A fluorescent, shape-persistent dendritic host with photoswitchable guest encapsulation and intramolecular energy transfer

Article abstract of DOI:10.1021/ja2022398

A fluorescent and photoresponsive host based on rigid polyphenylene dendrimers (PPDs) has been synthesized. The key building block for the divergent dendrimer buildup is a complex tetracyclone 12 containing azobenzenyl, pyridyl, and ethynyl entities. The

Full text of DOI:10.1021/ja2022398

ARTICLE
pubs.acs.org/JACS
A Fluorescent, Shape-Persistent Dendritic Host with Photoswitchable
Guest Encapsulation and Intramolecular Energy Transfer
Thi-Thanh-Tam Nguyen, David T €u rp, Dapeng Wang, Belinda N €o lscher, Fr ꢀe d ꢀe ric Laquai, and Klaus M €u llen*
Max-Planck-Institute for Polymer Research, Ackermannweg 10, D-55128 Mainz, Germany
S Supporting Information
b
ABSTRACT: A fluorescent and photoresponsive host based on rigid polyphenylene
dendrimers (PPDs) has been synthesized. The key building block for the divergent
dendrimer buildup is a complex tetracyclone 12 containing azobenzenyl, pyridyl, and
ethynyl entities. The rigidity of polyphenylenes is of crucial importance for a site-
specific placement of different functions: eight azobenzene (AB) moieties into the rigid
scaffold, a fluorescent perylenetetracarboxdiimide (PDI) into the core, and eight
pyridin functions into the interior cavities. AB moieties of hostꢀ1 undergo reversible
cisꢀtrans photoisomerization and are photostable, as confirmed by various techniques:
1
UVꢀvis, H NMR, size exclusion chromatography, and fluorescence correlation
(FCS). In this system, AB moieties act as photoswitchable hinges and enable control
over (i) molecular size, (ii) intramolecular energy transfer between AB and PDI, and
(
iii) encapsulation and release of guest molecules. The presence of PDI allows not only
following the effect of cisꢀtrans photoisomerization on molecular size with highly sensitive FCS but also monitoring the efficiency
of the intramolecular energy transfer process (from AB to PDI) by time-resolved optical spectroscopy. Pyridyl functions were
incorporated to facilitate guest uptake via hydrogen bonds between the host and guests. Also, we have demonstrated that the
photoswitchability of the host can be utilized to actively encapsulate guest molecules into its interior cavities. This novel, light-driven
encapsulation mechanism could enable the design of new drug delivery systems.
4
2,43
1. INTRODUCTION
It is known that polyphenylene dendrimers (PPDs)
are
rigid and shape-persistent. These properties prevent them from
collapsing and thus their interior voids are permanently main-
tained. In previous work of our group, AB was successfully used
as a PPD core. The resulting dendrimer exhibits a significant
conformational change upon cisꢀtrans photoisomerization. Thus,
it was expected that the introduction of several AB moieties into
specific sites of a rigid PPD scaffold would amplify the effect of
size and shape change.
Here, we aim to design a photoswitchable dendritic host based
on PPDs. The photoswitching should be driven by the cisꢀtrans
photoisomerization of ABs. The system should be able to both
physically encapsulate guest molecules and release them by way
of drastically changing its overall shape: a “closed” structure of
the host would encapsulate guest molecules permanently until a
change to an “open” structure would allow the release of guests
from its interior (Figure 1).
The system presented herein should serve as an organosoluble
model for investigating the effect of AB isomerization on the
change of dendrimer shape and guest encapsulation/release as
well as a model system for photoswitching of intramolecular
energy transfer processes. Also, the proposed mechanism has
implications for the design of new dendritic drug delivery systems.
Usually, drugs are covalently linked to their hosts in order to
Macromolecules that are responsive to an external stimulus in
a controlled and reproducible manner have many potential
1
ꢀ14
applications.
They allow one to reversibly manipulate and
44
change molecular properties such as shape, conformation, or
13
polarity whenever desired. Especially the cisꢀtrans photoi-
somerization of azobenzene (AB) continues to attract tremen-
15
dous interest since its discovery in the late 1930s. Owing to its
photostability and the substantial geometrical change accompa-
nying cisꢀtrans isomerization, AB has enabled the development
of a variety of photoresponsive functional materials and devices,
7
,9
10
including smart polymers, molecular machines, and molec-
8
ular switches. There have been attempts to combine the
conformational switchability of AB with the structural perfect-
16ꢀ24
ness and multivalency of dendrimers.
Dendrimers define an
active field of research because of their many unique prop-
2
5ꢀ35
erties,
the use as hosts in advanced drug delivery systems.
which also make them preferential candidates for
3
6ꢀ41
Since
then, the number of papers concerning dendritic hostꢀguest
systems has been continuing to increase. V €o gtle et al. reported
that the peripheral decoration of a polypropyleneamine dendri-
mer with 32 AB moieties enables changing the permeability of
18
the dendritic shell toward guest molecules. However, due to the
flexibility of most types of dendrons, the conformational change
of AB can only affect its close molecular environment. To achieve
a pronounced photoinduced change of the overall dendritic
shape and structure remains a challenging task.
Received: March 11, 2011
Published: June 17, 2011
r 2011 American Chemical Society
11194
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|J. Am. Chem. Soc. 2011, 133, 11194–11204

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ARTICLE
more importantly, an orthogonal orientation of all substituents
(
and thus dendrons) with regard to that plane. Model structures
suggest that the rigid dendrons spatially extend into opposing
directions in the all-trans isomer (“open” structure), while point-
ing toward each other in the all-cis isomer (“closed” structure).
As a consequence, voids in the dendritic interior are easily
accessible for potential guest molecules in the “open” form, while
they are sterically shielded with rigid and bulky polyphenylene
dendrons in the “closed” form. Moreover, the model structures
suggest that a third-generation dendrimer is ideal: lower genera-
tions result in insufficient shielding of voids, while in higher
generations steric hindrance obstructs isomerization.
2. RESULTS AND DISCUSSION
2.1. Synthesis. The targeted dendritic host 1 was synthesized
in 15 steps. The key building block for its synthesis is the AB-,
ethynyl- and pyridyl-functionalized tetracyclone 12. It was pre-
pared in seven steps starting from p-bromoaniline 2 (Scheme 1).
Sonogashira coupling of (triisopropylsilyl)acetylene with p-
bromoaniline (2) afforded ethynyl-functionalized aniline 4, and
oxidation of p-bromoaniline (2) with ozone afforded nitroso-
benzene 3 in almost quantitative yield. Azo-coupling of both
products 3 and 4 yielded the asymmetrically substituted azoben-
zene 5. The selected sequential order of coupling reactions
Figure 1. Proposed mechanism for the photoswitched encapsulation
and release mechanism.
prevent premature drug leaching, while release is triggered by a
45
65
bond-breaking stimulus (usually pH). However, covalent link-
ing requires a chemical modification of the drugs, and this may
46
reduce their efficiency. In contrast, our proposed mechanism of
physical encapsulation could enable the delivery of nonlinked,
unmodified, and active drugs while still preventing them from
premature leaching.
(
route 1) avoids the necessity of performing the Sonogashira
coupling selectively (in route 2).
Boron-ester funtionalized benzil 8 was synthesized from 4,4 -
dibromobenzil 7 using an excess amount of bis(pinacolato)-
We chose to employ a perylenetetracarboxydiimide (PDI) dye
as a central fluororescent chromophore in our host model
because of its outstanding stabilities and high fluorescence
0
diboron in the presence of Pd(dppf)Cl and potassium carbo-
2
4
7ꢀ49
quantum yields
and the accumulated expertise of our group
nate. Suzuki coupling of benzil 8 and asymmetrically substituted
AB 5 then furnished the AB- and ethynyl-functionalized key
intermediate 9. It is noteworthy, however, that thorough pur-
ification of benzil 8 [removal of trace amounts of bis(pinacolato)-
diboron] prior to Suzuki coupling is crucial to avoid homocou-
pling of 5. The 1,3-dipyridin-2-ylpropan-2-one 11 was obtained
by nucleophilic addition of picolyllithium (generated from
phenyllithium and 2-picoline) to 2-pyridylacetonitrile followed
regarding the dendronization of bay functionalized PDIs with
50
rigid polyphenylenes.
Additionally, the highly fluorescent PDI in the core of the
dendrimer is a very effective probe for intramolecular energy
transfer processes, as the combination of AB in the scaffold and
PDI in the dendrimer represents an energy transfer, i.e., donorꢀ
acceptor system. Intramolecular energy transfer in dendrimers
50ꢀ64
66
has already been reported by us and others,
but the com-
by acidic hydrolysis of the imine intermediate.
bination of a photoswitchable donor (AB) and a fluorescent
acceptor has the added value of control over the efficiency of the
intramolecular energy transfer process by switching between the
trans and cis isomer. Thus, the presented dendrimer not only serves
as a model system for studies of photoswitching of intramolecular
energy transfer processes but may also have potential applications,
for instance, as a photoswitched light-harvesting system.
Finally, the Knoevenagel condensation between AB- and
ethynyl-functionalized benzil 9 and pyridyl-functionalized pro-
panone 11 provided the key building block 12. Surprisingly, an
alternative reaction sequence via Knoevenagel condensation of
dibromobenzil 7 and dipyridinylacetone 11 was not successful.
Possibly, the solubility of dibromobenzil 7 in tert-butanol is too
low even at high temperatures.
The target dendritic host 1 (as shown in Figure 2) that has
been synthesized here fulfills the following requirements:
Ethynyl functionalization of the PDI core was achieved in
three steps starting from tetrachloro-PDI 13 following the
50
(
(
i) a rigid scaffold based on a third-generation PPD,
ii) an AB in the middle of each dendron (every AB acts as a
literature procedure. DielsꢀAlder cycloaddition of key build-
ing block 12 to the so functionalized PDI core 14 afforded the
first-generation dendrimer 15 (Scheme 2). Successive deprotec-
“
hinge” and the combination of eight “hinges” may
generate photoswitchable voids),
tion and cycloaddition with tetracyclone or Cp(TIPS) building
2
42,43
(
(
iii) basic pyridyl functions in the interior for enhancing
hostꢀguest (HꢀG) interactions,
blocks
gave the dendrimer G -end-capped 17, G -(TIPS)
2
2
16
1
8, and finally the target dendrimer 1.
All compounds were characterized by H and C NMR
1
13
iv) a fluorescent chromophore to enable fluorescence track-
ing in potential cell experiments (for our ultimate pur-
pose being an aqueous drug delivery system), and
v) an energy donorꢀacceptor system consisting of AB as donor
and PDI as acceptor allowing control of intramolecular
energy transfer processes by photoswitching of AB.
spectroscopy, MALDI-TOF mass spectrometry, UVꢀvis ab-
sorption spectroscopy, FTIR spectroscopy, melting point, and
elemental analysis. The dendrimers 1 and 15ꢀ19 were also
characterized by fluorescence emission spectroscopy (analytical
data are available in the Supporting Information).
(
The steric congestion between phenoxy groups in all four
PDI bay positions enforces a slight twisting of the PDI plane and,
2.2. The Photochemical CisꢀTrans Isomerization. With
the successful synthesis of dendrimer 1, eight AB moieties
1
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Figure 2. Chemical structure of the dendritic host 1.
have been placed into a rigid dendritic scaffold. The UVꢀvis
absorption spectrum of dendrimer 1 has three characteristic
absorption bands with maxima at 254 nm (absorption of
phenyl rings), 500ꢀ600 nm (absorption of the PDI core)
and, most importantly, at 370 nm (πꢀπ* transition of trans-
spectra before (solid black curve) and after 12 min of irradiation
(solid blue curve).
Compared to the nonirradiated solution, the absorption band
at 370 nm clearly decreases, while the absorption band at 460 nm
67
(nꢀπ* transitions of cis-AB) increases slightly. The change
of absorption band intensities induced by UV irradiation indi-
cates a conversion of the all-trans dendrimer 1(8t) into species
containing on average three trans and five cis AB moieties,
namely, 1(3t5c), in the photostationary state (PSS) (see Figure
1 of the Supporting Information ). The quantum yield of the
1(8t)f1(3t5c) photoisomerization reaction was determined to
6
7
AB). The intensity of the absorption band at 370 nm
correlates to the amount of trans-AB isomer in the solution
(
Figure 4).
ꢀ
6
A 2.5 ꢁ 10 M solution of dendrimer 1 in methylene chloride
was exposed to UV light of 365 nm in order to induce the iso-
merization of AB from trans to cis. Figure 4 shows the absorption
1
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a
a
Scheme 1. Synthesis of Key Building Block Tetracyclone 12
Scheme 2. Synthesis of 1
a
Reaction conditions: (i) Pd(PPh )Cl , (triisopropylsilyl)acetylene,
3
2
0
toluene/TEA, 80 °C, 12 h, 60%; (i ) similar to condition i but at 0 °C
to rt, 90%; (ii) 2KHSO KHSO SO4, DCM/H O, 4 h, 92%; (iii)
AcOEt/AcOH, 50 °C, 12 h; 86%, (iv) bis(pinacolato)diboron, Pd-
dppf)Cl , AcOK, dioxane, 80 °C, 24 h, argon, 90%; (v) Pd(PPh ), CuI,
PPh , nBu
lithium, reflux (b) H
5
3
4
3
K
2
2
(
2
3
3
4
NBr, toluene/H
2
O, 80 °C, argon, 93%; (vi) (a) phenyl-
+
3
O , 70%; (vii) tBuOH, nBu NOH, 80 °C, 2 h, 65%.
4
be Φt-c = 0.114 (inset of Figure 4 and Supporting Information
Figure 2). Due to the nonlinear characteristic of the apparent
quantum yield values versus times, the maximum quantum yield
was determined by extrapolating the linear region to zero time,
corresponding to the first four Φ values within the first 2 min of
the photoisomerization reaction.
The solution of 1(3t5c) was then irradiated with visible light of
4
50 nm to induce the back isomerization from cis to trans.
Consequently, the absorption band at 370 nm recovers its initial
a
Reaction conditions: (viii) o-xylene, 12, 145 °C, 24 h, 90%; (ix)
NF, THF, rt, 3 h [affords 16 (87%) or 19 (92%)]; (x) o-xylene,
6
8
intensity, indicating the back conversion of 1(3t5c)f1(8t)
with quantum yield Φc-t = 0.794 (see Supporting Information
Figure 3). Thus, UVꢀvis measurements thus demonstrate that
AB moieties can undergo reversible photoisomerization within
the rigid scaffold of dendrimer 1. Furthermore, Figure 4 shows
that the photoisomerization proceeds while maintaining isosbes-
tic points up to the PSS, which demonstrates the photostability of
AB moieties and the dendrimer upon irradiation with UV light.
By plotting the change of absorbance versus time (Supporting
Information Figure 8), the rate constant of cis-to-trans (kct)
photoisomerization of AB moieties in 1 was determined to be
nBu
4
tetracyclone, 145 °C, 48 h [affords 17 (98%) or 1 (92%)]; (xi) o-xylene,
Cp(TIPS) , 145 °C, 48 h [affords 18 (91%)].
2
with dendrimer size has also been reported for rigid dendrimers
19
using AB as the core.
Dendrimer 1 exhibits good photostability, as was confirmed by
excellent recovery of the respective isomers upon alternately
exposing a solution of 1 to light of 365 and 450 nm wavelength
69
(Figure 6).
In a sequence of 20 “switchings” between cis and trans, we
found no indication of efficiency decrease or degradation.
The structural model of 1 (Figure 3) indicates that photo-
isomerization should induce a drastic change in molecular size
and volume. To investigate the effect of photoisomerization on
the molecular size of 1, its hydrodynamic volume was determined
by means of size exclusion chromatography (SEC) before 1(8t)
and after 1(3t5c) irradiation at 365 nm.
ꢀ
1
1
.80 ( 0.18 min . In contrast to the light-driven isomerization,
the thermally driven cis-to-trans isomerization of AB moieties
within 1 (Figure 5) occurs much more slowly [k
=
ct,thermal
ꢀ4
ꢀ
4
ꢀ1
(
8.15 ( 0.40) ꢁ 10 min , only about 4.5 ꢁ 10 times the
rate constant of the light-driven process]. The small value of k
ct,
indicates that the cis conformation in 1 is maintained for a
thermal
reasonably long time (t1/2 = 14.2 h) despite relatively high steric
repulsion between dendrons.
After irradiation at 365 nm, 1 showed a significant increase in
elution volume (Figure 7), indicating a marked decrease of its
In order to examine the effect of dendron size (potential steric
obstruction) on the photoisomerization of AB, the rate constants
of trans-to-cis isomerization were also measured as a function
of dendrimer generation (from G to G at the same con-
70
hydrodynamic volume of about 40%.
To further support our findings, the changes in hydrodynamic
volume were also determined by spectroscopic methods. While
the presence of the fluorescent PDI chromophore in dendrimer 1
precluded determination of the hydrodynamic radius rH via
dynamic light scattering (DLS), it enabled the study of 1 via
fluorescence correlation spectroscopy (FCS). The latter allows
1
3
ncentration). Surprisingly, the rate constants of all dendrimers
were found to be on the same order of magnitude, which
indicates that an increasing dendron size does not substantially
impede AB isomerization. Such modest variance in rate constants
1
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Figure 5. Determination of the rate constant of thermal cis-to-trans
ꢀ
6
isomerization for a 1.5 ꢁ 10 M solution of 1(3t5c) in CH Cl2
2
obtained after being irradiated at 365 nm for 10 min. The change of
absorption intensity at 370 nm was plotted against time and fitted
exponentially to derive the rate constant.
Figure 3. Model structures of the dendritic host system in all-cis and all-
trans conformation.
Figure 6. Change in absorption of 1 at 370 nm upon 10 irradiation
7
0
cycles (alternating irradiation at 365 and 450 nm).
Figure 4. Reversible change in the absorption band of 1 at 370 nm as a
ꢀ
6
function of irradiation time at 365 and 450 nm (2.5 ꢁ 10 M solution of
1
in CH Cl at 298 K): solid black line, no irradiation; solid blue line,
2
2
PSS reached after 720 s of exposure to 365 nm light; dashed curves,
absorption changes with time upon being exposed to 365 nm UV light;
solid red line, PSS solution after 300 s of exposure to 450 nm light;
6
8
Figure 7. SEC traces of solutions of 1 before and after 10 min of
4
inset, apparent quantum yield values as a function of time, where the
extrapolation of quantum yield values of the first two minutes to zero
time is used for determining the real quantum yield of the trans f cis
process of 1 (for the quantum yield of the cis-to-trans process see the
Supporting Information).
exposure to 365 nm light. Conditions: THF, 1 mL/min, 500 Å, 10 Å,
6
10 Å SDV (Polymer Standard Service Mainz) columns (0.8 ꢁ 30 cm),
ambient temperature.
determination of the diffusion properties of fluorescent tracers
with extremely high sensitivity down to the single molecule level,
and with higher precision compared to DLS.
ꢀ7
A highly diluted solution (10 M) of 1 in CH Cl was
2
2
excited by a 543 nm laser. This wavelength matches the absor-
bance of the PDI core and does not influence the photoiso-
merization of AB.
FCS measurements (Figure 8) clearly show a decrease in
diffusion time of dendrimer 1 after irradiation at 365 nm
Figure 8. FCS results: normalized autocorrelation functions of 1 before
(transfcis), which corresponds to a drastic decrease of
ꢀ7
(blue) and after 10 min of exposure to 365 nm light (red) (solution 10
M
the hydrodynamic radius from 3.59 ( 0.19 nm before
of 1 CH Cl ).
2
2
irradiation to 2.49 ( 0.09 nm after irradiation. These radii
3
correspond to volumes of 194 and 65 nm , respectively, and
7
1
thus a volume decrease of about 66%. Such pronounced
yet been reported. This result proves that the rigidity of
decrease in volume upon cisꢀtrans isomerization has not
the dendritic scaffold and the specific positioning of ABs
1
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Figure 9. (Top) Molecular structure of 1 with some peak assignmen.
1
(
(
Bottom) Partial H NMR spectrum of 1(8t) (red) and 1(3t5c) (blue)
2 2
700 MHz, CD Cl , 295 K).
Figure 10. The upper panel shows the absorption and fluorescence
spectra of 1(8t) (blue) and 1(3t5c) (red). The emission spectra were
recorded after excitation at 570 nm. The lower panel shows the PL decay
transients (dots) for 1(3t5c). and 1(8t) and single exponential fits (solid
lines).
therein are crucial for a drastic change of dendrimer size
upon photoswitching.
The model structures (Figure 3) indicate that dendrimer 1
becomes much more compact upon switching from the trans to
the cis isomer. In the cis isomer, protons of both the core and
dendrons should be noticeably shielded by densely packed
polyphenylenes in their close environment as compared to the
trans isomer. To detect such changes in the chemical environ-
Table 1. Photoluminescence Quantum Efficiencies (PLQE)
of 1(8t) and cis-1 Excited at 550 nm (i.e., PDI absorption) and
365 nm (i.e., absorption of the azo group)
1
ment of specific protons, H NMR spectra of dendrimer 1 were
550 nm
365 nm
recorded before and after irradiation at 365 nm (Figure 9 and
7
2
Supporting Information Figure 4).
1(8t)
(3t5c)
≈1
0.34 ( 0.10
0.30 ( 0.10
0.37 ( 0.10
1
The H NMR spectrum of dendrimer 1 after irradiation
1(3t5c), blue] shows two major differences as compared to
1
[
the spectrum before irradiation [1(8t), red].
First, in 1(3t5c), many proton signals (H , HPDI, Hazo
,
this is, to the best of our knowledge, the first example of
photoswitching of intramolecular energy transfer within a den-
dritic structure from AB to PDI. Previous work, for instance by
Feng and co-workers on linear perylenediimideꢀazobenzene
dyads, has demonstrated a conformation-related change of the
fluorescence efficiency due to PDI excimer formation, if PDI
molecules come close enough in one of the isomers.
Figure 10 shows a comparison of the absorption and fluores-
cence spectra of 1(8t) and 1(3t5c). The absorption maximum of
1(3t5c) at 370 nm is about half of that of 1(8t) at 370 nm. The
fluorescence spectra obtained upon direct excitation of the PDI
core at 570 nm are virtually the same for 1(3t5c) and 1(8t).
However, the emission intensity of 1(3t5c) is much lower than
that observed for 1(8t), despite similar absorption at 570 nm. We
determined the photoluminescence quantum efficiency (PLQE)
of 1(8t) and 1(3t5c) in solution, as shown in Table 1.
py
Hperiphery) experience a slight upfield shift, probably due to better
local screening from the overall magnetic field by surrounding
polyphenylenes. Indeed, it was indicated previously that some
azo groups remain in the trans form; thus, there should be some
signals due to the trans form, and this trans form should create a
different environment for some cis azo groups. Also, specific
protons give rise to more than one defined signal in 1(3t5c) as
compared to 1(8t), which may be due to the simultaneous
existence of slightly different environments for such protons in
76
1
different 1(3t5c) conformers. H NMR spectra thus clearly
reflect the increased density of polyphenylenes surrounding the
dendritic core after irradiation at 365 nm. The switchability of
polyphenylene density around the dendritic core is an important
prerequisite to enable active encapsulation of guest molecules
into internal cavities of 1.
2
.3. Photoswitchable Intramolecular Energy Transfer. The
The PLQE of 1(8t) upon excitation of the PDI core at 550 nm
is unity within the experimental error, whereas a substantially
lower quantum efficiency of 34% is found for 1(3t5c). Thus, it
appears that the steric crowding in 1 (3t5c) decreases the PLQE
of the PDI core. The fluorescence transients of 1(8t) and 1(3t5c)
(shown in the bottom panel of Figure 10) fit well to single
PDI core of 1 can be used as a sensitive fluorescent probe. Here,
we demonstrate that the photoisomerization of the AB groups
switches significantly the efficiency of intramolecular energy
transfer from AB to PDI. Although photoswitching of intramo-
73ꢀ75
lecular energy transfer has previously been reported for dyads,
1
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Table 2. Parameter of the Single Exponential Fits [according
to y = A exp(ꢀx/t )] to the Decay Transients Shown in the
1
1
Lower Panel of Figure 10
A
1
1
t /ns
1
(8t)
1.0336 ( 0.0005
0.9433 ( 0.0012
5.327 ( 0.002
4.674 ( 0.005
1(3t5c)
exponential decays, as shown in Table 2, showing a slightly shorter
fluorescence lifetime of the PDI chromophore in 1 (3t5c).
However, the observed lifetime difference cannot account for
the decrease of the PLQE of 1(3t5c). In fact, the fluorescence
quenching must occur in the first 1 ns after excitation, i.e., much
faster than the time resolution of our experiment, indicating that
a rapid deactivation process quenches a considerable fraction of
the PDI excited states. Upon excitation at 365 nm the PLQE of
Figure 11. Transient absorption spectra of 1(8t) excited at 570 nm
(upper panel) and 365 nm (lower panel). After excitation of the
1
(8t) is only one-third that of the PLQE at 550 nm excitation,
azobenzene (at 365 nm), an intense and broad photoinduced absorption
(PA) of the azobenzene group covers all other signals. However, the
induced absorption decays much faster than the excited states of the PDI
and thus the PDI bleach and PA become visible after about 100 ps.
indicating that the intramolecular energy transfer from the
azobenzene groups to the PDI core is incomplete. This appears
reasonable because some of the absorbed photons drive the trans
to cis photoisomerization reaction and thus will not create
excited states that can be transferred to the PDI core; however,
there must be an additional deactivation process for the excited
states of the AB units to explain the moderate quantum efficien-
cies, as we will show below by ultrafast transient absorption
spectroscopy.
Applying the same conditions to 1(3t5c) shows a PLQE of
about 37%, similar to the PLQE observed upon direct excitation
of the PDI chromophore of 1(3t5c). We exclude direct excitation
of the PDI at 365 nm, since the absorbance of the PDI is
negligible at this wavelength in comparison to the absorbance
of the AB units. Thus, within the experimental error of our PLQE
measurement, the efficiencies of 1 (3t5c) are similar, irrespective
of direct excitation of the PDI core or excitation of the AB units
and subsequent energy transfer to the PDI core. This in turn
implies that in 1(3t5c) the energy transfer from the azobenzene
units to the PDI core is very efficient. The higher fluorescence
efficiency of 1(3t5c) upon excitation at 365 nm can also be
observed by a direct comparison of intensity-calibrated fluores-
cence spectra, which show stronger emission from 1(3t5c) than
absorption (PA) of excited singlet states of PDI chromophores
can be observed. In comparison to the spectra obtained after
excitation at 570 nm, the bottom panel of Figure 11 shows the
TA spectra of 1(8t) at different delay times after excitation at
365 nm. Here, a broad and intense photoinduced absorption of
the azobenzene groups clearly dominates the spectra at early
times. However, after about 100 ps the broad PA signal of the
azobenzene groups has vanished and the typical TA features of
the PDI chromophore can be observed in the TA spectra
(compare also upper panel of Figure 11). A singular value
decomposition (SVD) analysis of the TA data set indicated the
presence of two main processes that dominate the photophysics.
First, some excitons on the AB units undergo a rapid energy
transfer to the PDI core, leaving a fraction of the previous
excitations on the PDI, which subsequently decay with the same
lifetime of several nanoseconds observed for the excitation at
570 nm. The presence of an energy transfer process is also
supported by the PL and PLQE measurements shown above that
demonstrate emission from the PDI chromophore upon excita-
tion of the dendrimer at 365 nm, although the absorbance of the
PDI chromophores with respect to the AB units is negligible at
this wavelength. Second, a rapid deactivation process of a fraction
of the excited states of the azobenzene moieties within a few tens
of picoseconds occurs. The latter is also supported by the
dynamics of the TA signal in the region of the PDI photo-
induced absorption, which shows a rapid initial drop of the
signal due to fast deactivation of the excited states on the
azobenzene groups (see Supporting Information Figure 7).
Hence, it is not possible to entirely disentangle the energy
transfer process from the AB units to the PDI core, since the
intrinsic decay occurs on a similar time scale and the features
of the PDI chromophores are entirely superimposed by the
comparably strong PA of the AB units, which complicates the
data analysis. However, the TA experiments clearly demon-
strate that the energy transfer to the PDI and intrinsic decay of
the excited states on the AB units occur within a few tens of
picoseconds, which is rapid enough to create a considerable
amount of excited states on the PDI core and explains the
substantial quantum efficiency of the PDI even for the all-trans
dendrimer after excitation at 365 nm.
1
(8t) (Supporting Information Figure 5), unlike that seen for
direct excitation of the PDI core at 570 nm. Hence, our results
show that we could successfully gain control over the efficiency of
intramolecular energy transfer from AB to PDI in 1 by simple
photoswitching of AB. This opens up several possibilities to
design novel donorꢀacceptor-type dendrimers with photo-
switchable energy transfer properties having potential applica-
tions, for instance, as photon-harvesting molecules for photon
energy conversion.
In order to get a better insight into the excited state dynamics
of 1(8t) upon excitation at 365 and 550 nm, we performed
ultrafast transient absorption (TA) experiments on the dendri-
mer in solution. The upper panel of Figure 11 shows the TA
spectra of the trans-isomer at increasing delay times after
excitation of the PDI core at 570 nm.
The spectra exhibit the TA features typically seen for PDI
chromophores. Between 550 and 650 nm a combination of
ground state bleaching and stimulated emission can be found. An
isosbestic point at 650 nm points to the presence of a single
excited species, i.e., singlet excited states of the PDI chromophore.
At wavelength longer than 650 nm the typical photoinduced
1
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Journal of the American Chemical Society
.4. Guest Uptake and Photoswitchable Encapsulation
ARTICLE
2
and Release. Prior to a study on active guest encapsulation, the
general ability of dendrimer 1 to act as a host for guest molecules
was investigated. Hostꢀguest studies are often performed by
using fluorescent guest molecules and detecting changes in their
fluorescence output signal as an indicator for changes in their
chemical environment. However, the dendritic host 1 already
contains two different types of chromophores (PDI and AB),
rendering a study by fluorescence detection inadequate. Instead,
a simple, nonfluorescent molecule, p-nitrophenol (p-NP), was
chosen as the guest for uptake studies by means of NMR and
UVꢀvis spectroscopy.
1
Figure 12. Details of H NMR spectra (300 MHz, CD
2
Cl
2
,7295 K) of
7
titration experiment upon increasing the number of guests.
p-Nitrophenol fulfills some important requirements regarding
both guest uptake and later encapsulation studies:
1
(
i) p-NP exhibits H NMR signals with distinct chemical
shifts compared to host 1 (facile detection of potential
signal changes in the NMR spectra of hostꢀguest
mixtures).
(
(
ii) p-NP bears one phenolic proton (potential formation of
hydrogen bonds to pyridin moieties of the host).
iii) p-NP is soluble in methanol, while the host 1 is insoluble
and precipitates. This solubility difference enables a facile
separation of host and guest.
The guest uptake experiment was performed directly in a
ꢀ
3
NMR tube containing a 10 M solution of 1 in CD Cl . Upon
2
2
2 2
Figure 13. Absorption spectra of p-nitrophenol in CH Cl at 298 K: red
curve, in absence of host 1; dashed black curve, in the presence of host 1.
adding 2 equiv of p-NP, the signal ascribed for the phenolic
proton of p-NP disappeared and the signal of H significantly
1
shifted upfield (see Supporting Information Figure 6).
Similarly, signals assigned to protons of the interior cavities of
guest. The change is probably caused by the transition of guest
molecules from the more polar solution to the less polar environ-
ment of dendritic cavities.
1
(Hazo, H , and HPDI) shifted upfield while other proton
G1
signals of 1 (e.g., peripheral protons) did not, indicating that the
After demonstrating the ability of host 1 to take up p-NP
guests, we wondered whether it would be possible to perma-
nently encapsulate such guests into internal cavities of 1 by
switching from the “open” to the “closed” form. Therefore, a
solution mixture (3 mL) of the dendritic host 1 (0.25M, 1 equiv)
and guest molecules p-NP (5M, 20 equiv) was irradiated at
365 nm to induce the “closing” of 1 by trans-to-cis isomerization
of its AB moieties (Figure 14A,B). By doing so, the fraction of
guest molecules that resided in the interior cavities of 1 before
switching should now be encapsulated therein. This experiment
was repeated three times. A control experiment was performed in
parallel, in which the solution was not irradiated at 365 nm and
thus no encapsulation of guest molecules should have occurred.
Both solutions were concentrated by evaporation of three-
quarters of their solvent. The concentrated solutions were then
added dropwise into methanol. Due to the different solubility of
host and guest in methanol, the host 1 precipitated completely,
while guest molecules remained completely dissolved. After
separation of the host 1 from the solution by centrifuge and
filtration, the precipitate was thoroughly washed twice with fresh
methanol in order to remove remaining guest molecules that
majority of guests molecules resides in the dendrimer cavities
(see Supporting Information Figure 4). Surprisingly, the phe-
nolic proton of p-NP did not show significant hydrogen bonding
to the pyridyl functions of the host, despite its relatively high
acidity. Only a large amount of guest (more than 10 equiv)
induced a slight upfield shift of H along with the emergence of
py
two new Hpy peaks (Figure 12). Probably, the N atoms in the
ortho-positions exhibit only a limited accessibility toward guests.
In order to better enhance guest uptake by hydrogen bonds, the
N atom could in the future be placed in the meta- or para-
position. However, despite of negligible H-bond interaction
between host 1 and guest p-NP, the guest was still preferably
directed toward interior cavities of the host.
Hostꢀguest interactions were also investigated by UVꢀvis
spectroscopy. Figure 13 shows the absorption spectrum of
the free guest p-NP and of the guest in the presence of host 1
(
guest/host = 10/1). Due to the overlapping absorption spectra
of host and guest species, the spectrum of the guest in the
presence of host 1 was obtained by subtraction of the spectrum of
1
from that of the mixture.
As demonstrated in Figure 13, the guest absorption band
0
might have been superficially adsorbed (Figure 14C,C ). After
exhibits a hypsochromic shift in the presence of only 0.1 equiv of
host 1 as compared to the absorption band in the absence of host.
The shift indicates a change in the chemical environment of the
drying, the precipitated host 1 was dissolved in deuterated
1
methylene chloride and measured by H NMR spectroscopy
0
(Figure 14,D,D ).
1
1201
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Journal of the American Chemical Society
ARTICLE
change in molecular size upon photoisomerization (66% decrease
in hydrodynamic volume upon trans-to-cis isomerization, as
confirmed by FCS) is unprecedented as compared to earlier
2
2
AB-functionalized dendrimers.
The fluorescent PDI core allows for a tracking of the dendritic
host by fluorescence techniques, such as confocal microscopy or
stimulated emission depletion (STED) microscopy. Addition-
ally, it can be used as a sensitive optical probe of intramolecular
energy transfer processes. In fact, we could not only show
intramolecular energy transfer within the dendrimer, as already
reported for other donorꢀacceptor-type dendrimers, but we
could also demonstrate that the efficiency of the intramolecular
energy transfer is greatly enhanced in 1(3t5c) compared to 1(8t).
Thus, dendrimer 1 is to the best of our knowledge the first
example for efficient photoswitching of intramolecular energy
transfer in a dendritic structure using AB as donor and PDI
as acceptor.
Figure 14. Encapsulation experiment (green arrows) and control
experiment (blue arrows): (A) solution of host and guest in methylene
chloride, (B) photoinduced “closing” of the host, (C) separation and
washing of host with methanol, (D) detection of potential guests via
The presence of o-pyridyl functions only had a minor con-
tribution to the direction of guest molecules into dendritic
cavities. Nevertheless, sufficient uptake of p-NP guests was
confirmed by NMR and UVꢀvis spectroscopy.
1
H NMR.
Finally, we have demonstrated that the photoswitchability
of the host can be utilized actively to encapsulate guest
molecules into its interior cavities. This novel, light-driven
encapsulation mechanism has important implications for the
design of new drug delivery systems. It could prevent pre-
mature leaching of drugs from their hosts without the require-
ment of covalent linking and thus enable the delivery of
unmodified and active drugs. The number of encapsulated
guests might be further increased in the future by way of fine
adjustments of the host design, including the size of its interior
cavities and their functionalization. Hostꢀguest interactions
could be further enhanced by incorporating different groups
(such as p-pyridyl or pyridinone) in the place of o-pyridyl
functions. Since applications in a biologic environment re-
quire both water solubility and biocompatibility, our current
work is focused on changing the solubility and membrane
permeability properties of our dendritic host via suitable
functionalization of its periphery.
1
Figure 15. H NMR spectrum of the complex hostꢀguest in the
encapsulation experiment (blue line) and in the control experiment
red line). Two guests per host 1 were observed only in the encapsula-
tion experiment.
(
As expected, not even trace amounts of guest molecules could
be detected in any control experiment, where the dendritic host 1
remained in the “open” conformation all the time.
78
By contrast, an average of about 2 equiv of guest molecules
per dendrimer was detected in the experiments where the
dendritic host 1 had previously been switched to the “closed”
conformation (Figure 15). The guest molecules could be re-
leased either by irradiation of the “closed” host with blue light or
by the slow thermal process of cis-to-trans isomerization. These
results clearly demonstrate that guest molecules can indeed be
entrapped into suitably designed hosts via a photoswitched
mechanism, as proposed in the Introduction.
’
ASSOCIATED CONTENT
S
Supporting Information. Experimental details including
b
procedures for preparation and full characterization of com-
pounds 1, 3, 4ꢀ6, 8, 9, 12, and 15ꢀ19 and figures as noted in the
text. This material is available free of charge via the Internet at
http://pubs.acs.org.
’
AUTHOR INFORMATION
Corresponding Author
muellen@mpip-mainz.mpg.de
3
. CONCLUSION
We have demonstrated the successful synthesis of a fluores-
cent dendritic host with photoswitchable properties. Our design
utilizes the unique rigidity of the PPD scaffold for a site-specific
placement of three different types of function (PDI, pyridine, and
azobenzene).
The employment of eight azobenzene moieties as hinges in
defined positions of the rigid scaffold enables the photoswitch-
ability of (i) molecular size, (ii) intramolecular energy transfer,
and (iii) guest encapsulation and release. The magnitude of
’
ACKNOWLEDGMENT
We thank Prof. Dr. Martin Baumgarten, Khalid Chiad, Oliver
Dumele, and Qui Su for their support; Chen Li for his fruitful
discussions, Dr. Kaloian Koynov for FCS measurement, Sandra
Seywald for GPC measurements; Manfred Wagner and Petra
Kindervater for NMR measurements; and Stephan T €u rk for
MALDI-TOF measurements.
1
1202
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Journal of the American Chemical Society
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69) First, the initial solution of dendrimer 1 (without any
ARTICLE
(
irradiation) was exposed to 450 nm light for 2 min, so that the solution
can reach the photostationary state at 450 nm (PSS 450 nm, solid red
line shown in Figure 4). At this state, the absorbance value at 370 nm was
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GPC column before being detected (for more details, see Supporting
Information Figure 9)
ꢀ
4
(
72) A 5.4 ꢁ 10 M solution of 1 in CD Cl was irradiated at
2
2
3
65 nm for 60 min. The longer irradiation time compared to previous
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77) To a 5.4 ꢁ 10 M solution of 1 in CD Cl were added precise
2
2
2 2
amounts of guest molecules (0.1 M solution in CD Cl ) successively.
1
After each addition, the H NMR spectrum of the mixture was recorded.
Due to the relatively high concentration of guest solution, the volume
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(
78) A value of two guest molecules per dendrimer was obtained
when a mixture (3 mL) of the dendritic host 1 (0.25 M, 1 equiv) and
guest molecules p-NP (5 M, 20 equiv) was used. When using less than
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1
1204
dx.doi.org/10.1021/ja2022398 |J. Am. Chem. Soc. 2011, 133, 11194–11204