion). Figure 2a shows the concentration-dependent 1H NMR
experiments (400 MHz, 298 K) of 1 between 0.08 and 10 mm in
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Figure 3. Force field optimized-geometry of seven molecules of amphiphilic
OPE-BODIPY derivative 1, a) side and b) top views and for two molecules c)
side and d) top views (Macromodel).
electron microscopy (TEM) studies on a carbon-coated copper
grid show the appearance of a network composed of elongat-
ed supramolecular objects with lengths up to about 300 nm,
which is in agreement with NMR experiments (Figure S6 in the
Supporting Information).
Figure 4. a) Temperature-dependent UV/Vis studies of 1 in water (3ꢄ10ꢁ5 m).
Arrows indicate spectral changes upon temperature decrease. Inset: Fitting
of the fraction of aggregated species (aagg) against T at 520 nm to the iso-
desmic model. b) Cryo-SEM image of 1 prepared from water solution
(5ꢄ10ꢁ5 m, 123 K).
The self-assembly of 1 in water has been analysed in detail
by temperature-dependent UV/Vis experiments, as this
method covers the concentration range in which the transition
from monomeric to H-aggregated species of 1 takes place. The
spectral changes have been monitored by cooling down aque-
ous solutions of 1 at four different concentrations (1–4ꢄ
10ꢁ5 m) at a rate of 0.5 Kminꢁ1. Above 343 K, the TEG chains
are dehydrated as a consequence of the lower critical solution
temperature (LCST) in water and less soluble species are
formed.[26] However, the monomer-to-aggregate transition of
1 in water can be fully tracked if the solutions are slowly
cooled down from 338 to 275 K (Figure 4a and Figures S7 and
S8 in the Supporting Information). With decreasing tempera-
tures, the sharpening of the OPE transition at 338 nm is ac-
companied by the hypsochromic shift of the S0!S1 transition
corresponding to the BODIPY unit from 549 to 539 nm (Fig-
ure 4a). Additionally, the shoulder at 590 nm is absent at high
temperature and becomes progressively more pronounced as
the temperature decreases, indicating the excitonic coupling
of the BODIPY units in a twisted H-type fashion. The appear-
ance of isosbestic points at approximately 300 and 550 nm is
indicative of equilibrium between monomeric and aggregated
species. The thermodynamic parameters associated to the self-
assembly process of 1 in water (see Table 2) have been deter-
mined by fitting the molar absorptivity (e) against temperature
at 520 nm to the isodesmic model.[27] According to this model,
all binding events are isoenergetic. At room temperature, bind-
ing constants (Ka) ranging from of 0.9 to 1.5ꢄ106 mꢁ1 and
a melting temperature (Tm) of about 314–317 K have been cal-
culated (Table 2).
Table 2. Thermodynamic parameters Ka, Tm, DH8, DG8 and DS8 obtained
from the temperature-dependent UV/Vis experiments of BODIPY in water
at different concentrations (298 K, l=520 nm).
Conc.
[m]
Ka
[mꢁ1
Tm
[K]
DPN DH
[kJmolꢁ1
DS
DG
[kJmolꢁ1
]
]
]
[Jmolꢁ1 Kꢁ1
]
1ꢄ10ꢁ5 1.0ꢄ106 314.4 1.41 ꢁ155.2
2ꢄ10ꢁ5 1.3ꢄ106 314.9 1.42 ꢁ192.8
3ꢄ10ꢁ5 0.9ꢄ106 315.4 1.42 ꢁ197.5
4ꢄ10ꢁ5 1.5ꢄ106 316.7 1.42 ꢁ182.0
ꢁ405.8
ꢁ530.1
ꢁ548.6
ꢁ492.6
ꢁ34.25
ꢁ34.80
ꢁ34.02
ꢁ35.17
The aggregate size in solution has been determined by dy-
namic light scattering (DLS). In accordance with previous NMR
and UV/Vis experiments, DLS studies demonstrate that 1 forms
self-assembled structures in both acetonitrile and water at
a concentration of 2 mm, with the average particle sizes being
considerably larger in the latter (ꢀ250 nm for acetonitrile and
ꢀ1100 nm for water) as a result of increased hydrophobic in-
teractions (Figure 5 and Figure S9 in the Supporting Informa-
tion). For both solvents, the fact that the size distribution is de-
pendent on the scattering angle strongly suggests the forma-
tion of anisotropic one-dimensional aggregates.[15a,28]
The morphology of the aggregates formed by 1 at a concen-
tration of 5ꢄ10ꢁ5 m in water has been examined by cryogenic
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Figure S3 in the Supporting Information). This organization is
in good agreement with the optical signatures of the H-aggre-
gates with a twisted arrangement of the chromophores within
the stack.
The hydrophobic interior of the fibrillar assemblies formed
by amphiphile 1 in water can be ultimately exploited to encap-
sulate aromatic guest molecules. As hydrophobic guest, we ini-
tially chose a polycyclic aromatic hydrocarbon (tetracene) due
to its appropriate small size and absorption in the UV/Vis
region, which is complementary to the spectral features of am-
phiphile 1. When one or two equivalents of tetracene are
added to an aggregate solution of 1 at a concentration of 3ꢄ
10ꢁ5 m in water, an immediate solubilisation of the hydropho-
bic dye is observed, indicating that an effective uptake of the
guest molecules by the fibrillar assemblies takes place. The
equimolar solution remains clear for several weeks without any
sign of precipitation, suggesting the formation of stable co-as-
semblies. However, the addition of a higher amount of tetra-
cene (above 1.5–2 equivalents) results in the formation of pre-
cipitates, clearly indicating that the excess molecules of tetra-
cene can no longer be entrapped by the fibrillar assemblies of
1. The encapsulation process has been monitored by UV/Vis
experiments. After addition of one equivalent of tetracene to
the aqueous solution of 1, only slight spectral changes are ob-
served (Figure 6a).
Figure 5. Size distribution from CONTIN analysis of the autocorrelation func-
tion of 1 a) in acetonitrile and b) in water (2 mm, 298 K) from DLS
experiments.
scanning electron microscopy (Cryo-SEM) at 123 K. The images
show the appearance of flexible fibrillar associates with diame-
ters ranging from approximately 7 to 40 nm and lengths of
several microns (Figure 4b and Figure S10 in the Supporting
Information). The thinnest aggregates (6–7 nm) possess
a single-molecule width and grow into thicker bundles of
fibres facilitated by lateral interactions between the peripheral
TEG chains. No significant changes in the morphology of the
associates or gelation are observed up to approximately 1–
2 mm, whereas above this point the aggregates formed precip-
itate out of solution.
To shed some light on the arrangement of the monomeric
units of 1 within the fibrillar associates, we performed force
field calculations (Macro Model, Amber). The energy-optimized
structure of a set of seven monomeric units shows the forma-
tion of extended H-type aggregates in which the BODIPY units
are stacked on top of each other with a small rotation angle
(Figure 3 and Figure S3 in the Supporting Information). In this
arrangement, the F–B–F fragments of the BODIPY chromo-
phores are consecutively oriented to opposite sides to prevent
steric repulsions, in accordance with previous studies.[8] The
centre-to-centre distance between two adjacent molecules in
the stack is 3.5 ꢅ, and the slip angles that result from the rota-
tional (a) and translational (q) offset of two parallel-arranged
molecules are 208 and 608, respectively (Figure 3c and d and
Figure 6. a) Temperature-dependent UV/Vis studies of 1 in aqueous solution
(3ꢄ10ꢁ5 m) containing one equivalent of tetracene. Arrows indicate spectral
changes upon temperature decrease. Dash-dotted line: UV/Vis spectra of
tetracene in THF. Inset: Fitting of the spectral changes at 510 nm to the iso-
desmic model. b) SEM and c) cryo-SEM images of 1 mixed with one equiva-
lent of tetracene (water, 1ꢄ10ꢁ5 m).
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Upon closer inspection, we noticed the appearance of new
maxima of relatively low intensity at approximately 480, 510
and 530 nm that are to some extent hidden below the S0!S1
transition of the BODIPY fragments of 1 (Figure 6a). These new
maxima correspond to the absorption of the tetracene units
(Figure 6a and Figures S11 and S12 in the Supporting Informa-
tion) and are remarkably red-shifted (ꢀ20–50 nm) compared
to those of the parent guest molecules in tetrahydrofuran
(dash-dotted spectrum in Figure 6a), which accounts for
a strong interaction between the molecules of 1 and tetracene.
This has been demonstrated by analysing the aggregation be-
haviour of tetracene in isolation in THF/water mixtures at 1ꢄ
10ꢁ5 m. The original absorption spectrum of tetracene in THF
remains unchanged up to a maximum amount of 70% water
(Figure S13 in the Supporting Information). Above this point,
a significant drop in intensity and red-shift of the absorption
spectra can be observed, which can be assigned to aggregate
formation at high water content driven by hydrophobic inter-
actions (Figure S13 in the Supporting Information). However,
precipitation occurs only some minutes after water addition
for all mixtures containing more than 20% of water, indicating
that tetracene molecules are by themselves not stable in aque-
ous mixtures. Interestingly, the absorption maxima of tetracene
in isolation in its aggregated state before precipitation closely
match those observed in the mixtures with amphiphile 1 in
pure water. To analyse this, we have subtracted the spectrum
of 1 from the equimolar mixture of 1 and tetracene in water
(inset of Figure S13 in the Supporting Information). The result-
ing maxima in the region between 400 and 550 nm approxi-
mately match those of tetracene in an aggregated form, thus
demonstrating that tetracene exists in an aggregated state
upon encapsulation.
278 K at 0.5 Kminꢁ1, the maxima at 550 and 336 nm sharpen
whereas the diagnostic bands of tetracene become more evi-
dent (Figure 6a and Figures S15 and S16 in the Supporting In-
formation). The appearance of an isosbestic point at about
317 nm suggests equilibrium between well-defined species.
The encapsulation mechanism has been followed by monitor-
ing the spectral changes at a given wavelength (510 nm) with
temperature. By following this procedure at four different con-
centrations (see above), cooling curves with a clear sigmoidal
shape were obtained, which can be accurately fitted to a Boltz-
mann function (inset of Figure 6a and Figure S16 in the Sup-
porting Information) and support the existence of a reversible
isodesmic co-assembly process.[29] Application of this model to
the temperature-dependent absorption changes affords bind-
ing constants (Ka) ranging from 4.7ꢄ104 mꢁ1 to 1.7ꢄ105 mꢁ1. All
thermodynamic parameters associated to this co-assembly pro-
cess are shown in Table 3. With these overall data in hand, we
Table 3. Thermodynamic parameters associated to the self-assembly pro-
cess of 1 and one equivalent of tetracene (water, 298 K, l=510 nm).
Conc.
[m]
Ka
[mꢁ1
Tm
[K]
DPN
DH
[kJmolꢁ1
DS
[Jmolꢁ1
DG
[kJmolꢁ1
]
]
]
]
2ꢄ10ꢁ5
3ꢄ10ꢁ5
4ꢄ10ꢁ5
5ꢄ10ꢁ5
1.7ꢄ105
5.6ꢄ104
6.0ꢄ104
4.7 x104
304.4
306.5
308.6
309.2
1.41
1.42
1.41
1.42
ꢁ115.7
ꢁ94.4
ꢁ102.1
ꢁ98.3
ꢁ288.8
ꢁ225.6
ꢁ251.5
ꢁ240.2
ꢁ29.8
ꢁ27.1
ꢁ27.7
ꢁ26.7
can extract two important conclusions: 1) The stability of the
co-assemblies of 1 and tetracene is considerably lower than
the fibres of 1 in isolation, as the latter binding constant is 10-
fold higher than that associated to its mixture with tetracene.
Most likely, the intercalation of tetracene units within the H-ag-
gregates formed by 1 decreases the degree of packing of the
molecules of 1 in the structure, thereby reducing the value of
binding constant of the system. 2) The binding constant of the
1:1 complex formed by 1 and tetracene determined by titra-
tion experiments (8ꢄ105 m) is higher than that associated to
the co-assembly (4.7ꢄ104–1.7ꢄ105 m) extracted from tempera-
ture-dependent UV/Vis studies. This implies that the monomer-
ic units of 1 have a higher propensity to interact with the en-
capsulated tetracene guest molecules rather than with them-
selves within the co-assembled structures. Therefore, it is ex-
pected that a temperature increase would induce the disas-
sembly of the co-assembled structures and the release of the
1:1 1/tetracene complexes as small fragments. This assumption
is supported by the fact that even at high temperature (338 K)
the water-insoluble tetracene molecules do not precipitate out
of solution, indicating that they should be in some way shield-
ed by the monomeric units of 1.
We also observed a simultaneous drop in absorption of the
BODIPY transition and a remarkable scattering in the region
above 650 nm as a result of precipitation effects when more
than 1 equivalent of tetracene was added to the aqueous solu-
tion of 1 (Figure S11 in the Supporting Information). This phe-
nomenon strongly suggests a 1:1 binding stoichiometry be-
tween the aggregates of 1 and tetracene, which is also sup-
ported by titration experiments in water/THF (99.9:0.1) mix-
tures. To perform these studies, we have prepared a concentrat-
ed (ꢀ3 mm) solution of tetracene in THF and added it to
a 300-fold more diluted solution of 1 in water, so the total
amount of THF during the titration process is almost negligible
(0.1%). Upon guest addition, the maxima at 330 and 550 nm
decrease in intensity up to around 0.8–1.1 equivalents of
guest, suggesting that the maximum amount of bound dye
molecules is one equivalent. Unfortunately, Job plot analysis
didn’t result in a clear maximum and the exact stoichiometry
cannot be determined by this method. However, the variation
in absorption at 536 nm upon tetracene addition can be fitted
to a 1:1 binding isotherm (Figure S14 in the Supporting Infor-
mation) yielding a binding constant value of 8ꢄ105 m.
The changes in the morphology of the fibrillar associates of
1 upon addition of tetracene have been investigated by SEM
and cryo-SEM studies and are depicted in Figure 6b and c. The
SEM images of an equimolar mixture of 1 and tetracene show
that the initially flexible fibres of 1 dramatically stiffen upon
addition of tetracene, whereas their length (several microns)
The reversibility of the encapsulation process has been ana-
lysed in detail by temperature-dependent UV/Vis experiments
at concentrations between 2 and 5ꢄ10ꢁ5 m. On cooling down
an equimolar mixture of 1 and tetracene in water from 338 to
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and width (40–500 nm) become larger than those of the pris-
tine fibres of 1 (Figure 6b and Figure S17 in the Supporting In-
formation), as a result of stronger hydrophobic interactions.
The aromatic tetracene units are most likely randomly packed
within the hydrophobic domain of the fibres, leading to an in-
creased rigidity of the system, as shown in Scheme 2, top.
Cryo-SEM images of this mixture reveals that the stiff associ-
ates of 1 and tetracene are in turn composed of thinner fila-
ments that grow laterally into bundles through interactions be-
tween the TEG chains (Figure 6c and Figure S18 in the Sup-
porting Information). DLS studies demonstrate that the aver-
age aggregate size of the mixed assembly (ꢀ1300 nm) is com-
parable to that of 1 in isolation (ꢀ1100 nm, Figure S19 in the
Supporting Information), which is in full agreement with UV/
Vis and SEM investigations.
We next questioned whether the encapsulation mechanism
and morphology of the aggregates formed upon guest addi-
tion would be dependent on the size of the hydrophobic
guest molecule. However, In the course of the encapsulation
experiments of tetracene, we found out that the spectral fea-
tures of tetracene overlap with those of the BODIPY fragments
of 1, making the process rather difficult to follow. To overcome
this issue, we envisaged that a slightly shorter hydrophobic
polycyclic aromatic hydrocarbon, anthracene, would be
a better match to our BODIPY-OPE amphiphile 1, both from
a geometrical and electronic point of view. Similarly to tetra-
cene, the addition of up to two equivalents of anthracene to
an aqueous aggregate solution of 1 results in the solubilisation
of the dye molecules by the aqueous aggregates of 1, indicat-
ing an effective encapsulation of anthracene as well. Titration
experiments in water containing traces of THF (0.1%) show the
reduction of the BODIPY and OPE maxima upon addition of an-
thracene and the appearance of two isosbestic points at 300
and 506 nm (Figure S20 in the Supporting Information). Job
plot analysis reveals a 1:1 stoichiometry between 1 and anthra-
cene (Figures S21 and 22 in the Supporting Information). The
spectral changes observed during the titration studies at
536 nm can be fitted to a 1:1 binding isotherm (Figure S20 in
the Supporting Information) yielding a value of binding con-
stant (8ꢄ105 m) that is very similar to that associated to tetra-
cene binding.
Figure 7. a) Temperature-dependent UV/Vis studies of 1 in aqueous solution
(2ꢄ10ꢁ5 m) containing one equivalent of anthracene. Arrows indicate spec-
tral changes upon temperature decrease. Dash-dotted line: UV/Vis spectra
of anthracene in THF. Inset: Fitting of the spectral changes at 555 nm to the
ten Eikelder–Markvoort–Meijer model. b) and c) TEM images of 1 and one
equivalent of anthracene on carbon-coated copper grid (water, 1ꢄ10ꢁ5 m).
mation). Additionally, the absorption maxima of anthracene
upon encapsulation closely match those of anthracene alone
in an aggregated state in THF/water mixtures when the water
content exceeds 90%, again demonstrating that anthracene
exists in a self-assembled state in the mixture with 1 (Fig-
ure S23 in the Supporting Information). Nevertheless, due to
the low solubility of anthracene in aqueous mixtures, precipita-
tion occurs only some minutes after water addition.
On the other hand, heating the 1:1 mixture of 1 and anthra-
cene solution up to 338 K, leads to more significant changes in
the absorption spectra compared to low temperature (see red
spectrum in Figure 7a). For instance, the diagnostic transition
of anthracene at 250 nm dramatically increases upon increas-
ing temperature, which indicates that at high temperatures
the anthracene units are released from the supramolecular ag-
gregates of 1 (Figure 7a). The fact that the original spectrum
(see blue line in Figure 7a) is recovered upon cooling down
the solution back to 278 K along with the appearance of an
isosbestic point at 268 nm indicates a reversible equilibrium
between free and encapsulated guest species.
To analyse in detail the mechanistic pathways taking place
during the encapsulation process, we have investigated an
equimolar mixture of 1 and anthracene through temperature-
dependent UV/Vis experiments in water. At low temperature
and similarly to tetracene, slight spectral changes are observed
upon encapsulation, as most of the diagnostic maxima of an-
thracene (for comparison see the UV/Vis spectrum of anthra-
cene in THF in Figure 7a) overlap with the absorption of the
OPE fragments between 250 and 400 nm (see blue spectrum
in Figure 7a). Nevertheless, a clear shoulder at approximately
400 nm that corresponds to the anthracene moiety can be dis-
tinguished, which supports the effective solubilisation of the
guest. The absorption maxima of encapsulated anthracene, de-
termined by subtracting the spectrum of 1 from the 1:1 1/an-
thracene mixture, is around 20 nm red-shifted compared to
those in pure THF (inset of Figure S23 in the Supporting Infor-
To our surprise, the co-assembly mechanism of anthracene
proved to be significantly different when an equimolar mixture
of 1 and anthracene was slowly cooled down from 338 to
278 K (rate=0.5 Kminꢁ1) at four different concentrations (1–4ꢄ
10ꢁ5 m, Figures S24 and S25 in the Supporting Information). In
sharp contrast to the behaviour of tetracene, the plot of frac-
tion of aggregated molecules (aagg) against temperature for all
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concentrations at 555 nm is non-sigmoidal in shape, suggest-
ing a cooperative co-assembly process (inset in Figure 7a and
Figure S25). The cooling curve has been analysed by applying
the nucleation–elongation model developed by ten Eikelder,
Markvoort, Meijer and co-workers.[30] This mechanism assumes
that after an initial thermodynamically unfavourable dimeriza-
tion process (nucleation) described by an association constant
K2, a highly favourable cooperative growth (elongation) with
a much larger binding constant (K) takes place. Application of
this model to our experimental data allows us to calculate the
thermodynamic parameters of the co-assembly process
(Table 4), and demonstrates that the encapsulation of anthra-
DLS (Figure S27 in the Supporting Information). These associ-
ates are most likely formed by strong p–p stacking between
the OPE segments and the aromatic guest units, further stabi-
lized by hydrogen bonding between the TEG chains and sur-
rounding water molecules, as shown in Scheme 2. The smallest
aggregates (6–7 nm) perfectly match the length of the OPE-
BODIPY derivative 1 whereas the largest ones (15–20 nm)
appear to arise as a result of the agglomeration of individual
micelles into larger clusters. TEM images are in perfect agree-
ment with cryo-SEM studies, and regular spherical associates
with diameters between 6 and 20 nm can be observed (Fig-
ure 7b and c and Figure S28 in the Supporting Information).
Conclusion
Table 4. Thermodynamic parameters K2, K, s, Te, DH8, DH8nucl and DS8 obtained from
temperature-dependent UV/Vis experiments of 1 and one equivalent of anthracene
(water, l=555 nm) on the basis of the ten Eikelder–Markvoort–Meijer model.
In summary, we have described the self-assembly of
a new amphiphilic oligophenyleneethynylene (OPE)-
BODIPY derivative into fibrous aggregates in water. A
wide range of experimental techniques (1D and 2D
NMR spectroscopy, UV/Vis spectroscopy, fluorescence
spectroscopy, DLS, Cryo-SEM and theoretical calcula-
tions) demonstrate the formation of extended H-type
aggregates in water and acetonitrile driven by p–p
and hydrophobic interactions. For the first time, the
detailed thermodynamic analysis of an aqueous
Conc.
[m]
DH8nucl
DH8
DS8
Te
[K]
K2
K
s
[kJmolꢁ1
]
[kJmolꢁ1
]
[Jmolꢁ1 Kꢁ1
]
[mꢁ1
]
[mꢁ1
]
1ꢄ10ꢁ5 ꢁ19.12
2ꢄ10ꢁ5 ꢁ14.22
3ꢄ10ꢁ5 ꢁ23.18
4ꢄ10ꢁ5 ꢁ35.00
ꢁ82.77
ꢁ79.89
ꢁ80.28
ꢁ65.93
ꢁ153
ꢁ152
ꢁ155
ꢁ114
332.2
1400 3.1ꢄ106 4.5ꢄ10ꢁ4
330.9 4000
331.8 78
333.0 0.3
1.2ꢄ106 3.2ꢄ10ꢁ3
9.0ꢄ105 8.7ꢄ10ꢁ5
4.1ꢄ105 7.3ꢄ10ꢁ7
cene is cooperative. This intriguing guest-dependent change in
the encapsulation mechanism anticipates that upon addition
of anthracene new aggregates with a higher degree of organi-
zation should be formed, as cooperative effects often lead to
supramolecular structures with a higher degree of internal
order compared to non-cooperative counterparts.[13]
supramolecular polymer based on a BODIPY derivative has
been reported. The interior of the resulting fibre-like associates
provides an ideal hydrophobic environment for the entrap-
ment of aromatic guest molecules driven by the hydrophobic
effect. Upon encapsulation of tetracene, the flexibility of the
fibres is reduced due to increased p–p and hydrophobic inter-
actions between host and guest, resulting in a non-cooperative
co-assembly process as demonstrated by detailed analysis of
the UV/Vis spectral changes and supported by DLS and SEM
studies. Surprisingly, the encapsulation of a slightly smaller aro-
matic guest (anthracene) under the same conditions turned
out to be significantly different, as its co-assembly mechanism
with 1 is a highly cooperative process. According to our analy-
sis of titration and temperature-dependent UV/Vis studies, this
process can be divided in three steps: at high temperatures
the most favourable event is the binding of tetracene by the
monomeric units of 1, helping them to become soluble in
water. These 1:1 complexes then dimerize when the tempera-
ture is decreased (nucleation) and ultimately elongate in
a much more favourable step into spherical nanoparticles of
7–15 nm size in which the anthracene units are encapsulated
in the interior, as demonstrated by microscopy studies (SEM,
TEM) and DLS. This change in the co-assembly mechanism
may be attributed to the fact that the molecules of 1 can no
longer be fixed in a preferred direction as a result of decreased
p–p interactions by addition of a smaller guest, leading to
more stable, discrete assemblies. Our results bring to light that
subtle changes in the molecular structure of the guest can
lead to a significant modification of the co-assembly mecha-
nism and, in turn, the resulting morphology of the co-aggre-
gates. The application of some of these concepts to control
the encapsulation and release of guest molecules might be rel-
On the basis of these data, the nucleation constant is con-
siderably (103–105-fold) smaller than the elongation constant,
indicating a high degree of cooperativity in the co-assembly
process. To better understand this complex behaviour, we
have compared the values of binding constant of anthracene
with 1 and the binding constant of the elongation step at
a concentration of 4ꢄ10ꢁ5 m. At this concentration, the Ka as-
sociated to anthracene binding (8ꢄ105 mꢁ1) is slightly higher
than that of the elongation of the co-assembled structure (4ꢄ
105 mꢁ1). According to these results, heating of the 1:1 mixture
of 1 and anthracene initially leads to the disassembly of the
supramolecular co-assembled structures, which then release
the molecules of 1 and anthracene as bound complexes. These
species (possibly dimers based on UV/Vis analysis using the ten
Eikelder model) formed by 1 and anthracene could be consid-
ered to be the monomeric units that finally form the supra-
molecular aggregate in a further elongation step (Scheme 2).
The influence of the co-assembly mechanism on the aggre-
gate morphology has been investigated by SEM and TEM
imaging. It is clear that the existence of cooperative effects in
the co-assembly of anthracene should be reflected in aggre-
gates with a distinctly new morphology. In fact, cryo-SEM
images (Figure S26 in the Supporting Information) of 1 and
one equivalent of anthracene reveal the formation of relatively
monodisperse spherical nanoparticles with diameters between
7–15 nm, which are in agreement with the values observed by
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evant to design biocompatible drug delivery systems in the
near future.
Cryo-HRSEM
The sample 1 in water was applied to copper sample stage mount-
ed to stub shuttle device. Prior to examination, the specimen was
plunged into slush (mixture of solid/liquid nitrogen) and rapidly
frozen. The sample was transferred in a sealed vacuum transfer
device to the precooled stage of the preparation chamber
(Quorum PP2000T) which is mounted on to the SEM. Controlled
freeze-drying of the fractured surface was performed for 2 min at
a temperature of ꢁ958C and at a pressure of pꢀ10–6 mbar. The
specimen was cooled to ꢁ1508C again and transferred into a SEM
sample chamber maintained at about ꢁ1508C. Images of the
sample were taken using a Zeiss Ultra plus field emission scanning
electron microscope operated at 1 kV with an aperture size set to
10 mm to avoid excessive charging and radiation damage of the
areas imaged.
Experimental Section
General methods
All solvents were dried according to standard procedures. Re-
agents were used as purchased. All air-sensitive reactions were car-
ried out under argon atmosphere. Flash chromatography was per-
formed using silica gel (Merck Silica 60, particle size 0.04–
0.063 nm). Analytical thin layer chromatography (TLC) was per-
formed on ALUGRAM Xtra SIL G/UV254 sheets supplied by Macher-
ey–Nagel. NMR spectra were recorded on a Bruker Avance 400
(1H: 400 MHz; 13C: 100.6 MHz) or Bruker DMX 600 MHz spectrom-
eter using partially deuterated solvents as internal standards. Cou-
pling constants (J) are denoted in Hz and chemical shifts (d) in
ppm. Multiplicities are denoted as follows: s=singlet, d=doublet,
t=triplet, m=multiplet. MALDI-TOF mass spectrometry was per-
formed on an autoflex II instrument (Bruker Daltronik GmbH) in
positive mode with a DCTB matrix. A microTOF focus instrument
(Bruker Daltronik GmbH) was used to perform high resolution ESI-
TOF mass spectrometry positive mode with chloroform/acetonitrile
1:1 for 4-(3,4,5-tris(triethyleneglycolmethylether)phenylethynyl)phe-
nylethynyl)triisopropylsilane and 5-(4-ethynylphenylethynyl)-1,2,3-
tris(triethyleneglycolmethylether)benzene and acetonitrile for com-
pound 1 as solvents.
TEM
TEM measurements were performed on a Siemens Elmiskop 101
Electron Microscope, operating at an acceleration voltage of 80–
100 kV. For the observation of aggregates, a drop of sample solu-
tion was placed on 400-mesh formvar copper grids coated with
carbon. Negative staining was performed by addition of a drop of
uranyl acetate aqueous solution (0.5%) onto the copper grid.
Synthetic details and characterization
1-Bromo-4-(trimethylsilylethynyl)benzene, (4-(trimethylsilylethynyl)-
phenylethynyl)triisopropylsilane,
((4-ethynylphenyl)ethynyl)triiso-
propylsilane, 5-bromo-1,2,3-tris(2-(2-(2-methoxyethoxy)ethoxy)eth-
oxy)benzene, 4-(3,4,5-tris(triethyleneglycolmethylether)phenylethy-
UV/Vis and fluorescence spectroscopy
For all spectroscopic measurements, spectroscopic grade solvents
(Uvasol) from Merck were used. The standard UV/Vis measure-
ments were carried out on a PerkinElmer Lambda 35 at room tem-
perature. l is denoted in nm and e in mꢁ1 cmꢁ1. The steady-state
fluorescence spectra were recorded on a PTI QM4–2003 fluores-
cence spectrometer and corrected against photomultiplier (type
R928) and lamp intensity of the 75 W Xenon lamp (type Ushio
UXL-75 XE). The fluorescence quantum yield was determined as
the average value for three different excitation wavelengths using
N,N’-di(2,6-diisopropylphenyl)-1,6,7,12-tetraphenoxyperylene-
3,4:9,10-tetracarboxylic acid bisimide as reference (FF)=0.96 in
CHCl3) by applying high dilution conditions (A<0.05).
nyl)phenylethynyl)triisopropylsilane,
1,2,3-tris(triethyleneglycolmethylether)benzene,
5-(4-ethynylphenylethynyl)-
4,4-difluoro-
1,3,5,7,8-pentamethyl-4-bora-3a,4a-diaza-s-indacene and 4,4-di-
fluoro-2,6-diiodo-1,3,5,7,8-pentamethyl-4-bora-3a,4a-diaza-s-inda-
cene were prepared following reported synthetic procedures and
showed identical spectroscopic properties to those reported
therein.[19,20]
Amphiphilic OPE-BODIPY (1): 62.6 mg (121.8 mmol, 1 equiv) 4,4-di-
fluoro-2,6-diiodo-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene,
176.4 mg (256 mmol, 2.1 equiv) 5-(4-ethynylphenylethynyl)-1,2,3-
tris(triethyleneglycolmethylether)benzene, 7.04 mg (6.10 mmol,
0.05 equiv) tetrakis-(triphenylphosphine)palladium(0),
2.32 mg
(12.18 mmol, 0.03 equiv) copper(I) iodide and 100.12 mL (732 mmol,
74.0 mg, 6 equiv) triethylamine were combined in 10 mL millipore
water. The suspension was degassed and flushed with argon five
times. Then, the reaction mixture was heated to 708C and stirred
while the colour changed from red to deep purple. After three
hours, the complete consumption of the starting material was
monitored by TLC. Afterwards, the reaction mixture was extracted
with 150 mL dichloromethane and the organic layer dried over
MgSO4. The solvent was removed under reduced pressure and the
crude product purified by column chromatography (silica gel,
CHCl3/MeOH 98:2, Rf =0.16). The purified product was dried by lyo-
philization of a water/dioxane solution giving a deep purple solid
DLS
DLS measurements were performed at room temperature on
a Beckman Coulter N5 submicron particle analyzer equipped with
a 25 mW Helium-Neon Laser (632.8 nm) using 10 mm Hellma
quartz cuvettes and spectroscopic grade solvents.
SEM
SEM imaging was performed on a Carl Zeiss Microscope Ultra plus
field emission scanning electron microscope (FESEM) equipped
with a GEMINIꢆ e-Beam column (Carl Zeiss NTS GmbH) operating
at an accelerating voltage of 1–3 kV with an aperture size set from
30 kV to 7 or 10 mm to avoid excessive charging and radiation
damage of the samples imaged. The sample was prepared by plac-
ing a drop of the solution of 1 and one equivalent of tetracene in
water onto a silicon wafer, removing the solvent with filter paper
and placing a drop of silver ink onto the sample.
1
(114 mg, 68.6 mmol, yield: 57%). H NMR (400 MHz, CD3CN, 298 K):
d=7.52 (m, 8H, Hd), 6.85 (s, 4H, He), 4.15 (m, 12H, Hf), 3.82 (m, 8H,
Hg), 3.74 (m, 4H, Hg’), 3.70–3.47 (m, 48H, Hhꢁk), 3.32 (s, 6H, Hl’), 3.31
(s, 12H, Hl), 2.70 (s, 3H, Ha), 2.66 (s, 6H, Hc), 2.57 ppm (s, 6H, Hb);
13C NMR (100.6 MHz, CD3CN, 298 K): d=157.0, 153.6, 145.3, 143.7,
140.1, 132.9, 132.3, 132.1, 129.1, 124.0, 123.6, 116.3, 111.5, 97.0,
92.2, 88.8, 84.5, 73.3, 72.6, 71.4, 71.3, 71.2, 71.1, 71.0, 70.3, 69.7,
58.9, 17.7, 16.3, 13.8 ppm (t, 4J(C,F)=2.56 Hz); MALDI-TOF: m/z=
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1634.83; HRMS (ESI)+ (acetonitrile): m/z calcd for [C88H121BF2N3O24]+:
1651.8432; found: 1651.8448 [M+NH4]+; UV/Vis (CH2Cl2): lmax (e)=
570 (88300), 340 (68500); fluorescence quantum yield (FF) in
CH2Cl2 =0.67.
[12] a) K. Wunderlich, A. Larsen, J. Marakis, G. Fytas, M. Klapper, K. Mꢇllen,
Small 2014, 10, 1914–1919; b) A. Das, S. Ghosh, Angew. Chem. 2014,
126, 2068–2084; Angew. Chem. Int. Ed. 2014, 53, 2038–2054; c) B. Nar-
ayan, S. P. Senanayak, A. Jain, K. S. Narayan, S. J. George, Adv. Funct.
Mater. 2013, 23, 3053–3060; d) L. Chen, K. S. Mali, S. R. Puniredd, M.
Baumgarten, K. Parvez, W. Pisula, S. De Feyter, K. Muellen, J. Am. Chem.
Soc. 2013, 135, 13531–13537; e) D. Gçrl, X. Zhang, F. Wꢇrthner, Angew.
Chem. 2012, 124, 6434–6455; Angew. Chem. Int. Ed. 2012, 51, 6328–
6348; f) J. B. Matson, S. I. Stupp, Chem. Commun. 2012, 48, 26–33;
g) M. J. Mayoral, G. Fernandez, Chem. Sci. 2012, 3, 1395–1398; h) H.-J.
Kim, T. Kim, M. Lee, Acc. Chem. Res. 2011, 44, 72–82; i) W. Zhang, W. Jin,
T. Fukushima, A. Saeki, S. Seki, T. Aida, Science 2011, 334, 340–343; j) J.-
H. Ryu, D.-J. Hong, M. Lee, Chem. Commun. 2008, 1043–1054.
[13] T. Aida, E. W. Meijer, S. I. Stupp, Science 2012, 335, 813–817.
[14] a) S. S. Babu, V. K. Praveen, A. Ajayaghosh, Chem. Rev. 2014, 114, 1973–
2129; b) J. A. Foster, J. W. Steed, Angew. Chem. 2010, 122, 6868–6874;
Angew. Chem. Int. Ed. 2010, 49, 6718–6724; c) J. A. Foster, M. Piepen-
brock Marc-Oliver, G. O. Lloyd, N. Clarke, A. K. Howard Judith, J. W.
Steed, Nat. Chem. 2010, 2, 1037–1043; d) N. M. Sangeetha, U. Maitra,
Chem. Soc. Rev. 2005, 34, 821–836.
[15] a) C. Rest, M. J. Mayoral, G. Fernandez, Int. J. Mol. Sci. 2013, 14, 1541–
1565; b) M. R. Molla, S. Ghosh, Chem. Eur. J. 2012, 18, 9860–9869; c) T.
Emiliano, P. Nandhini, G. D. Pantos¸, K. M. S. Jeremy, Faraday Discuss.
2010, 145, 205–218; d) K. S. Moon, H. J. Kim, E. Lee, M. Lee, Angew.
Chem. 2007, 119, 6931–6934; Angew. Chem. Int. Ed. 2007, 46, 6807–
6810; e) J.-H. Ryu, H.-J. Kim, Z. Huang, E. Lee, M. Lee, Angew. Chem.
2006, 118, 5430–5433; Angew. Chem. Int. Ed. 2006, 45, 5304–5307.
[16] a) Y. Liu, B. Liu, J. Riesberg, W. Shen, Macromol. Biosci. 2011, 11, 1325–
1330; b) C. DeForest, B. Polizzotti, K. Anseth, Nat. Mater. 2009, 8, 659–
664; c) M. Cushing, K. Anseth, Science 2007, 316, 1133–1134.
[17] Z. Huang, H. Lee, E. Lee, S. K. Kang, J. M. Nam, M. Lee, Nat. Commun.
2011, 2, 459.
Acknowledgements
We are thankful to Prof. Frank Wꢇrthner for many helpful dis-
cussions, Ana Reviejo for graphic design and the Humboldt
Foundation for financial support (Sofja Kovalevskaja Award).
Keywords: amphiphiles
·
aqueous
self-assembly
·
encapsulation · supramolecular polymerization · p-conjugated
systems
[1] a) A. B. Nepomnyashchii, A. J. Bard, Acc. Chem. Res. 2012, 45, 1844–
1853; b) G. Ulrich, R. Ziessel, A. Harriman, Angew. Chem. 2008, 120,
1202–1219; Angew. Chem. Int. Ed. 2008, 47, 1184–1201; c) A. Loudet, K.
Burgess, Chem. Rev. 2007, 107, 4891–4932.
[2] N. Boens, V. Leen, W. Dehaen, Chem. Soc. Rev. 2012, 41, 1130–1172.
[3] For recent examples see: a) K. K. Jagtap, N. Shivran, S. Mula, D. B. Naik,
S. K. Sarkar, T. Mukherjee, D. K. Maity, A. K. Ray, Chem. Eur. J. 2013, 19,
702–708; b) Y. Xiao, D. Zhang, X. Qian, A. Costela, I. Garcia-Moreno, V.
Martin, M. E. Perez-Ojeda, J. BaÇuelos, L. Gartzia, I. Lopez Arbeloa, Chem.
Commun. 2011, 47, 11513–11515.
[4] a) S.-L. Niu, C. Massif, G. Ulrich, P.-Y. Renard, A. Romieu, R. Ziessel, Chem.
Eur. J. 2012, 18, 7229–7242; b) S.-L. Niu, C. Massif, G. Ulrich, R. Ziessel,
P.-Y. Renard, A. Romieu, Org. Biomol. Chem. 2011, 9, 66–69.
[18] Metal-Catalyzed Cross-Coupling Reactions (Eds.: F. Diederich, P. J. Stang),
Wiley-VCH, Weinheim, 1998.
[19] T. Yogo, Y. Urano, Y. Ishitsuka, F. Maniwa, T. Nagano, J. Am. Chem. Soc.
2005, 127, 12162–12163.
[20] C. Rest, M. J. Mayoral, K. Fucke, J. Schellheimer, V. Stepanenko, G.
Fernꢂndez, Angew. Chem. 2014, 126, 716–722; Angew. Chem. Int. Ed.
2014, 53, 700–705.
[21] M. Kasha, H. R. Rawls, M. Ashraf El-Bayoumi, Pure Appl. Chem. 1965, 11,
371–392.
[22] a) Q. Chu, Y. Pang, Macromolecules 2005, 38, 517–520; b) A. Beeby, K.
Findlay, P. J. Low, T. B. Marder, J. Am. Chem. Soc. 2002, 124, 8280–8284;
c) M. Levitus, K. Schmieder, H. Ricks, K. D. Shimizu, U. H. F. Bunz, M. A.
Garcꢀa-Garibay, J. Am. Chem. Soc. 2001, 123, 4259–4265.
[5] a) A. Kamkaew, S. H. Lim, H. B. Lee, L. V. Kiew, L. Y. Chung, K. Burgess,
Chem. Soc. Rev. 2013, 42, 77–88; b) N. Adarsh, R. R. Avirah, D. Ramaiah,
Org. Lett. 2010, 12, 5720–5723.
[6] a) T. Bura, N. Leclerc, S. Fall, P. LꢁvÞque, T. Heiser, P. Retailleau, S. Rihn, A.
Mirloup, R. Ziessel, J. Am. Chem. Soc. 2012, 134, 17404–17407; b) Y. Hay-
ashi, N. Obata, M. Tamaru, S. Yamaguchi, Y. Matsuo, A. Saeki, S. Seki, Y.
Kureishi, S. Saito, S. Yamaguchi, H. Shinokubo, Org. Lett. 2012, 14, 866–
869; c) S. Kolemen, O. A. Bozdemir, Y. Cakmak, G. Barin, S. Erten-Ela, M.
Marszalek, J.-H. Yum, S. M. Zakeeruddin, M. K. Nazeeruddin, M. Grꢈtzel,
E. U. Akkaya, Chem. Sci. 2011, 2, 949–954; d) S. Kolemen, Y. Cakmak, S.
Erten-Ela, Y. Altay, Y. Brendel, M. Thelakkat, E. U. Akkaya, Org. Lett. 2010,
12, 3812–3815.
[7] a) B. Rybtchinski, ACS Nano 2011, 5, 6791–6818; b) A. P. H. J. Schenning,
E. W. Meijer, Chem. Commun. 2005, 3245–3258.
[23] F. C. Spano, Acc. Chem. Res. 2010, 43, 429–439.
[24] C. Reichardt, Chem. Rev. 1994, 94, 2319–2358.
[8] a) I. Mikhalyov, N. Gretskaya, F. BergstrÅm, L. B.-ꢅ. Johansson, Phys.
Chem. Chem. Phys. 2002, 4, 5663–5670; b) D. Tleugabulova, Z. Zhang,
J. D. Brennan, J. Phys. Chem. B 2002, 106, 13133–13138.
[9] a) A. Florian, M. J. Mayoral, V. Stepanenko, G. Fernꢂndez, Chem. Eur. J.
2012, 18, 14957–14961; b) H. Liu, J. Mack, Q. Guo, H. Lu, N. Kobayashi,
Z. Shen, Chem. Commun. 2011, 47, 12092–12094; c) A. Nagai, K.
Kokado, J. Miyake, Y. Chujo, Macromolecules 2009, 42, 5446–5452; d) A.
Nagai, J. Miyake, K. Kokado, Y. Nagata, Y. Chujo, J. Am. Chem. Soc. 2008,
130, 15276–15278.
[10] a) L. Gai, H. Lu, B. Zou, G. Lai, Z. Shen, Z. Li, RSC Adv. 2012, 2, 8840–
8846; b) J.-H. Olivier, J. Barberꢂ, E. Bahaidarah, A. Harriman, R. Ziessel, J.
Am. Chem. Soc. 2012, 134, 6100–6103; c) M. Benstead, G. A. Rosser, A.
Beeby, G. H. Mehl, R. W. Boyle, New J. Chem. 2011, 35, 1410–1417; d) S.
Frein, F. Camerel, R. Ziessel, J. Barberꢂ, R. Deschenaux, Chem. Mater.
2009, 21, 3950–3959; e) F. Camerel, G. Ulrich, J. Barberꢂ, R. Ziessel,
Chem. Eur. J. 2007, 13, 2189–2200; f) F. Camerel, L. Bonardi, G. Ulrich, L.
Charbonniere, B. Donnio, C. Bourgogne, D. Guillon, P. Retailleau, R. Zies-
sel, Chem. Mater. 2006, 18, 5009–5021; g) F. Camerel, L. Bonardi, M.
Schmutz, R. Ziessel, J. Am. Chem. Soc. 2006, 128, 4548–4549.
[11] For examples of BODIPY-based nanoparticle assemblies in water, see:
a) J.-H. Olivier, J. Widmaier, R. Ziessel, Chem. Eur. J. 2011, 17, 11709–
11714; b) Y. Tokoro, A. Nagai, Y. Chujo, Tetrahedron Lett. 2010, 51, 3451–
3454.
[25] K. Rurack, “Fluorescence Quantum Yields: Methods of Determination
and Standards” in Springer Series on Fluorescence Vol. 5 (Ed.: U. Resch-
Genger), Springer-Verlag, Berlin Heidelberg, 2008, pp. 101–145.
[26] a) A. Nagai, K. Kokado, J. Miyake, Y. Chujo, J. Polym. Sci. Part A 2010, 48,
627–634; b) T. Hirose, K. Matsuda, Chem. Commun. 2009, 5832–5834.
[27] a) M. M. Smulders, M. M. L. Nieuwenhuizen, T. F. A. De Greef, P. van der
Schoot, A. P. H. J. Schenning, E. W. Meijer, Chem. Eur. J. 2010, 16, 362–
367; b) T. F. A. de Greef, M. M. J. Smulders, M. Wolffs, A. P. H. J. Schen-
ning, R. P. Sijbesma, E. W. Meijer, Chem. Rev. 2009, 109, 5687–5754.
[28] G. Fernꢂndez, M. Stolte, V. Stepanenko, F. Wꢇrthner, Chem. Eur. J. 2013,
19, 206–217.
[29] F. Garcꢀa, L. Sꢂnchez, Chem. Eur. J. 2010, 16, 3138–3146.
[30] a) H. M. M. ten Eikelder, A. J. Markvoort, T. F. A. de Greef, P. A. J. Hilbers,
J. Phys. Chem. B 2012, 116, 5291–5301; b) A. J. Markvoort, H. M. M. ten
Eikelder, P. A. J. Hilbers, T. F. A. de Greef, E. W. Meijer, Nat. Commun.
2011, 2, 509–517.
Received: February 7, 2014
Published online on July 14, 2014
Chem. Eur. J. 2014, 20, 10669 – 10678
www.chemeurj.org
10678
ꢃ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim