Light-Triggered Transformation of Molecular Baskets into Organic Nanoparticles

Article abstract of DOI:10.1002/chem.201803693

Discovering novel and functional photoresponsive materials is of interest for improving controlled release of molecules and scavenging toxic compounds for cleaning our environment or designing chemosensors. In this study, we report on the photoinduced decarboxylation of basket 1^6?, containing three glutamic acids at its rim. This concave compound is, in an aqueous environment (30 mm phosphate buffer at pH 7.0), monomeric (¹H NMR DOSY, DLS) with glutamic acid residues randomly oriented about its rim (¹H NMR and MM-OPLS3). The irradiation (300 nm) of 1^6? leads to the exclusive removal of its α-carboxylates to give amphiphilic 2^3? possessing γ-carboxylates. The photochemical transformation is a consecutive reaction with mono- and bis-decarboxylated products observed with ¹H NMR spectroscopy and ESI mass spectrometry. Amphiphilic 2^3? is a preorganized molecule (MM-OPLS3) that, in water, aggregates into organic nanoparticles (ca. 50–200 nm in diameter; DLS, TEM and cryo-TEM) having a critical aggregation concentration of 12 μm (UV/Vis). As the transition of monomeric 1^6? into nanoparticulate 2^3? is triggered with light, we reasoned that stimuli-responsive formation of the soft material lends itself to nanotechnology applications such as controlled release or scavenging of targeted compounds.

Full text of DOI:10.1002/chem.201803693

DOI: 10.1002/chem.201803693
Full Paper
&
Photoresponsive Materials |Hot Paper|
Light-Triggered Transformation of Molecular Baskets into Organic
Nanoparticles
+ [a]
+ [a]
[a]
[a]
[b]
´
Sarah E. Border , Radoslav Z. Pavlovic , Lei Zhiquan, Michael J. Gunther, Han Wang,
[b]
[a]
´
Honggang Cui, and Jovica D. Badjic*
Abstract: Discovering novel and functional photoresponsive
materials is of interest for improving controlled release of
molecules and scavenging toxic compounds for cleaning our
environment or designing chemosensors. In this study, we
report on the photoinduced decarboxylation of basket 16À,
containing three glutamic acids at its rim. This concave com-
pound is, in an aqueous environment (30 mm phosphate
buffer at pH 7.0), monomeric (1H NMR DOSY, DLS) with glu-
tamic acid residues randomly oriented about its rim (1H NMR
and MM-OPLS3). The irradiation (300 nm) of 16À leads to the
exclusive removal of its a-carboxylates to give amphiphilic
23À possessing g-carboxylates. The photochemical transfor-
mation is a consecutive reaction with mono- and bis-decar-
1
boxylated products observed with H NMR spectroscopy and
ESI mass spectrometry. Amphiphilic 23À is a preorganized
molecule (MM-OPLS3) that, in water, aggregates into organic
nanoparticles (ca. 50–200 nm in diameter; DLS, TEM and
cryo-TEM) having a critical aggregation concentration of
12 mm (UV/Vis). As the transition of monomeric 16À into
nanoparticulate 23À is triggered with light, we reasoned that
stimuli-responsive formation of the soft material lends itself
to nanotechnology applications such as controlled release or
scavenging of targeted compounds.
Introduction
cy by exposing affected areas to the stimulus and concurrently
tune the pharmacokinetics via modulation of the exposure
time/intensity.[12] So far, isomerization of azobenzenes,
dithienylethene and spyropirans as well as degradation of o-ni-
trobenzyl derivatives constitutes prevalent photochemical
strategies[13] for manipulating chemical/physical characteristics
of soft matter with light.[14] It follows that developing novel
photo-responsive[15] or photo-caging[16] methods could be ben-
eficial for: (a) improving compatibility, stability and per-
formance of materials in aqueous environments and (b) per-
mitting utilization of parallel input signals for activation of “or-
thogonal” switches and building multifunctional structures. In
this vein, we recently discovered[17] that molecular baskets with
a-amino acids at their rim, and nerve-agent simulants residing
in their cavity, undergo photo-induced decarboxylation[18] and
precipitation, amounting to a method for the removal of toxic
warfare agents from water. Will the irradiation of deeper-cavity
16À (Figure 1), containing three glutamic acids at its rim, elicit
the elimination of a- and/or g-carboxylates to give fully or
partly decarboxylated baskets in addition to other cyclic[19] and
radical-mediated products?[20]
The assembly of small molecules or functional polymers into
nanostructured materials[1] constitutes a powerful methodolo-
gy for bottom-up construction of nanotubes, gels, vesicles, mi-
celles, nanofibers and other hierarchical structures.[1b,2] In par-
ticular, the responsive characteristics[3] of such soft matter have
been of a considerable interest for application in the areas of
tissue engineering,[4] drug delivery,[5] systems chemistry[6] and
sensing.[7] Accordingly, one could use light, ultrasound, chemi-
cal, magnetic or redox input to trigger a conformational
change or rupture of weak bonds within the material’s build-
ing blocks to switch its packing and therefore physical and
chemical characteristics.[3b,8] The photochemical stimulus[9] pro-
vides precise spatial and temporal control over the switching
process,[10] which is of particular value for the smart delivery of
drugs.[8a,11] That is to say, one can reduce undesired side ef-
fects, improve selectivity and therefore optimize drug’s poten-
[a] S. E. Border,+ R. Z. Pavlovic, Dr. L. Zhiquan, M. J. Gunther, Prof. J. D. Badjic
Department of Chemistry & Biochemistry, The Ohio State University
100 West 18th Avenue, 43210 Columbus, Ohio (USA)
E-mail: badjic.1@osu.edu
+
´
´
In this study, we found that C3 symmetric and hexaanionic
16À stays monomeric in water at pH 7 (Figure 1). When
prompted with light stimulus, however, 16À undergoes a con-
secutive loss of three a-carboxylates to give 23À (Scheme 1).[17]
Following, preorganized and amphiphilic 23À (comprising a hy-
drophobic cage and three aliphatic chains conjugated to polar
carboxylates) assembles into spherical nanoparticles as, we
posit, concave hosts populate the space of such nanosized ob-
jects.[2f] With light stimulus triggering the formation of unique
[b] H. Wang, Prof. H. Cui
Department of Chemical and Biomolecular Engineering
The Johns Hopkins University, Maryland Hall 221
3400 North Charles Street, 21218 Baltimore, Maryland (USA)
[+] These authors contributed equally to this work.
Supporting information and the ORCID identification number(s) for the
author(s) of this article can be found under:
https://doi.org/10.1002/chem.201803693.
Chem. Eur. J. 2018, 24, 1 – 8
1
ꢀ 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Full Paper
Figure 1. (A) The condensation of (S)-Glu and tris-anhydride 3 gives basket 1 in 93% yield. (B) 1H-NMR spectra (700 MHz, 298 K) of basket 16À (top, 3.0 mm)
and model compound 42À (bottom, 3.0 mm) in 30 mm phosphate buffer at pH 7.0.
1
Scheme 1. (A) The irradiation (300 nm, Rayonet) of 3.0 mm solution of 52À (10 mm phosphate buffer, pH 7.0) was monitored with H NMR spectroscopy (Fig-
ure S24) to reveal the exclusive formation of 6. A speculative and electron-pushing mechanism of the photoinduced cyclization is shown.[19] (B) The photo-
chemical conversion of 16À into 23À occurs in a stepwise fashion via partly decarboxylated 25À ad 24À. (C) The condensation of 3a and g-aminobutyric acid
gives basket 2 in 55% yield. Similarly, the condensation of 3a and propyl amine gives 7 in 64% yield.
&
&
Chem. Eur. J. 2018, 24, 1 – 8
www.chemeurj.org
2
ꢀ 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Full Paper
nanosized structures,[21] composed of concave hosts, there
exists an opportunity for creating novel and useful stimuli-re-
sponsive materials.[22]
ular, one a-carboxylate group in 16À prefers the inner basket’s
side (Figure 2A) with neighboring g-carboxylate residing in
bulk solvent. Another glutamic acid, however, positions its g-
carboxylate on the inner side of the host (Figure 2A) with HA/A’
and HB/B’ methylene nuclei on top of the basket’s cavity: the
magnetic shielding of these protons is likely contributing to
the observed and upfield NMR chemical shifts (Figure 2B)
thereby providing support to our hypothesis.
Results and Discussion
Basket 1 was obtained by the condensation of tris-anhydride 3
1
and (S)-glutamic acid in dimethyl sulfoxide (Figure 1A). H NMR
A hundred-fold dilution of an aqueous solution of 16À
(5.1 mm, Figure S8) had no effect on the line shape of its
spectrum (700 MHz, 298 K) of 16À showed a set of signals cor-
responding to a C3 symmetric compound (Figure 1B). We used
1
narrow H NMR resonances. Moreover, the experimentally mea-
1
1H–1H COSY and NOESY along with H–13C HSQC spectroscopic
sured hydrodynamic radius rH =8.3 ꢁ of 16À (D=2.9ꢂ
10À10 m2 sÀ1; Figure S9) was consistent with the computed 11 ꢁ
(Figure 2C) of a single molecule of 16À. Additionally, model
compound 42À was found to undergo translational diffusion at
a faster rate (D=4.9ꢂ10À10 m2 sÀ1, Figure S10) than 16À, corre-
sponding to rH =4.9 ꢁ and close to its estimated radius of
6.0 ꢁ (Figure 2C). DOSY NMR of 16À and 42À revealed two sets
of signals with each compound moving as predominantly free
species (Figure 2C); the results of dynamic light scattering
(DLS, Figure S11) and electrospray ionization mass spectrome-
try analyses (ESI-MS, Figure S12) of 16À were in line with the
host being monomeric in water. The solution behavior of 16À is
thus similar to baskets conjugated to hydrophobic amino
acids[23] in spite of its nonpolar cage being bordered with six,
instead of three,[23] negatively charged carboxylates. We pre-
sume that the conformational dynamics of glutamic acid moi-
eties along with their different orientations about the rim of
16À (as computed with molecular mechanics, Figure 2A) is con-
tributing to the poor preorganization of this host to frustrate
its aggregation in water.[26]
correlations (Figures S1–S7) to assign all of the basket’s reso-
nances. Notably, diastereotopic HA/A’ and HB/B’ protons from 16À
exhibit a greater magnetic shielding than the corresponding
nuclei in model compound 42À (Figure 1B).[23] As HA/A’ and HB/B’
could reside on top of the host’s cavity (Figure 2A), we sur-
mised that the unique microenvironment of this concave
region of space[24] could have an effect on the magnetic char-
acteristics of these spins. On the contrary, two sides about the
flat phthalimide 42À (Figure 1B) are, for HA/A’ and HB/B’ almost
equivalent and similar to the outer side of 16À. To examine the
above hypothesis and gain further insight into the conforma-
tional characteristics of 16À, we completed the Monte-Carlo
conformational search of this molecule (Maestro, OPLS3)[25] in
implicit water solvent. First, (a)CÀH groups are for the thirty
most stable conformers of 16À (within 2.93 kcalmolÀ1 of their
relative steric energies, Figure 2A) eclipsed with the adjacent
NÀC(=O) bonds[23] (Figure 2B) so that a-carboxylates become
situated on the inner or the outer side of the basket. In partic-
After the absorption of 300 nm light, the phthalimide frag-
ment of N-phthaloyl-a-amino acids[27] turns into transient but
strong oxidizing agents capable of “pulling” an electron from
a-carboxylate to instigate decarboxylation (Scheme 1).[19] In the
case of baskets functionalized with hydrophobic a-amino
acids,[17] we found that the photo-induced loss of CO2 would
render these hosts insoluble in water to prompt their precipita-
tion. With six carboxylates within 16À, however, we wondered
if a light stimulus would trigger their removal[20a] to give bas-
kets possessing distinct recognition characteristics and/or solu-
bility (Scheme 1B). In fact, when N-phthaloyl-glutamic acid 52À
(10 mm phosphate buffer, pH 7.0) was exposed to 300 nm light
(Scheme 1A) there followed the exclusive formation of cyclized
product 6 (Figure S13).[20a] On the basis of the literature,[19] we
3
speculate that the formation of long-lived pp* triplet state of
the phthalimide chromophore from 52À triggers the removal of
a and g carboxylates to give diradical intermediate which then
cyclizes into racemic 6 (the Norrish–Yang reaction).
Irradiation (300 nm, Rayonet) of an aqueous solution of 16À
was, at 298 K, monitored with 1H NMR spectroscopy (Fig-
ure 3A). The signals corresponding to 16À gradually disap-
peared over 180 minutes with the concomitant emergence of
a set of poorly resolved and broadened resonances. Since
there was no precipitate, to indicate the formation of water in-
soluble 7 (Scheme 1B), we suspected that partial decarboxyl-
ation(s) of 16À and/or other radical-mediated reactions[20b]
Figure 2. (A) Thirty conformers of 16À, with relative steric energy within
2.93 kcalmolÀ1, were obtained from the Monte-Carlo conformational search
(OPLS3, Maestro; Schrodinger) in implicit water. (B) The Newman projections
of one glutamic acid moiety from 16À with its stereogenic carbon at front.
(C) DOSY NMR (600 MHz, 298 K) of 1.0 mm of 16À and 1.0 mm 42À in 30 mm
phosphate buffer at pH 7.0; note that two DOSY experiments were run sepa-
rately. (Right) van der Waals surface of 16À and 42À, each with their diameter
estimated using Spartan Software.
Chem. Eur. J. 2018, 24, 1 – 8
www.chemeurj.org
3
ꢀ 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Full Paper
1
Figure 3. (A) Irradiation (300 nm, Rayonet) of basket 16À (2.1 mm) dissolved in 30.0 mm phosphate buffer at pH 7.0 was monitored with H NMR spectroscopy
(600 MHz, 298 K); in the experiment, pH of the solution changed from 7.0 to 7.2. (B) 1H NMR spectra (700 MHz, 298 K) of 2 in CD3SOCD3 with this molecule ob-
tained from photochemical (top) and condensation (bottom) experiments. (C) 1H NMR spectra (600 MHz, 298 K; CD3SOCD3) of 1 (blue, bottom) and 2 (red,
top) along with the reaction mixture (middle) obtained after irradiation (300 nm, Rayonet) of 16À (2.1 mm) in 30 mm phosphate buffer (20% D2O) at pH 7.0
for 40 minutes. See Figure S19 for additional information. (D) ESI-MS of a sample obtained by Irradiation (300 nm, Rayonet) of 16À (2.1 mm) in 30 mm phos-
phate buffer for 40 minutes followed by the addition of 2m HCl with the resulting precipitate being dissolved in CH2Cl2/CH3OH.
1
could have taken place. An ill-defined H NMR spectrum ob-
tained after 180 minutes of the light exposure (Figure 3A)
could therefore denote: (a) a mixture of products and/or
(b) one major product undergoing aggregation with/without a
slow exchange of its conformers on the NMR time scale. To ex-
amine the matter more closely, we subjected 16À to irradiation
until its 1H NMR signals disappeared (c.a. 180 min) and then
(Scheme 1).[17] In this regard, the available spectroscopic results
from the photochemical transformation in Figure 3A were diffi-
cult to elucidate for identifying resonances from partly decar-
boxylated baskets. Accordingly, we terminated the reaction at
approximately 50% conversion (Figure S19), precipitated all of
the products with 2m HCl and dissolved the precipitate in
CD3SOCD3; note that in this experiment, no detectable organ-
1
1
precipitated all organics using 2m HCl; H NMR spectroscopy
ics remained in the water layer. H NMR spectrum of the pre-
showed no presence of organics in the remaining aqueous
cipitate showed signals corresponding to 1 and 2 yet there
were also additional resonances to, perhaps, suggest the pres-
ence of 24À and 25À intermediates (Figure 3C). Indeed, ESI-MS
analysis of the sample verified the formation of singly- and
doubly decarboxylated basket 1 (Figure 3D). The results are in
support of a mechanistic scenario in which the light triggers a
successive elimination of CO2 molecules from 16À to, via 25À
and 24À, give 23À (Scheme 1). The rates by which these elimina-
tions occur are likely different than in the case of hydrophobic
a-amino acids conjugated to the basket’s framework since
these hosts did not give detectable quantities (NMR) of partly
decarboxylated intermediates.[17]
1
layer (Figure S14). H NMR spectrum of the solid dissolved in
CD3SOCD3 (Figure 3B), however, showed a set of resonances
corresponding to C3 symmetric 2 lacking a- but still possessing
g-carboxylic groups! To confirm our structural assignment, we
prepared 2 by condensation of tris-acid 3a and g-aminobutyric
1
acid in acetic acid (Scheme 1B). Importantly, H NMR spectra of
“photochemical” and “synthetic” samples (Figure 3B) were
identical to corroborate the sole formation of 2 with light; for
complete characterization of 2 and 7, see Figures S15–18. To
1
sum up, we deduced that the ill-defined H NMR spectrum in
Figure 3A resulted from the aggregation of 23À.[26]
At this point, we were eager to examine the involvement of
24À and 25À intermediates in the photochemical conversion
As the light stimulus triggers decarboxylation of monomeric
16À into 23À, we wondered: does the irradiation launch the for-
&
&
Chem. Eur. J. 2018, 24, 1 – 8
www.chemeurj.org
4
ꢀ 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Full Paper
Figure 4. (A) Overlaid conformers of 23À were generated with the Monte-Carlo conformational search (OPLS3, Maestro; Schrodinger). (B/C) Plots of absorbance
(229 and 245 nm) as a function of concentration of standard solutions of 16À and 23À (30 mm phosphate buffer, pH 7.0). Each data set was subjected to a non-
linear least square analysis and fit to a linear function using Sigma Plot (R2 >0.98). (D) Size distribution of 1.0 mm solution of 23À (phosphate buffer, pH 7.0) ex-
amined with dynamic light scattering at 298.0 K. (E/F) Conventional TEM and cryo-TEM images of 1.0 mm 23À (10 mm phosphate buffer, pH 7.0). For conven-
tional TEM imaging, the sample was deposited on a copper grid and subsequently stained with uranyl acetate aqueous solution; for additional microscopy
images, see Figures S23 and S24.
mation followed by assembly of amphiphilic 23À into a distinct,
perhaps, nanostructured material?[2e] After all, the observed re-
gioselective removal of a- but not g-carboxylates from 23À
could, in part, result from the reduced conformational dynam-
ics of “aligned” hosts. That is to say, extended and confined
GABA chains within assembled molecules 23À are likely to
impede g-carboxylates from reaching the bottom portion of
each basket thereby reducing the rate of intramolecular elec-
tron transfer preceding the removal of the appropriate CO2
(Scheme 1A).[19]
To study the conformational characteristics of 23À, we ran
the Monte-Carlo conformational search (OPLS3) in implicit
water solvent to find numerous conformers of which the most
stable 154 (within 1.4 kcalmolÀ1 of steric energy) are shown in
Figure 4A.
phthalimide chromophores.[30] Additionally, the nanosized ag-
gregates should scatter the incident light beam (Tyndall effect)
and therefore alter its transmission intensity. To sum up, the
onset of the aggregation of 23À (CAC) may be possible to dis-
cern as a deflection in the linear behavior described with the
Beer–Lambert law.[31] From UV/Vis spectra of standard solutions
of 16À and 23À (Figures S20 and S21), we plotted a change in
the absorbance as a function of the concentration (Figure 4B/
C); As expected, the Beer–Lambert law holds for 16À in the
entire range of the examined concentrations to corroborate its
monomeric state (Figure 4B). However, two linear curves were
distinguished for 23À converging at around 12 mm concentra-
tion to suggest a two-state phase transition;[29] note that
1H NMR spectrum of 23À would also sharpen at ꢀ10 mm con-
centrations (Figure S22). Accordingly, we conclude that CAC of
23À, at which the host effectively changes from its monomeric
to aggregated state, is 12 mm. Dynamic light scattering (DLS)
measurements of 1.0 mm solution of 23À showed a single peak
centered at 180 nm (Figure 4D) to indicate the formation of
particles having hydrodynamic diameter DH =20(Æ25) nm and
a narrow distribution of sizes (PDI=0.25). Transmission elec-
tronic micrographs of 0.1 mm solution of 23À revealed the for-
mation of circular objects with a dark boundary resulting from
the negative stain (Figure 4E).[32] The diameter of these struc-
tures is circa 90 nm and somewhat smaller than the size of par-
ticles detected with DLS. At last, cryo-TEM imaging of 23À (Fig-
The host has a shape of truncated cone with distinct hydro-
phobic and hydrophilic zones: three butyric acid chains cluster
their carboxylates at the northern and outer side of the basket
to cast a deep hydrophobic pocket. Clearly, amphiphilic 23À is
preorganized and shaped[2e] to form nanostructured materi-
als.[26,28]
To examine the mode of aggregation of 23À, we decided to
begin with probing the potential phase transition of the mate-
rial as distinguished with critical aggregation concentration
(CAC).[29] In the aggregated form, molecules of 23À should form
close contacts that may perturb the electronic state of their
Chem. Eur. J. 2018, 24, 1 – 8
www.chemeurj.org
5
ꢀ 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Full Paper
Mater. 2014, 26, 507; e) T. Shimizu, M. Masuda, H. Minamikawa, Chem.
Rev. 2005, 105, 1401; f) L. Zhang, A. Eisenberg, Science 1995, 268, 1728.
[3] a) X. Yan, F. Wang, B. Zheng, F. Huang, Chem. Soc. Rev. 2012, 41, 6042;
b) S. Rieth, C. Baddeley, J. D. Badjic, Soft Matter 2007, 3, 137.
[4] M. Goldberg, R. Langer, X. Jia, J. Biomater. Sci. Polym. Ed. 2007, 18, 241.
[5] E. Cabane, V. Malinova, S. Menon, C. G. Palivan, W. Meier, Soft Matter
2011, 7, 9167.
[6] Y. Elani, R. V. Law, O. Ces, Nat. Commun. 2014, 5, 5305.
[7] C. Ren, J. Zhang, M. Chen, Z. Yang, Chem. Soc. Rev. 2014, 43, 7257.
[8] a) A. Abdul Karim, Q. Dou, Z. Li, X. J. Loh, Chem. Asian J. 2016, 11, 1300;
b) Z. Dai, H. M. Leung, P. K. Lo, Small 2017, 13, 1602881; c) A. C. Stuart
Martien, T. S. Huck Wilhelm, J. Genzer, M. Muller, C. Ober, M. Stamm, B.
Sukhorukov Gleb, I. Szleifer, V. Tsukruk Vladimir, M. Urban, F. Winnik, S.
Zauscher, I. Luzinov, S. Minko, Nat. Mater. 2010, 9, 101; d) J. R. Kumpfer,
J. Jin, S. J. Rowan, J. Mater. Chem. 2010, 20, 145; e) R. Lehner, X. Wang,
M. Wolf, P. Hunziker, J. Controlled Release 2012, 161, 307; f) H. Che,
J. C. M. van Hest, J. Mater. Chem. B 2016, 4, 4632.
[9] M.-M. Russew, S. Hecht, Adv. Mater. 2010, 22, 3348.
[10] a) E. R. Draper, D. J. Adams, Chem. Commun. 2016, 52, 8196; b) N. Basi-
lio, L. Garcia-Rio, Curr. Opin. Colloid Interface Sci. 2017, 32, 29.
[11] a) S.-M. Lee, S. T. Nguyen, Macromolecules 2013, 46, 9169; b) M.-H. Li, P.
Keller, Soft Matter 2009, 5, 927; c) S. Mura, J. Nicolas, P. Couvreur, Nat.
Mater. 2013, 12, 991.
[12] G. Yang, J. Liu, Y. Wu, L. Feng, Z. Liu, Coord. Chem. Rev. 2016, 320–321,
100.
[13] a) D.-H. Qu, Q.-C. Wang, Q.-W. Zhang, X. Ma, H. Tian, Chem. Rev. 2015,
115, 7543; b) S. Yagai, T. Karatsu, A. Kitamura, Chem. Eur. J. 2005, 11,
4054.
ure 4F) revealed the formation of spherical nanoparticles
having a distribution of sizes, with large ones being 80 nm in
diameter and without a distinct boundary to depict a vesicular
double-layer.[33] The packing mode of 23À within organic nano-
particles is, at this point, difficult to envision yet the formation
of already described micelle-like aggregates (MLAs)[2f] from am-
phiphilic block-copolymers containing a hydrophobic interior
and hydrophilic surface presents an intriguing hypothesis that
remains to be elucidated.[34]
Conclusions
In conclusion, the photoinduced electron transfer (PET) decar-
boxylation[19] of baskets comprising three glutamic acids at the
rim is a regioselective, consecutive and quantitative reaction
that gives rise to an amphiphilic host. The host assembles into
stable, spherical and organic nanoparticles.[35] Alongside the ca-
pacity of amino acid functionalized baskets to trap nerve
agent simulants,[17,23] small hydrocarbons[36] or other comple-
mentary guests,[37] here described light-induced formation of
organic nanoparticles[38] offers a potential[39] for creating soft
materials capable of (a) spatial and temporal removal of target-
ed molecules by their encapsulation in the interior of nanopar-
ticles, (b) release of molecules induced by the nanoparticle for-
mation and finally (c) control of chemical reactivity in complex
chemical environments. Indeed, the use of UV light as a stimu-
lus can be damaging to biological tissues to, at present, limit a
direct application of our system for in vivo drug delivery. De-
spite this limitation, these findings lend themselves to applica-
tions related to the selective removal of toxic substances from
environment and/or controlling chemical non-orthogonal reac-
tions in systems chemistry. Our plan is to continue with pursu-
ing such objectives.
[14] a) J. T. van Herpt, J. Areephong, M. C. A. Stuart, W. R. Browne, B. L. Ferin-
ga, Chem. Eur. J. 2014, 20, 1737; b) K. Higashiguchi, G. Taira, J.-i. Kitai, T.
Hirose, K. Matsuda, J. Am. Chem. Soc. 2015, 137, 2722; c) T. Hirose, F.
Helmich, E. W. Meijer, Angew. Chem. Int. Ed. 2013, 52, 304; Angew. Chem.
2013, 125, 322.
[15] L. Stricker, E.-C. Fritz, M. Peterlechner, N. L. Doltsinis, B. J. Ravoo, J. Am.
Chem. Soc. 2016, 138, 4547.
[16] A. Soldevilla, A. G. Griesbeck, J. Am. Chem. Soc. 2006, 128, 16472.
[17] S. E. Border, R. Z. Pavlovic, L. Zhiquan, J. D. Badjic, J. Am. Chem. Soc.
2017, 139, 18496.
[18] K.-D. Warzecha, H. Goerner, A. G. Griesbeck, J. Phys. Chem. A 2006, 110,
3356.
[19] A. G. Griesbeck, W. Kramer, M. Oelgemoller, Synlett 1999, 1169.
[20] a) A. G. Griesbeck, A. Henz, K. Peters, E.-M. Peters, H. G. von Schnering,
Angew. Chem. Int. Ed. Engl. 1995, 34, 474; Angew. Chem. 1995, 107, 498;
b) M. Horvat, K. Mlinaric-Majerski, N. Basaric, Croat. Chem. Acta 2010, 83,
179.
Acknowledgements
[21] L. Wang, T. Neal, S. Chen, J. D. Badjic, Chem. Eur. J. 2017, 23, 8829.
[22] H. Shigemitsu, I. Hamachi, Chem. Asian J. 2015, 10, 2026.
[23] Y. Ruan, E. Dalkilic, P. W. Peterson, A. Pandit, A. Dastan, J. D. Brown, S. M.
Polen, C. M. Hadad, J. D. Badjic, Chem. Eur. J. 2014, 20, 4251.
[24] M. Kamieth, F.-G. Klarner, F. Diederich, Angew. Chem. Int. Ed. 1998, 37,
3303; Angew. Chem. 1998, 110, 3497.
[25] E. Harder, W. Damm, J. Maple, C. Wu, M. Reboul, J. Y. Xiang, L. Wang, D.
Lupyan, M. K. Dahlgren, J. L. Knight, J. W. Kaus, D. S. Cerutti, G. Krilov,
W. L. Jorgensen, R. Abel, R. A. Friesner, J. Chem. Theory Comput. 2016,
12, 281.
This work was financially supported with funds obtained from
the National Science Foundation under CHE-1606404. We
would like to thank Dr. Tanya L. Whitmer, Dr. Alexandar L.
Hansen and Dr. Chunhua Yuan from the Ohio State University
for their assistance with NMR experiments.
Conflict of interest
[26] Y. Ruan, S. Chen, J. D. Brown, C. M. Hadad, J. D. Badjic, Org. Lett. 2015,
17, 852.
[27] Y. Sato, H. Nakai, T. Mizoguchi, M. Kawanishi, Y. Hatanaka, Y. Kanaoka,
Chem. Pharm. Bull. 1982, 30, 1263.
The authors declare no conflict of interest.
[28] a) S. Chen, Y. Ruan, J. D. Brown, J. Gallucci, V. Maslak, C. M. Hadad, J. D.
Badjic, J. Am. Chem. Soc. 2013, 135, 14964; b) S. Chen, Y. Ruan, J. D.
Brown, C. M. Hadad, J. D. Badjic, J. Am. Chem. Soc. 2014, 136, 17337.
[29] L. K. S. von Krbek, C. A. Schalley, P. Thordarson, Chem. Soc. Rev. 2017, 46,
2622.
Keywords: cavitands
nanoparticles · photoresponsive system · self-assembly
·
molecular recognition
·
organic
[1] a) G. M. Whitesides, B. Grzybowski, Science 2002, 295, 2418; b) T. Aida,
E. W. Meijer, S. I. Stupp, Science 2012, 335, 813; c) R. Dong, Y. Zhou, X.
Huang, X. Zhu, Y. Lu, J. Shen, Adv. Mater. 2015, 27, 498; d) U. G. K.
Wegst, H. Bai, E. Saiz, A. P. Tomsia, R. O. Ritchie, Nat. Mater. 2015, 14, 23.
[2] a) A. Wang, J. Huang, Y. Yan, Soft Matter 2014, 10, 3362; b) M. R. Jones,
C. A. Mirkin, Nature 2012, 491, 42; c) L. S. Shimizu, S. R. Salpage, A. A.
Korous, Acc. Chem. Res. 2014, 47, 2116; d) S. I. Stupp, L. C. Palmer, Chem.
[30] D. Yu, F. Huang, H. Xu, Anal. Methods 2012, 4, 47.
[31] D. G. Duff, C. H. Giles, J. Colloid Interface Sci. 1972, 41, 407.
[32] L. E. Franken, E. J. Boekema, M. C. A. Stuart, Adv. Sci. 2017, 4, 1600476.
[33] H. Cui, T. K. Hodgdon, E. W. Kaler, L. Abezgauz, D. Danino, M. Lubovsky,
Y. Talmon, D. J. Pochan, Soft Matter 2007, 3, 945.
[34] D. Horn, J. Rieger, Angew. Chem. Int. Ed. 2001, 40, 4330; Angew. Chem.
2001, 113, 4460.
&
&
Chem. Eur. J. 2018, 24, 1 – 8
www.chemeurj.org
6
ꢀ 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Full Paper
[35] a) L. M. Negron, T. L. Diaz, E. O. Ortiz-Quiles, D. Dieppa-Matos, B.
Madera-Soto, J. M. Rivera, Langmuir 2016, 32, 2283; b) L. M. Negron, Y.
Melendez-Contes, J. M. Rivera, J. Am. Chem. Soc. 2013, 135, 3815; c) H.
Xing, Y. Bai, Y. Bai, L. H. Tan, J. Tao, B. Pedretti, G. A. Vincil, Y. Lu, S. C.
Zimmerman, J. Am. Chem. Soc. 2017, 139, 3623.
[38] K. Pan, Q. Zhong, Annu. Rev. Food Sci. Technol. 2016, 7, 245.
[39] a) R. Kuai, D. Li, J. Moon James, A. Schwendeman, Y. E. Chen, ACS Nano
2016, 10, 3015; b) S. Mitragotri, P. Stayton, MRS Bull. 2014, 39, 219.
Manuscript received: July 18, 2018
Revised manuscript received: August 17, 2018
[36] Y. Ruan, P. W. Peterson, C. M. Hadad, J. D. Badjic, Chem. Commun. 2014,
50, 9086.
Accepted manuscript online: August 21, 2018
[37] K. Hermann, Y. Ruan, A. M. Hardin, C. M. Hadad, J. D. Badjic, Chem. Soc.
Rev. 2015, 44, 500.
Version of record online: && &&, 0000
Chem. Eur. J. 2018, 24, 1 – 8
www.chemeurj.org
7
ꢀ 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Full Paper
FULL PAPER
Filling the basket: Photoinduced decar-
boxylation of molecular baskets func-
tionalized with glutamic acids was
found to, in water, give amphiphilic cav-
itands. These cavitands assemble into
organic nanoparticles that could be
used for scavenging toxic molecules,
promoting chemical reactions or deliv-
ering drugs.
&
Photoresponsive Materials
´
S. E. Border, R. Z. Pavlovic, L. Zhiquan,
M. J. Gunther, H. Wang, H. Cui,
´
J. D. Badjic*
&& – &&
Light-Triggered Transformation of
Molecular Baskets into Organic
Nanoparticles
&
&
Chem. Eur. J. 2018, 24, 1 – 8
www.chemeurj.org
8
ꢀ 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!