Molecular luminogens based on restriction of intramolecular motions through host-guest inclusion for cell imaging

Article abstract of DOI:10.1039/c3cc48625g

We developed a new strategy to restrict the motions of AIE molecules through host-guest inclusion, affording a catalogue of new molecular luminogens.

Full text of DOI:10.1039/c3cc48625g

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Molecular luminogens based on restriction of
intramolecular motions through host–guest
inclusion for cell imaging†
Cite this: Chem. Commun., 2014,
0, 1725
5
Received 12th November 2013,
Accepted 5th December 2013
abc
ab
ab
ab
ab
Guodong Liang, abJdacky W. Y. Lam, Wei Qin, Jie Li, Ni Xie and
Ben Zhong Tang*
DOI: 10.1039/c3cc48625g
www.rsc.org/chemcomm
We developed a new strategy to restrict the motions of AIE mole-
Host–guest inclusion has attracted considerable attention in
cules through host–guest inclusion, affording a catalogue of new recent years for its wide applications in nano-machines, smart
6
molecular luminogens.
materials and so on. The guest molecules are accommodated
inside the cavity of the host driven by physical interactions such
Luminogenic molecules with aggregation-induced emission (AIE) as hydrophobic interaction, which offers a new opportunity for
characteristics show strong light emission in the solid state and have the preparation of new AIE luminogens. However, the utilization
attracted increasing interest recently due to their potential applications of host–guest inclusion to restrict the motions of AIE molecules
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in biosensing, electroluminescent devices, cell imaging and so on.
is unprecedented to the best of our knowledge.
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Since our group reported the first AIE molecule in 2001, a large
Herein, we report a new strategy for constructing single mole-
number and a wide variety of AIE molecules have been synthesized cular luminogens through host–guest inclusion between cyclo-
based on the mechanism of restriction of intramolecular motions dextrins (CDs) and TPE. As a proof-of-concept demonstration,
(RIM). Jiang and coworkers restricted the rotation of tetraphenyl- TPE functionalized with a-, b- or g-CD is selected as a model
ethene (TPE) by its confinement in the intermolecular network, compound. We demonstrated that the phenyl rings of TPE resided
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affording a catalogue of emissive conjugated microporous polymers.
in the cavity of CD, which restricted their motions and hence turned
Our group enhanced the emission efficiency of TPE in the solution the fluorescence of non-emissive TPE on (Scheme 1). Since only
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state by locking its phenyl rings via covalent bonding. Dinca and physical interaction is involved, the effect of motion restriction on
coworkers immobilized functionalized TPE within rigid metal–organic the light emission process can be identified. Moreover, given their
framework through coordination polymerization, which turned its high emission efficiency and good biocompatibility inherited from
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fluorescence on. While chemical approaches have proved to be TPE and CD, the fluorescent inclusion complexes are promising for
efficient in restricting the intramolecular motions, they involve biological applications.
variations in energy levels and molecular structures, both of which
play important roles in the light emission process. This makes the by esterification reaction of CD with mono-carboxylic acid-substituted
effect of RIM process ambiguous and plausible. Thus, development TPE (TPE–CO H Scheme S1, ESI†). Detailed procedures for the
of physical processes with minimal chemical reactions to restrict synthesis of TPE–CO H and TPE–CDs were described in the ESI.†
All the intermediates and desirable products were characterized using
The CD-decorated tetraphenylethenes (TPE–CDs) were synthesized
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the intramolecular motions is highly desirable.
NMR and mass spectrometry and satisfactory results were obtained
a
HKUST-Shenzhen Research Institute, No. 9 Yuexing 1st RD, South Area,
Hi-tech Park, Nanshan, Shenzhen, China 518057
b
Department of Chemistry, Institute for Advanced Study, Division of Biomedical
Engineering and Institute of Molecular Functional Materials, The Hong Kong
University of Science and Technology, Clear Water Bay, Hong Kong, China.
E-mail: tangbenz@ust.hk
c
DSAP lab, PCFM lab, School of Chemistry and Chemical Engineering,
Sun Yat-Sen University, Guangzhou 510275, China
d
Guangdong Innovative Research Team, SCUT-HKUST Joint Research Laboratory,
State Key Laboratory of Luminescent Materials and Devices, South China
University of Technology, Guangzhou 510640, China
†
Electronic supplementary information (ESI) available: Materials and instru-
ments, synthesis and characterization of the TPE-CDs, and NMR, mass, UV and
CD spectra are supplied as supporting information. See DOI: 10.1039/c3cc48625g
Scheme 1 Schematic illustration of tetraphenylethene trapped inside the
cavity of cyclodextrin.
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Scheme 2 (A) Chemical structure and (B) schematic illustration of the
geometric structure of TPE–b-CD.
In contrast, these peaks were still observed in the concentrated
solution of TPE–g-CD, demonstrating the less restriction of g-CD on
the mobility of TPE (Fig. S18, ESI†). Taking the signal at d 7.9 as a
reference, TPE–a-CD and TPE–g-CD exhibited the weakest and
strongest absorption peaks at d 7.1 and 6.9, respectively. The smaller
cavity of a-CD restricted the motions of phenyl rings of TPE to a
greater extent than g-CD with a larger cavity size (Table S1, ESI†),
thus resulting in weak aromatic signals.
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Fig. 1 H NMR spectra of (A) TPE–CO
2
H and (B) TPE–b-CD in DMSO-d
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.
corresponding to their molecular structures (Fig. S1–S11; ESI†). The
The UV spectra of all the TPE–CDs showed a broad absorption
H NMR spectrum of TPE–b-CD as well as that of TPE–CO
H is shown band at 314 nm, which was blue-shifted from that of the TPE
in Fig. 1 as an example. A distinct signal attributed to the resonances derivative (TPE–C2) carrying no CD substituent (Fig. S19, ESI†). This
of the phenyl protons adjacent to the ester group (a in Fig. 1) was indicated that the TPE unit of TPE–CDs adopted a more twisted
observed at d 7.9. The absorptions of other protons (b , c and d ) at conformation in order to fit into the cavity of CD driven by hydro-
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2
0
0
0
0
d 7.1 and 6.9 were broad and weak, which was related to the slow phobic interaction between the two components. Such interaction
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relaxation due to the restriction of their intramolecular motions.
was verified using circular dichroism (CD) spectroscopy. A positive
Nuclear overhauser enhancement (NOE) cross-peaks between the TPE signal appeared in the absorption region of TPE in the CD spectra of
protons and the interior protons of CD cavity were observed in the 2D all the TPE–CDs, suggesting that the CD unit induced the TPE moiety
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0
ROESY NMR spectrum of TPE–b-CD, indicating that they were closely to pack in a helical fashion (Fig. S20, ESI†).
coupled. This also suggested that most of the phenyl rings of TPE
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The fluorescence (FL) behaviors of the TPE–CDs are shown
were immobilized in the CD cavity (Fig. S12, ESI†). On the other hand, in Fig. 2. The dilute dimethylsulfoxide (DMSO) solution of TPE
no NOE signals were detected between the resonance peak at d 7.9 emitted weakly at 470 nm due to the intramolecular motions of
and those inside the b-CD cavity because they were far away from the phenyl rings, which had efficiently consumed the energy of
each other. Similar results were found in TPE–a-CD and TPE–g-CD the excited states through nonradiative relaxation channels. In
(
Fig. S13 and S14, ESI†). From these results, the geometric a sharp contrast, TPE–b-CD showed a stronger FL at 410 nm,
structure of TPE–b-CD and the optimized chemical structure of which was 60 nm blue-shifted from that of unsubstituted TPE
TPE are schematically illustrated in Scheme 2 and Scheme S2 (Fig. S21, ESI†). The enhanced fluorescence revealed that the
(
ESI†). While most of phenyl rings are restricted by cyclodextrin, motions of the phenyl rings of TPE–b-CD were somewhat restricted
some of them are still free for motion.
and stemmed from the formation of the inclusion complex.
1
The H NMR signals of TPE–b-CD were concentration-dependent. The TPE unit included in the CD cavity possessed a more
The peaks at d 7.1 and 6.9 disappeared in highly concentrated solution
(Fig. S15, ESI†), which illustrated the formation of an intermolecular
complex. It has been well known that adamantane has a strong and
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specific interaction with cyclodextrin. Adamantane enters preferentially
into the cavity of cyclodextrin to form the inclusion complex as
compared with phenyl derivatives. After mixing with adamantane, the
absorption peaks at d 7.1 and 6.9 were clearly intensified (Fig. S16, ESI†)
because part of the phenyl rings were driven out from the cavity of b-CD
owing to the strong and specific interaction of adamantane with CD.
This further confirmed the formation of the intermolecular complex in
high concentrated solution.
The effect of cavity size of the CD on the RIM process was
then investigated. Similarly to TPE–b-CD, the dilute solution of
TPE–a-CD exhibited two broad peaks at d 7.1 and 6.9, which
Fig. 2 (A) Fluorescence spectra and (B) quantum yield of TPE–CDs, bare TPE
and TPE–CD mixtures (1 : 1 molar ratio) in DMSO solutions. Inset in (B):
fluorescent photos of TPE–CDs, bare TPE and TPE–CD mixtures (1 : 1 molar
disappeared in high concentrated solution (Fig. S17, ESI†). ratio) in DMSO solutions taken under UV irradiation. Concentration: 5 mM.
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twisted conformation, thus resulting in a blue-shift in the fluores- emitted upon UV irradiation, revealing that TPE–b-CD was able
cence. Compared to TPE–a-CD, TPE–b-CD showed a weaker FL at to penetrate the cell membrane and worked as a fluorescent
410 nm but emitted stronger than TPE–g-CD. The physical mixtures visualizer for intracellular imaging.
of TPE and CDs (TPE–CDs) radiated weakly at 470 nm in DMSO In summary, we have developed a new strategy to restrict
solutions under the same experimental conditions. The quantum the motions of AIE molecules through host–guest inclusion,
yields of the TPE–CDs and their physical mixtures were determined leading to the formation of a catalogue of new molecular
using quinine sulfate as a reference (Fig. 2B). Bare TPE showed a low luminogens. The phenyl rings of TPE were included in the
quantum yield (0.5%) in DMSO. On the other hand, TPE–b-CD cavity of cyclodextrins, resulting in enhanced fluorescence due to
exhibited a 20-fold higher value. The value was further enhanced by the restriction of their motions. The quantum yield of the TPE–
mixing with adamantane, presumably due to the further activation CDs increased upon decreasing the cavity size of the cyclodextrin.
of the RIM process by the bulky size of adamantane. Among the The TPE–CDs were biocompatible and could be utilized to image
TPE–CDs, TPE–a-CD exhibited the highest FL quantum yield the cytoplasm of living cells.
because the smaller cavity of a-CD restricted the motions of phenyl
This work was partially supported by the National Basic
rings more efficiently than the larger-sized g-CD cavity. Since all the Research Program of China (973 Program; 2013CB834701), the
TPE–CD mixtures exhibited low quantum yields, it demonstrated Research Grants Council of Hong Kong (HKUST2/CRF/10 and
that covalent bonding of TPE with cyclodextrin is crucial for the N_HKUST620/11) and the University Grants Committee of
formation of the inclusion complex. The melding of TPE and CD Hong Kong (AoE/P-03/08). B.Z.T. is thankful for the support
into one molecule had brought the two units close together, making from Guangdong Innovative Research Team Program of China
the inclusion of the phenyl rings to the cavity of CD more easy.
(201101C0105067115). G.D.L is thankful for the support from the
To further verify the mechanism of the emission enhancement, Hong Kong Scholar Program (XJ2011047) and NSFC (21374136).
time-resolved fluorescence measurements were carried out. The
emission of bare TPE decayed exponentially with a lifetime of Notes and references
1
.41 ns (Fig. S22 and Table S2, ESI†). In contrast, the excited state
1
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7
ꢁ1
non-radiative decay rate constant (10.2 ꢀ 10 s ) and by a far
2
7
ꢁ1
higher radiative decay rate constant (1.94 ꢀ 10 s ) as compared
7
ꢁ1
7
ꢁ1
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Fig. 3 (A) Bright-field and (B) fluorescent images of HeLa cells incubated
with TPE–b-CD.
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Chem. Commun., 2014, 50, 1725--1727 | 1727