Tunable Aggregation-Induced Emission Nanoparticles by Varying

Subscriber access provided by University of South Dakota

Article

Tunable Aggregation-Induced Emission Nanoparticles by Varying Isolation Groups in Perylene Diimide Derivatives and Application in Three-Photon Fluorescence Bio-Imaging Luyi Zong, Hequn Zhang, Yaqin Li, Yanbin Gong, Dongyu Li, Jiaqiang Wang, Zhe Wang, Yujun Xie, Mengmeng Han, Qian Peng, Xuefeng Li, Jinfeng Dong, Jun Qian, Qianqian Li, and Zhen Li ACS Nano, Just Accepted Manuscript • DOI: 10.1021/acsnano.8b05090 • Publication Date (Web): 22 Aug 2018 Downloaded from http://pubs.acs.org on August 22, 2018

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 26 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

Tunable Aggregation-Induced Emission Nanoparticles by Varying Isolation Groups in Perylene Diimide Derivatives

and

Application

in

Three-Photon

Fluorescence Bio-Imaging Luyi Zong,†ǁ Hequn Zhang, ‡ǁ Yaqin Li,†ǁ Yanbin Gong, † Dongyu Li, ‡ Jiaqiang Wang, † Zhe Wang, † Yujun Xie,† Mengmeng Han,† Qian Peng,§ Xuefeng Li,† Jinfeng Dong,† Jun Qian,* ‡ Qianqian Li,* † and Zhen Li* †, # †

Department of Chemistry, Wuhan University, Wuhan 430072, China

‡

State Key Laboratory of Modern Optical Instrumentations, Center for Optical and Electromagnetic

Research, Joint Research Laboratory of Optics of Zhejiang Normal University and Zhejiang University, Zhejiang University, Hangzhou 310058, China §

Institute of Chemistry, the Chinese academy of sciences, Beijing, 100124, P. R. China

#

Institute of Molecular Aggregation Science, Tianjin University, Tianjin 300072, China

ǁ

These authors contributed equally to this work.

* To whom correspondence should be addressed:

[email protected] (Z. Li)

ACS Paragon Plus Environment

1

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 2 of 26

[email protected] (Q. Li)

[email protected] (J. Qian)

ABSTRACT: The development of fluorogens with deep-red emission is one of the hottest topics of investigation in the field of bio/chemosensors and bioimaging. Herein, the tunable fluorescence of perylene diimide (PDI) derivatives was achieved by the incorporation of varied isolation groups linked on the PDI core. With the enlarged sizes of isolation groups, the conversion from aggregation caused quenching (ACQ) to aggregation-induced emission (AIE) was obtained in their fluorescence variations from solutions to nanoparticles, as the result of the efficient inhibition of π-π stacking by the larger isolation groups. Accordingly, DCzPDI bearing 1,3-di(9H-carbazol-9-yl)benzene as the biggest isolation group exhibited the bright deep-red emission in the aggregated state with a quantum yield of 12.3%. Combined with the three-photon excited fluorescence microscopy (3PFM) technology, through-skull 3PFM imaging of mouse cerebral vasculature can be realized by DCzPDI nanoparticles with good biocompatibility, and the penetration depth can be as deep as 450 μm. KEYWORDS: three-photon excited fluorescence microscopy, perylene diimide, aggregation-induced emission, isolation group, deep-red emission


2

Page 3 of 26 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

Fluorescence imaging plays a major role in both basic biological research and clinical diagnostics for high spatial resolution, no radiation, abundant signals, and fast response.1,2 The emission wavelengths in the deep red region are highly desirable for in vivo observations, owing to the low background fluorescence, small light scattering, deep penetration and less damage to biological samples.3,4 Moreover, with the development of fluorescence techniques, the excitation of some organic materials with femtosecond (fs) laser pulses can yield three-photon absorption (3PA), which allows the excitation wavelength of threephoton excited fluorescence microscopy (3PFM) imaging in the near-infrared (NIR) region (1000-1700 nm).5,6 In comparison with some other approaches for the real-time monitoring of the dynamic blood flow process, such as laser doppler flowmeter,7 ultrasonic doppler flowmeter,8 optical doppler tomography9 and laser speckle imaging,10 long-wavelength fs laser excitation of 3PFM imaging with reduced photon scattering is able to effectively penetrate the skull and tightly focus onto the biological tissues beneath, generating bright three-photon fluorescence for deep-tissue imaging. Thus, it becomes quite promising to observe brain structure and related activities in real time for high spatial resolution, and can realize deeptissue bioimaging for a multiphoton fluorescence process. For the application of organic dyes in the 3PFM imaging as nanoparticles, the bright deep-red emission in the aggregated state is favorable and essential, which can be realized by the reasonable design of organic molecules with special structures and electron properties.11 Additionally, the chemical and photostability is also very important for 3PFM imaging, as the same to other practical applications of organic luminogens. 12-14

Perylenetetracarboxylic diimide (PDI) derivatives were previously utilized in the fields of paints and lacquers, because of their outstanding chemical, thermal, and photochemical stability.15,16 Later, their applications have been expanded to high-tech applications, such as photovoltaic cells, optical switches, lasers, and light emitting diodes.17-22 Thanks to the planar structure of PDI with strong electronwithdrawing ability, PDI derivatives can offer bright emissions in long wavelength region as the isolated state with high exciton stability. ACS Paragon Plus Environment

3

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 4 of 26

In comparison with conventional molecular scale contrast agents, nanoparticles promise improved abilities for in vivo detection and potentially enhanced targeting efficiencies through longer engineered circulation times, designed clearance pathways, and multimeric binding capacities.23-26 However, when PDI derivatives are applied into the physiological environment as nanoparticles in bioimaging, the strong π-π stacking of PDI plane in the aggregated state often weakens or quenches light emission. This is a common phenomenon widely known as “aggregation-caused quenching” (ACQ), directly limiting their application in fluorescence detection as nanoparticles. Thus, the suppression of π-π stacking is essential to achieve the bright emission in the aggregated state, which can be realized by introduction of various aromatic rings as isolation groups from the sides. This strategy has been well confirmed in our previous research, with good performance achieved for the avoidance of strong intermolecular π-π interactions.27-33 Thus, a series of PDI-based organic molecules with different substitutes as isolation groups have been designed and synthesized, with their structures shown in Chart 1. While the introduction of phenyl and biphenyl moieties as the isolation groups to the two sides of PDI core in SPhPDI and DPhPDI, could not suppress the strong π-π stacking of the PDI core efficiently, carbazole moieties with larger sizes were utilized for the construction of SCzPDI and DCzPDI. Excitedly, the enhanced fluorescence in the aggregated state has been realized, exhibiting the typical characteristic of aggregation-induced emission (AIE).34-36 This ACQ-to-AIE conversion further confirms the magic role of isolation groups in the regulation of emission property in the aggregated state. More importantly, the fabricated nanoparticles of DCzPDI exhibited very bright deep-red fluorescence under the excitation of a 1550 nm fs laser. Once applied to the 3PEFM in vivo imaging of blood vessels of mouse brain, the high spatial resolution could be achieved with the penetration depth of 450 m.


4

Page 5 of 26 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

Chart 1. Chemical structures of PDI-based organic molecules with different isolation groups

RESULTS AND DISCUSSION The four PDI derivatives with different isolation groups were synthesized simply by Suzuki-Coupling reaction between bromine-substituted PDIs and corresponding borate esters conveniently, with the detailed syntheses described in the experimental section. As to SPhPDI, the isolation group was the phenyl moiety, the smallest one in this system. Then, the twisted structures of isolation groups were built by the linkage of different aromatic rings to meta-position of the involved phenyl unit, and the substituted aromatics varied from one phenyl (DPhPDI) to one carbazolyl (SCzPDI), then to two carbazolyl (DCzPDI) moieties. Thus, the sizes of isolation groups in spatial configuration became larger and larger gradually, which was beneficial to suppressing the π-π stacking in the aggregated state. Also, owing to the introduction of long alkyl chains to PDI core, all the target molecules showed good solubility in common organic solvents, such as cyclohexane, toluene, DCM, THF and so on.


5

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 6 of 26

Scheme 1. Synthetic routes of four PDI derivatives.

The fluorescent properties of these PDI derivatives in the aggregated state varied much with different isolation groups. As shown in Figure 1A and Figure S1, the emission of SPhPDI and DPhPDI in solution decreased gradually with the addition of methanol as the poor solvent, which was accompanied with the formation of aggregated state. This common ACQ effect was usually due to the strong π-π interaction among adjacent molecules.37,38 However, for SCzPDI and DCzPDI bearing bigger isolation groups, the opposite trend could be observed that the fluorescence intensity was enhanced with the increasing fractions of methanol (fm). And the highest emission intensities were achieved at fm of 90%, which were 24- and 30-folds of the original ones, respectively. This ACQ-to-AIE conversion was mainly due to the tunable molecular packing modes and intermolecular interactions in the aggregated state by the variation of isolation groups.39


6

Page 7 of 26 35

1.6

(A) SPhPDI DPhPDI SCzPDI DCzPDI

21

(B)

1.2

SPhPDI DPhPDI

I/I0

28

I/I0

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

0.8

Solution Nanoparticle Solid

14

SCzPDI DCzPDI

0.4 7 DCzPDI

0.0

0 0

30

fm (%)

60

90

c-Hexane Toluene THF

DCM

Figure 1. (A) The changes of fluorescence intensities of PDI derivatives in DCM solution with the addition of different fractions of methanol (fm), inset: the photos of DCzPDI in different conditions under UV lamp; (B) The changes of fluorescence intensity of PDI derivatives in different solvents.

Basically, the isolation groups with twisted configurations and big sizes could enlarge the distances between π-plane efficiently, resulting in the bright deep-red emission of DCzPDI as nanoparticles (Figure 1A). However, the fluorescence intensity of DCzPDI in solution is not always enhanced in the formation of nanoparticles by the addition of methanol, it decreased slightly as fm in the region of 10%-30%, which may be related to the varied polarities of solvent systems. Thus, with the aim to investigate the effect of solvents with different polarities on their emission properties, the fluorescence spectra of these PDI derivatives in cyclohexane, toluene, tetrahydrofuran (THF) and dichloromethane (DCM) were conducted as shown in Figure 1B and Figure S2. Interestingly, SCzPDI and DCzPDI with AIE property showed the intensive fluorescence quenching effect with the increased polarities of solvents, however, it was not so obvious in the ACQ ones with the similar conditions. This different behaviors meant that the intramolecular charge transfer in the two kinds of PDI derivatives was changed with the incorporation of varied isolation groups, which could be proved by theoretical calculation. ACS Paragon Plus Environment

7

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 8 of 26

Figure 2. Frontier orbitals of PDI derivatives optimized at the B3LYP/6-31G* level40

As shown in Figure 2, time-dependent DFT (TD-DFT) calculations indicated the local excitation (LE) character of SPhPDI and DPhPDI with the overlap of their HOMOs and LUMOs, which were mainly located at the PDI core with little electron distribution on the isolation groups. However, for the AIE-active molecules, SCzPDI and DCzPDI exhibited the charge transfer (CT) nature for the spatially separated HOMOs and LUMOs. Their HOMOs were restricted on the isolation groups, while LUMOs were distributed to PDI unit. The dihedral angles between these two moieties were about 64o, and the introduction of carbazole unit in SCzPDI and DCzPDI could enhance the electron-donating abilities of isolation groups, which were beneficial to the formation of twisted intramolecular charge transfer under excitation. Thus, the solvation effects of SCzPDI and DCzPDI were reasonable, since the CT state was heavily depended on the polarity of environment. It further confirmed that the enhanced emissions of ACS Paragon Plus Environment

8

Page 9 of 26

nano-particles with the addition of methanol was due to the formation of aggregated state, not the polarity of solvents. Accordingly, the excited states of PDI derivatives may exhibit different intrinsic properties for different electron transition processes, resulting in the varied fluorescence properties as a single molecule. Also, the packing modes of PDI derivatives in the aggregated states could be adjusted by the different electrostatic potentials of isolation groups. However, for either benzene or carbazole moieties as isolation groups, they are aromatic rings with rigid structures, which can suppress strong π-π interactions of planar PDI moieties efficiently by the twisted configurations. With the enlarged sizes of isolation groups from SPhPDI to DCzPDI, the distances between PDI moieties can be enlarged gradually, leading to the bright emission in the aggregated state.

Solution

Film

SPhPDI DPhPDI SCzPDI DCzPDI

Normalized intensity (au)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

550

650

750

850

Wavelength (nm)

Figure 3. Fluorescence spectra of PDI derivatives in solutions and thin films

Also, the photostabilities of PDI derivatives in aqueous solution were investigated by time-dependent fluorescence experiments under continuous illumination. During the continuous irradiation of 1 hour, no ACS Paragon Plus Environment

9

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 10 of 26

obvious changes were observed in the fluorescence intensity, confirming their excellent photostabilities derived from the PDI core (Figure S4). This is favorable to the application in the field of bio/chemosensors and bioimaging, especially for long-term 3PF imaging. Also, they possessed excellent thermal stability with the decomposition temperatures (the 5% of weight lost) higher than 405 oC (Figure S5). With the aim to investigate their light emission properties in aggregated states in detail, the absorption and fluorescence spectra of these PDI derivatives in solid state were conducted (Figure 3 and Figure S3). The absorption spectra of SCzPDI and DCzPDI red-shifted, compared to that of SPhPDI and DPhPDI, mainly due to the different modes of electron transitions through the whole molecules and packing modes in aggregated state. Apart from the different fluorescence intensities in thin film for the ACQ or AIE effect, their maximum emission wavelengths (λmaxs) were different due to the varied isolation groups. Since they exhibited the similar λmaxs in solution as the isolation states (Figure 3), these various red-shifts were mainly due to the different intermolecular interactions and packing modes with the varied molecular conformation. Among them, DCzPDI demonstrated the minimal λmax of 638 nm, while those of others were about 660 nm, suggesting that the π-π stacking of DCzPDI in aggregated state has been partially inhibited by the largest isolation group with twisted configuration. Accordingly, the high fluorescence quantum yield of 12.3% was achieved in the solid state (Figure S6). Considering the strong fluorescence of DCzPDI in aggregated state, DCzPDI nanoparticles (DCzPDI-NPs) were fabricated by a modified nanoprecipitation approach using Pluronic F-127 (F127) as the encapsulation matrix (Figure 4A).41 These nanoparticles exhibited good photostability under continuous laser excitation (450 nm, 100 mW). After three hours of exposure, the fluorescence intensity of DCzPDI-NPs still remained 79% (Figure S7). The morphology of DCzPDI-NPs was characterized by transmission electron microscope (TEM), and the average hydrodynamic diameter for DCzPDI-NPs was measured to be about 100 nm by dynamic light scattering (DLS) (Fig. S8). A bright deep-red emission (λmax at 658 nm) with the quantum yield (Φ) of 2.37% was observed from the single photon fluorescence spectrum of DCzPDI-NPs in water (Figure S9). ACS Paragon Plus Environment

10

Page 11 of 26 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

Figure 4. (A) A schematic illustration of the preparation of DCzPDI-NPs with F127 as the encapsulation matrix; (B) Nonlinear optical response of DCzPDI-NPs in aqueous dispersion, under the 1550 nm fs laser excitation, inset: power dependence relationship of the fluorescence from DCzPDI-NPs under the 1550 nm fs laser excitation.

Under the excitation of a 1550 nm fs laser (FLCPA-01C, Calmar Laser, 400 fs, 1 MHz), the nonlinear optical response of DCzPDI-NPs was studied on a lab-built fluorescence measuring system. As shown in Figure 4B, the three-photon fluorescence (3PF) spectrum was similar to the single-photon one, with the peak at 650 nm and its tail extending into near-infrared range. Under the lab-built fluorescence measuring system, a good linear relationship between the logarithm of fluorescence intensity of DCzPDI-NPs and the logarithm of the excitation power (Pin) was observed with the slope of 2.71 (close to 3), suggesting that 3PF was the main nonlinear optical process. The three-photon cross-section of DCzPDI-NPs was calculated to be 6.80×10-80 cm6 s2 via the nonlinear transmissivity method,42 much larger than that of commonly used organic dye Rh6G (6×10−81 cm6 s2).43 Furthermore, the lifetime of DCzPDI-NPs was subsequently acquired to be 7.38 ns by a time-correlated single-photon counting (TCSPC) system (Figure S10), which was distinguished from auto fluorescence arising from biological tissues. Thus, it was favorable to the tissue bioimaging for the less photon attenuation and high signal-to-noise ratio.


11

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 12 of 26

The cytotoxicity of DCzPDI-NPs was investigated by counting the viability of HeLa cells treated with DCzPDI-NPs for 48 h. Even the concentration of DCzPDI-NPs was as high as 2.0 mg/mL, the cell viability remained above 80% (Figure 5A), indicating the low cytotoxicity and good biocompatibility of DCzPDI-NPs. This could be further confirmed by the histopathology examination. As shown in Figure 5B, after 40 days post-injection of DCzPDI-NPs, mice hardly had inflammation or abnormalities on their major organs (lungs, liver, spleen, kidneys and heart) during the accumulation of DCzPDI-NPs by blood circulation. Thus, the above experiments proved that DCzPDI-NPs could act as an excellent optical nanoprobe for the application in bioimaging.

Figure 5. (A) Viability of HeLa cells treated with 0, 0.2, 0.5, 1.5 and 2.0 mg/mL DCzPDI-NPs for 48 hours; (B) Microscopic images of tissue sections harvested from mice, 40 days after the injection. Experimental group: mice were injected with PBS (1×) dispersion of DCzPDI-NPs (down). Control group: mice were injected with only PBS (1×) solution (up).

Accordingly, under the excitation of a 1550 nm fs laser, DCzPDI-NPs were utilized for in vivo imaging of the brain blood vessels of mice. As shown in Figure 6, DCzPDI-NPs exhibited a bright 3PF signal in brain blood vessels, and 3PFM imagings of brain blood vessels at various vertical depths could be obtained. Since some coarser vessels existed in the imaging depth from 0 to 100 m, the structures of capillaries can be observed in the depth of 150-450 m. Moreover, the corresponding 3D image of the DCzPDI-NPs in the blood provided a general and clear spatial picture about major blood vasculature ACS Paragon Plus Environment

12

Page 13 of 26 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

networks and tiny capillaries in detail. Furthermore, the spatial resolution (Gaussian-fitted FWHM) of 3PFM images was measured (Figure 7), and it was high enough to clearly observe the tiny blood vessel with diameter of 1.26 μm at the depth of 150 μm, and 2.39 μm at the depth of 435 μm. Thus, DCzPDINPs can be served as a deep-red 3PF probe successfully to realize the real-time monitoring of the dynamic blood flow process in vivo with high spatial resolution.

Figure 6. 3PFM imaging of brain blood vessels of a mouse treated with DCzPDI-NPs. Individual images taken at the depths of (A) 0 m, (B) 50 m, (C) 100 m, (D) 150 m, (E) 200 m, (F) 250 m, (G) 300 m, (H) 350 m, (I) 400 m and (J) 450 m, (K) A stacked three-photon fluorescence image from a depth of 0 to 450 m, (L) A reconstructed 3D image showing the distribution of the DCzPDI-NPs in blood vessels of the mouse. The scale bar: 100 µm.


13

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 14 of 26

Figure 7. 3PFM imaging of brain blood vessels of a mouse treated with DCzPDI-NPs at 150 μm (A) and 435 μm (B), full width at half-maximum (FWHM) of a blood vessel at the depth of 150 μm (C) and 435 μm (D) as indicated with the dotted white line in the corresponding image.

CONCLUSIONS In summary, four PDI derivatives with deep-red emissions were designed and synthesized by the incorporation of different isolation groups linked on the PDI core. Followed by the increased sizes of isolation groups with twisted configurations, their emission properties in aggregated states realized the opposite conversion from ACQ to AIE. For the bright deep-red fluorescence of DCzPDI bearing the largest isolation groups as nanoparticles (DCzPDI-NPs), it was applied into three-photon excited fluorescence microscopy imaging with high-resolution, and a penetration depth of 450 μm beneath the skull was achieved. Coupled with the excellent chemical stability and biocompatibility, DCzPDI-NPs have great potential for deep-tissue bioimaging in clinical fields.

EXPERIMENTAL SECTION Methods. 1H and

13

C NMR spectra were conducted with a Varian Mercury 300 spectrometer using

tetramethylsilane (TMS; δ = 0 ppm) as internal standard. UV-visible spectra were obtained using a ACS Paragon Plus Environment

14

Page 15 of 26 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

Shimadzu UV-2550 spectrometer. Fluorescence spectra were recorded with Hitachi F-4600 fluorescence spectrophotometer. Elemental analyses were performed by a CARLOERBA-1106 microelemental analyzer. HR-MS (MOLDI-TOF) spectrum was operated in Autoflex speed TOF. SEM images were captured by a JEM-2010 microscope. DLS measurements were performed on a Malvern ZEN 3600. Materials. THF was dried over and distilled from K-Na alloy under an atmosphere of argon. All other chemicals and reagents were purchased from commercial suppliers and used without further purification. The synthetic routes were shown in the supporting information. Compound 7 was synthesized according to the literature procedure.44 Synthesis of compound 3. Under an atmosphere of nitrogen, carbazole (1.672 g, 10.0 mmol) and NaH (0.360 g, 15.0 mmol) were dissolved in DMF and stirred at room temperature for 20 min, then 1-bromo3,5-difluorobenzene (1.145 g, 5.0 mmol) was added. The mixture was stirred at 80 oC for 24 h. After being cooled to room temperature, the mixture was poured into water, and then filtered. The crude product was purified by a silica gel column using dichloromethane/petroleum ether (1/3) as an eluent to give compound 1 as a white solid (300 mg, 18.6%). 1H NMR (300 MHz, CDCl3)  (ppm): 8.15 (d, J = 7.8 Hz, 2H, ArH), 7.75 (s, 1H, ArH), 7.62 (d, J = 8.7 Hz, 1H, ArH), 7.55 (t, J = 7.8 Hz, 1H, ArH), 7.41 (m, 4H, ArH), 7.33 (m, 1H, ArH), 7.27 (d, J = 7.8 Hz, 2H, ArH). Synthesis of compound 4. Under an atmosphere of nitrogen, 3 (0.300 g, 0.93 mmol), bis(pinacolato)diboron (0.343 g, 1.35 mmol), KOAc (0.034 g, 0.35 mmol), and Pd(dppf)2Cl2 (0.399 g, 0.55 mmol) were dissolved in 1,4-dioxane (40 mL). Then the mixture was stirred at 80 oC for 42 h. After being cooled to room temperature, the solvent was evaporated under reduced pressure. The crude product was purified by a silica gel column using dichloromethane/petroleum ether (1/2) as an eluent to give 4 as a white solid (343 mg, 99.7%). 1H NMR (300 MHz, CDCl3)  (ppm): 8.15 (d, J = 7.8 Hz, 2H, ArH), 7.99 (s, 1H, ArH), 7.92 (s, 1H, ArH), 7.63 (d, J = 6.9 Hz, 2H, ArH), 7.38 (s, 1H, ArH ), 7.33 (m, 4H, ArH), 7.27 (d, J = 5.4 Hz, 1H, ArH), 1.33 (m, 6H, -CH3). ACS Paragon Plus Environment

15

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 16 of 26

Synthesis of compound 5. Compound 5 was prepared according to the similar procedure for compound 3. 1-Bromo-2,5-difluorobenzene (0.772 g, 4.0 mmol), carbazole (2.675 g, 16 mmol), sodium hydride (0.288 g, 12 mmol). White solid (1.308 g, 67.0 %). 1H NMR (300 MHz, CDCl3)  (ppm): 8.13 (d, J = 7.5 Hz, 4H, ArH), 7.84 (s, 2H, ArH), 7.77 (s, 1H, ArH), 7.52 (d, J = 8.1 Hz, 4H, ArH), 7.43 (t, J = 7.2 Hz, 4H, ArH), 7.33 (t, J = 7.5 Hz, 4H, ArH). Synthesis of compound 6. Compound 6 was prepared according to the similar procedure for compound 4. Compound 5 (0.975 g, 0.2 mmol), bis(pinacolato)diboron (0.944 g, 3,71 mmol), KOAc (0.069 g, 0.70 mmol), and Pd(dppf)2Cl2 (0.073 g, 0.1 mmol). White solid (0.440 g, 41.2%). 1H NMR (300 MHz, CDCl3)  (ppm): 8.16 (d, J = 6.0 Hz, 4H, ArH), 7.84 (d, J = 3.0 Hz, 2H, ArH ), 7.52 (d, J = 6.0 Hz, 4H, ArH), 7.45 (d, J = 6.0 Hz, 4H, ArH), 7.29 (t, J = 9.0 Hz, 4H, ArH ), 1.37 (s, 12H, -CH3). Synthesis of SPhPDI. Under an atmosphere of nitrogen, compound 7 (0.207 g, 0.17 mmol), 4 (0.149 g, 1.22 mmol), K2CO3 (0.083 g, 0.60 mmol) and Pd(PPh3)4 (catalytic amount) were dissolved in THF/H2O (6 mL/1 mL). Then the mixture was refluxed for 22 h. After being cooled to room temperature, the solvent was evaporated under reduced pressure. The crude product was purified by a silica gel column using dichloromethane/petroleum ether (2/3) as an eluent to give SPhPDI as a dark-red solid (193 mg, 93.7%). 1

H NMR (300 MHz, CDCl3)  (ppm): 8.63 (s, 2H, ArH), 8.15 (d, J = 5.1 Hz, 2H, ArH), 7.83 (d, J = 5.1

Hz, 2H, ArH), 7.55 (m, 4H, ArH), 7.50 (d, J = 4.5 Hz, 6H, ArH), 4.12 (m, 4H, -CH2-), 2.0 (s, 2H, -CH-), 1.22 (m, 80H, -CH2-), 0.86 (m, 12H, -CH3). 13C NMR (75 MHz, CDCl3) δ (ppm): 163.57, 141.96, 140.89, 135.15, 134.53, 132.23, 130.06, 129.21, 128.98, 128.55, 127.41, 122.07, 121.75, 44.57, 36.55, 31.79, 31.60, 29.94, 29.53, 29.23, 26.41, 22.56, 13.98. Anal. Calcd for: C84H114N2O4: C 82.98, H 9.45, N 2.30, found: C 82.82, H 9.32, N 2.56.

Synthesis of DPhPDI. DPhPDI was prepared according to the similar procedure for SPhPDI. Compound 7 (0.244 g, 0.20 mmol), compound 2 (0.174 g, 0.88 mmol), K2CO3 (0.083 g, 0.60 mmol) and Pd(PPh3)4 (catalytic amount). Red solid (160 mg, 58.6%). 1H NMR (300 MHz, CDCl3)  (ppm): 8.68 (s, ACS Paragon Plus Environment

16

Page 17 of 26 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

2H, ArH), 8.15 (d, J = 5.1 Hz, 2H, ArH), 7.92 (d, J = 5.1 Hz, 2H, ArH), 7.81 (m, 2H, ArH), 7.71 (d, J = 7.8 Hz, 2H, ArH), 7.60 (d, J = 8.7 Hz, 6H, ArH), 7.53 (d, J = 4.2 Hz, 2H, ArH), 7.44 (t, J = 7.2 Hz, 4H, ArH), 7.37 (d, J = 6.9 Hz, 2H, ArH), 4.12 (m, 4H, -CH2-), 1.98 (s, 2H, -CH-), 1.21 (m, 80H, -CH2-), 0.85 (m, 12H, -CH3). 13C NMR (75 MHz, CDCl3)  (ppm): 163.75, 142.69, 140.97, 140.25, 135.43, 134.81, 132.59, 130.39, 129.55, 128.93, 127.97, 127.63, 127.21, 122.31, 121.99, 44.67, 36.67, 31.91, 30.08, 29.38, 26.52, 22.71, 14.15. Anal. Calcd for: C96H122N2O4: C 84.29, H 8.99, N 2.05 found: C 84.03, H 8.80, N 2.18. Synthesis of SCzPDI. SCzPDI was prepared according to the similar procedure for SPhPDI. Compound 7 (0.183 g, 0.15 mmol), compound 4 (0.166 g, 0.45 mmol), K2CO3 (0.124 g, 0.89 mmol) and Pd(PPh3)4 (catalytic amount). Red solid (90 mg, 38.8%). 1H NMR (300 MHz, CDCl3)  (ppm): 8.70 (s, 2H, ArH), 8.39 (d, J = 5.1 Hz, 2H, ArH), 8.06 (m, 6H, ArH), 7.89 (m, 2H, ArH), 7.71 (m, 4H, ArH), 7.47 (m, 2H, ArH), 7.34-7.19 (br, 12H, ArH), 4.16 (m, 4H, ArH), 2.00 (m, 2H, -CH-), 1.32-1.21 (br, 80H, CH2-), 0.85 (m, 12H, -CH3). 13C NMR (75 MHz, CDCl3)  (ppm): 163.34, 143.94, 140.54, 139.82, 139.09, 135.04, 134.24, 130.24, 129.57, 129.02, 127.87, 127.51, 125.93, 123.31, 122.37, 122.03, 120.17, 109.38, 44.68, 36.68, 31.84, 31.63, 30.02, 29.62, 29.28, 26.45, 22.60, 14.03. C108H128N4O4: C 83.89, H 8.34, N 3.62, found: C 83.71, H 8.24, N 3.75.

Synthesis of DCzPDI. Under an atmosphere of nitrogen, 2 (0.208 g, 0.18 mmol), 3 (0.329 g, 0.62 mmol), K2CO3 (0.280 g, 2.0 mmol) and Pd(PPh3)4 (0.045 g) were dissolved in THF/H2O (8 mL/2 mL). Then the mixture was refluxed for 36 h. After being cooled to room temperature, the solvent was evaporated under reduced pressure. The crude product was purified by a silica gel column using dichloromethane/petroleum ether (2:3) as an eluent to give DCzPDI as a purple-red solid (218 mg, 82.9 %). 1H NMR (300 MHz, CDCl3)  (ppm): 8.82 (s, 2H, ArH), 8.59 (d, J = 8.1 Hz, 2H, ArH ), 8.30 (d, J = 8.1 Hz, 2H, ArH), 8.12 (d, J = 7.8 Hz, 8H, ArH), 7.29 (s, 2H, ArH ), 7.46 (d, J = 8.1 Hz, 8H, ArH), 7.38 (t, J = 6.6 Hz, 6H, ArH), 7.31-7.28 (m, 8H, ArH), 4.17 (d, J = 6.6 Hz, 4H, ArH), 2.0 (s, 2H, -CH-), 1.35-1.20 (m, 72H, -CH2-), 0.84 (br, 12H, -CH3). 13C NMR (75 MHz, CDCl3)  (ppm): 163.28, 145.40, 141.20, 140.30, 139.06, 134.76, 134.33, 132.55, 130.41, 129.95, 129.19, 127.99, 126.23, 125.34, 123.66, ACS Paragon Plus Environment

17

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 18 of 26

122.75, 122.42, 120.64, 120.49, 109.36, 44.85, 36.77, 31.84, 31.65, 30.05, 29.79, 29.28, 26.47, 22.61, 14.04. Anal. Calcd for: C132H142N6O4: C 84.48, H 7.63, N 4.48, found: C 84.35, H 7.45, N 4.63. Synthesis of DCzPDI-NPs. DCzPDI-NPs were fabricated by using a modified nanoprecipitation procedure. Briefly, chloroform solution of DCzPDI (200 μL, 1 mg mL−1) and chloroform solution of F127 (240 μL, 10 mg mL−1) were added into a flask. The obtained mixture was then dried under vacuum in a rotary evaporator to remove the chloroform completely. After that, DI water (200 μL) was added and the flask was placed under sonication for several minutes. Finally, the aqueous dispersion of DCzPDINPs was obtained. Measurement of the 3PF of DCzPDI-NPs. The fluorescence spectrum of DCzPDI-NPs under threephoton excitations was recorded by a lab-built fluorescence measuring system in Zhejiang University. A 1550 nm fs laser (FLCPA-01C, Calmar Laser, 400 fs, 1 MHz) was adopted as the source. The laser beam from the light source was focused onto the cuvette containing DCzPDI-NPs solution in a cuvette via a lens (f = 50 mm). The excited fluorescence was collected perpendicularly using an objective lens (Olympus XLPlan N, 25×, NA=1.05, work distance = 2.0 mm), filtered using a 980 nm short-pass filter (Semrock), and then directed into the spectrometer (PG2000, Ideaoptics Instruments). Measurement of 3PA Cross Section. The three-photon absorption cross section (σ3) of DCzPDI-NPs was measured via the classical nonlinear transmissivity method in accordance with the reported literature.2 Cytotoxicity of DCzPDI-NPs. Cell Counting Kit-8 based cell viability assay was carried out to evaluate the metabolic activity of cells. HeLa cells were seeded in 96-well plates for 48 hours. Then, 200 L of fresh culture medium containing DCzPDI-NPs with various DCzPDI concentrations (0–2 mg/mL) was added to each well. After incubation for 24 hours the culture medium was removed and the cell well was washed three times with PBS. The cells we used firmly adhered to the bottom of the well, and the washing was performed carefully to avoid the loss of cells from the wells. At last, 200 L of culture medium containing CCK-8 (10%) was added to each well for 2 hours. Then the supernatant in each well ACS Paragon Plus Environment

18

Page 19 of 26 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

was taken out and its absorbance at 450 nm was measured with a microplate reader (Thermo, USA). Animals’ preparation. All the animal experiments were conducted according to requirements and guidelines of the Institutional Ethical Committee of Animal Experimentation of Zhejiang University. The animals were fed with clean water and standard laboratory chow, and their housing area was kept at 24 °C with a 12 h day/night cycle. Histology Analysis of DCzPDI-NPs. As the experimental group, mice were intravenously injected with DCzPDI-NPs (DCzPDI concentration 1.5 mg/mL, in 300 μL 1×PBS), and as the control group, mice were injected with only PBS (300 μL, 1×) solution. After 40 days, both of the experimental and control groups were sacrificed, and their major organs (lung, liver, spleen, kidney and heart) were resected through surgery. Tissue samples were then harvested and fixed in 4% paraformaldehyde overnight at 4 °C. After that, the tissue samples were embedded in paraffin, sectioned, and stained with hematoxylin and eosin (H&E). The histological sections were imaged under an inverted optical microscope with objective lenses of 40×magnifications at bright-field mode. Optical system for 3PF imaging. In order to get 3PF imaging of the brain vasculature of mice, an upright scanning microscope (Olympus, BX61W1-FV1200) equipped with a 1550 nm fs laser (FLCPA01C, Calmar Laser, 400 fs, 1 MHz) was adopted. After passing through a scan lens and a tube lens, the laser beam was focused onto the sample by a water-immersed microscope objective (XLPLN25XWMP2, Olympus, 25×, 1.05 NA). The imaging sample could be a glass capillary tube filled with an aqueous dispersion of DCzPDI-NPs or brain of a live mouse. 3PF signals were epi-collected with the same objective and then passed through a customized 1035 nm short-pass dichroic mirror and a 590 nm longpass filter (removing the excitation light and ambient noise). After that, the rest of fluorescence signals were collected using an internal photomultiplier tube of Olympus FV1200 via non-descanned detection (NDD). Pictures were collected every 5 m along the Z-axis and 3D imaging was reconstructed by Zscan stacks. ACS Paragon Plus Environment

19

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 20 of 26

ASSOCIATED CONTENT Supporting Information. The fluorescence and absorption spectra in different conditions, photostability and thermostability, TEM images and DLS number-weighted diameter, fluorescence delay of DCzPDINPs, and Figures on the characterizations of PDI derivatives are available free of charge via the Internet at http://pubs.acs.org. The authors declare no competing financial interest.

AUTHOR INFORMATION Corresponding Authors *E-mail: [email protected] (Z. Li) *E-mail: [email protected] (Q. Li) *E-mail: [email protected] (J. Qian) ORCID Zhen Li: 0000-0002-1512-1345 Jun Qian: 0000-0003-2131-3885 Author Contributions ǁ

L. Zong, H. Zhang and Y. Li contributed equally to this work.


20

Page 21 of 26 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

ACKNOWLEDGMENTS We are grateful to the National Natural Science Foundation of China (51673151, 51573140 and 21734007), Hubei Province (2017CFA002), the Fundamental Research Funds for the Central Universities (2042017kf0247 and 2042018kf0014) for financial support, and the Zhejiang Provincial Natural Science Foundation of China (LR17F050001).

REFERENCES (1) Wang, Y. L.; Chen, M.; Alifu, N.; Li, S. W.; Qin, W.; Qin, A. J.; Tang, B. Z.; Qian. J. AggregationInduced Emission Luminogen with Deep-Red Emission for Through-Skull Three-Photon Fluorescence Imaging of Mouse. ACS Nano 2017, 11, 10452–10461. (2) Qin, W.; Zhang, P. F.; Li, H.; Lam, J. W. Y., Cai, Y. J.; Kwok, R. T. K.; Qian, J.; Zheng, W.; Tang, B. Z. Ultrabright Red AIEgens for Two-Photon Vascular Imaging with High Resolution and Deep Penetration. Chem. Sci. 2018, 9, 2705–2710. (3) Li, S. J.; Li, C.-Y.; Li, Y. F.; Fei, J. J.; Wu, P.; Yang, B.; Ou-Yang, J.; Nie. S. X. Facile and Sensitive Near-Infrared Fluorescence Probe for the Detection of Endogenous Alkaline Phosphatase Activity In Vivo. Anal. Chem. 2017, 89, 6854–6860. (4) Sedgwick, A. C.; Gardiner, J. E.; Kim, G.; Yevglevskis, M.; Lloyd, M. D. A.; Jenkins, T. A.; Bull, S. D.; Yoon, J.; James. T. D. Long-Wavelength TCF-Based Fluorescence Probes for the Detection and Intracellular Imaging of Biological Thiols. Chem. Commun. 2018, 54, 4786–4789. (5) Hong, G.; Zou, Y.; Antaris, A. L.; Diao, S.; Wu, D.; Cheng, K.; Zhang, X.; Chen, C.; Liu, B.; He, Y.; Wu, J. Z.; Yuan, J.; Zhang, B.; Tao, Z.; Fukunaga, C.; Dai, H. Ultrafast Fluorescence Imaging In Vivo with Conjugated Polymer Fluorophores in the Second Near-Infrared Window. Nat. Commun. 2014, 5, 4206. (6) Horton, N. G.; Wang, K.; Kobat, D.; Clark, C. G.; Wise, F. W.; Schaffer, C. B.; Xu, C. In Vivo ThreePhoton Microscopy of Subcortical Structures Within an Intact Mouse Brain. Nat. Photonics 2013, 7, 205– 209. ACS Paragon Plus Environment

21

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 22 of 26

(7) Nilsson, G. E.; Tenland, T.; Oberg, P. A. Evaluation of a Laser Doppler Flowmeter for Measurement of Tissue Blood Flow. Ieee Eng. Med. Biol. 1980, 10, 597–604. (8) Haywood, J. R.; Shaffer, R. A.; Fastenow, C.; Fink, G. D.; Brody M. J. Regional Blood Flow Measurement with Pulsed Doppler Flowmeter in Conscious Rat. Am. J. Physiol-Heart C. 1981, 241, H273–H278. (9) Chen, Z.; Zhao, Y.; Srinivas, S. M.; Nelson, J. S.; Prakash N.; Frostig, R. D. Optical Doppler Tomography. Ieee J. Sel. Top. Quant. 1999, 5, 1134–1142. (10) Dunn, A. K.; Bolay, H.; Moskowitz, M. A.; Boas, D. A. Dynamic Imaging of Cerebral Blood Flow Using Laser Speckle. J. Cerebr. Blood F. Met. 2001, 21, 195–201. (11) Qian, J.; Zhu, Z.; Qin, A.; Qin, W.; Chu, L.; Cai, F.; Zhang, H.; Wu, Q.; Hu, R.; Tang, B. Z.; He, S. High-Order Non-Linear Optical Effects in Organic Luminogens with Aggregation-Induced Emission. Adv. Mater. 2015, 27, 2332–2339. (12) Chen, X.; Liu, Z.; Li, R.; Shan, C.; Zeng, Z.; Xue, B.; Yuan, W.; Mo, C.; Xi, P.; Wu, C.; Sun, Y.; Multicolor Super-Resolution Fluorescence Microscopy with Blue and Carmine Small Photoblinking Polymer Dots. ACS Nano 2017, 11, 8084−8091. (13) Dimitrakopoulos, C. D.; Malenfant, P. R. L.; Organic Thin Film Transistors for Large Area Electronics. Adv. Mater. 2002, 14, 99–117. (14) Qin, W.; Li, K.; Feng, G.; Li, M.; Yang, Z.; Liu, B.; Tang, B. Z. Bright and Photostable Organic Fluorescent Dots with Aggregation-Induced Emission Characteristics for Noninvasive Long-Term Cell Imaging. Adv. Funct. Mater. 2014, 24, 635–643. (15) Yan, Q.; Zhou, Y.; Zheng, Y.; Peiand, J.; Zhao, D. Towards Rational Design of Organic Electron Acceptors for Photovoltaics: A Study Based on Perylenediimide Derivatives. Chem. Sci. 2013, 4, 4389– 4394. (16) Zhan, X. J.; Zhang, J.; Tang, S.; Lin, Y. X.; Zhao, M.; Yang, J.; Zhang, H. L.; Peng, Q.; Yu, G.; Li, Z. Pyrene Fused Perylene Diimides: Synthesis, Characterization and Applications in Organic Field-Effect Transistors and Optical Limiting with High Performance. Chem. Commun. 2015, 51, 7156–7159. (17) Sun, D.; Meng, D.; Cai, Y. H.; Fan, B. B.; Li, Y.; Jiang, W.; Huo, L. J.; Sun, Y. M.; Wang, Z. H. NonFullerene-Acceptor-Based Bulk-Heterojunction Organic Solar Cells with Efficiency Over 7%. J. Am. ACS Paragon Plus Environment

22

Page 23 of 26 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

Chem. Soc. 2015, 137, 11156–11162. (18) Sonar, P.; Lim, J. P. F.; Chan, K. L. Organic Non-Fullerene Acceptors for Organic Photovoltaics. Energy Environ. Sci. 2011, 4, 1558–1574. (19) Zong, L. Y.; Gong, Y. B.; Yu, Y.; Xie, Y. J.; Xie, G. H.; Peng, Q.; Li, Q. Q.; Li, Z. New Perylene Diimide Derivatives: Stable Red Emission, Adjustable Property from ACQ to AIE, and Good Device Performance with an EQE Value of 4.93%. Sci. Bull. 2018, 63, 108–116. (20) Wu, J. l.; Huang, W. K; Chang, Y. C.; Tsai, B. C.; Hsiao, Y. C.; Chang, C. Y.; Chen, C. T.; Chen, C. T. Simple Mono-Halogenated Perylene Diimides as Non-Fullerene Electron Transporting Materials in Inverted Perovskite Solar Cells with ZnO Nanoparticle Cathode Buffer Layers. J. Mater. Chem. A 2017, 5, 12811–12821. (21) Wang, J. l.; Peng, J. J.; Liu, X. Y.; Liang, Z. Q. Efficient and Stable Ternary Organic Solar Cells Based on Two Planar Nonfullerene Acceptors with Tunable Crystallinity and Phase Miscibility. ACS Appl. Mater. Interfaces, 2017, 9, 20704–20710. (22) Würthner, F.; Saha-Möller, C. R.; Fimmel, B.; Ogi, S.; Leowanawat, P.; Schmidt, D. Perylene Bisimide Dye Assemblies as Archetype Functional Supramolecular Materials. Chem. Rev. 2016, 116, 962−1052. (23) Wolfbeis, O. S. An Overview of Nanoparticles Commonly Used in Fluorescent Bioimaging. Chem. Soc. Rev. 2015, 44, 4743–4768. (24) Zhang, X.; Zhang, X.; Wang, S.; Liu, M.; Tao, L.; Wei, Y. Surfactant Modification of AggregationInduced Emission Material as Biocompatible Nanoparticles: Facile Preparation and Cell Imaging. Nanoscale 2013, 5, 147–150. (25) Zhang, X.; Wang, K.; Liu, M.; Zhang, X.; Tao, L.; Chen, Y.; Wei, Y. Polymeric AIE-Based Nanoprobes for Biomedical Applications: Recent Advances and Perspectives. Nanoscale 2015, 7, 11486– 11508. (26) Wan, Q.; Jiang, R.; Mao, L.; Xu, D.; Zeng, G.; Shi, Y.; Deng, F.; Liu, M.; Zhang, X.; Wei, Y. A Powerful ‘‘One-Pot’’ Tool for Fabrication of AIE-Active Luminescent Organic Nanoparticles Through the Combination of RAFT Polymerization and Multicomponent Reactions. Mater. Chem. Front. 2017, 1, 1051–1058.


23

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 24 of 26

(27) Yang, J.; Li, L.; Yu, Y.; Ren, Z. C.; Peng, Q.; Ye, S. H.; Li, Q. Q.; Li, Z. Blue Pyrene-Based AIEgens: Inhibited Intermolecular – Stacking Through the Introduction of Substituents with Controllable Intramolecular Conjugation, and High External Quantum Efficiencies Up to 3.46% in Non-Doped OLEDs. Mater. Chem. Front. 2017, 1, 91–99. (28) Li, H. Y.; Yang, L. Y.; Tang, R. L.; Hou, Y. Q.; Yang, Y. Z.; Wang, H.; Han, H. W.; Qin, J. G.; Li, Q. Q.; Li, Z. Organic Dyes Incorporating N-Functionalized Pyrrole as Conjugated Bridge for Dye-Sensitized Solar Cells: Convenient Synthesis, Additional Withdrawing Group on the π-Bridge and the Suppressed Aggregation. Dyes Pigm. 2013, 79, 863–870. (29) Li, H. Y.; Hou, Y. Q.; Yang, Y. Z.; Tang, R. L.; Chen, J. N.; Wang, H.; Han, H. W.; Peng, T. Y.; Li, Q. Q.; Li, Z. Attempt to Improve the Performance of Pyrrole-Containing Dyes in Dye Sensitized Solar Cells by Adjusting Isolation Groups. ACS Appl. Mater. Interfaces 2013, 5, 12469–12477. (30) Li, H. Y.; Yang, Y. Z.; Hou, Y. Q.; Tang, R. L.; Duan, T. N.; Chen, J. N.; Wang, H.; Han, H. W.; Peng, T. Y.; Chen, X. G.; Li, Q. Q.; Li, Z. Organic Sensitizers Featuring 9,10-Diaryl-Substituted Anthracene Unit. ACS Sustainable Chem. Eng. 2014, 2, 1776–1784. (31) Shi, J.; Huang, J.; Tang, R. L.; Chai, Z. F.; Hua, J. L.; Qin, J. G.; Li, Q. Q.; Li, Z. Efficient MetalFree Organic Sensitizers Containing Tetraphenylethylene Moieties in the Donor Part for Dye-Sensitized Solar Cells. Eur. J. Org. Chem. 2012, 27, 5248–5255. (32) Li, Q. Q.; Lu, L. L.; Zhong, C.; Huang, J.; Huang, Q.; Shi, J.; Jin, X. B.; Peng, T. Y.; Qin, J. G.; Li, Z. New Pyrrole-Based Organic Dyes for Dye-Sensitized Solar Cells: Convenient Syntheses and High Efficiency. Chem. Eur. J. 2009, 15, 9664–9668. (33) Tang, R. L.; Zhou, S. M.; Cheng, Z. Y.; Yu, G.; Peng, Q.; Zeng, H. Y.; Guo, G. C.; Li, Q. Q.; Li, Z. Janus Second-Order Nonlinear Optical Dendrimers: Their Controllable Molecular Topology and Corresponding Largely Enhanced Performance. Chem. Sci. 2017, 8, 340–347. (34) Qin, W.; Ding, D.; Liu, J.; Yuan, W. Z.; Hu, Y.; Liu, B.; Tang, B. Z. Biocompatible Nanoparticles with Aggregation-Induced Emission Characteristics as Far-Red/Near-Infrared Fluorescent Bioprobes for In Vitro and In Vivo Imaging Applications. Adv. Funct. Mater. 2012, 22, 771–779. (35) Liang, J.; Tang, B. Z.; Liu, B. Specific Light-Up Bioprobes Based on AIEgen Conjugates. Chem. Soc. Rev. 2015, 44, 2798–2811. (36) Mei, J.; Leung, N. L. C.; Kwok, R. T. K.; Lam, J. W. Y.; Tang, B. Z. Aggregation-Induced Emission: ACS Paragon Plus Environment

24

Page 25 of 26 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

Together We Shine, United We Soar! Chem. Rev. 2015, 115, 11718–11940. (37) Chiang, C. L.; Wu, M. F.; Dai, D. C.; Wen, Y. S.; Wang, J. K.; Chen, C. T. Red-Emitting Fluorenes as Efficient Emitting Hosts for Non-Doped, Organic Red-Light-Emitting Diodes. Adv. Funct. Mater., 2005, 15, 231–238. (38) Hong, Y.; Lam, J. W. Y.; Tang, B. Z. Aggregation-Induced Emission: Phenomenon, Mechanism and Applications. Chem. Commun. 2009, 45, 4332–4353. (39) Xie, N.-H.; Li, C.; Liu, J.-X.; Gong, W.-L.; Tang, B. Z.; Li, G. G.; Zhu, M. Q. The Synthesis and Aggregation-Induced Near-Infrared Emission of Terrylenediimide-Tetraphenylethene Dyads. Chem. Commun. 2016, 52, 5808–5811. (40) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, Jr. J. A.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H. et. al. Gaussian, Inc., Pittsburgh, PA, 2009. (41) Wang, Y. L.; Hu, R. R.; Xi, W.; Cai, F. H.; Wang, S. W.; Zhu, Z. F.; Bai, R. P.; Qian, J. Red Emissive AIE Nanodots with High Two-Photon Absorption Efficiency at 1040 nm for Deep-Tissue In Vivo Imaging. Biomed. Opt. Express 2015, 6, 3783–3794. (42) He, G. S.; Tan, L.-S.; Zheng, Q. D.; Prasad, P. N. Multiphoton Absorbing Materials: Molecular Designs, Characterizations, and Applications. Chem. Rev. 2008, 108, 1245–1330. (43) Xing, G.; Chakrabortty, S.; Ngiam, S. W.; Chan, Y.; Sum, T. C. Three-Photon Absorption in Seeded CdSe/Cds Nanorod Hetero-Structures. J. Phys. Chem. C 2011, 115, 17711–17716. (44) Zhou, E.; Cong, J.; Wei, Q.; Tajima, K.; Yang, C.; Hashimoto, K. All-Polymer Solar Cells from Perylene Diimide Based Copolymers: Material Design and Phase Separation Control. Angew. Chem. Int. Ed. 2011, 50, 2799–2803.


25

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 26 of 26

Insert Table of Contents Graphic


26

Tunable Aggregation-Induced Emission Nanoparticles by Varying

Recommend Documents