Twisted Intramolecular Charge Transfer—Aggregation-Induced Emission Fluorogen with Polymer Encapsulation-Enhanced Near-Infrared Emission for Bioimaging

Abstract

Open AccessCCS ChemistryRESEARCH ARTICLE1 Mar 2021Twisted Intramolecular Charge Transfer—Aggregation-Induced Emission Fluorogen with Polymer Encapsulation-Enhanced Near-Infrared Emission for Bioimaging Lingchen Meng†, Xibo Ma†, Shan Jiang, Song Zhang, Zhiyuan Wu, Bin Xu, Zhen Lei, Leijing Liu and Wenjing Tian Lingchen Meng† State Key Laboratory of Supramolecular Structure and Materials, Department of Chemistry, Jilin University, Changchun 130012 , Xibo Ma† CBSR&NLPR, Institute of Automation, Chinese Academy of Sciences, Beijing 100049 School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing 100049 , Shan Jiang State Key Laboratory of Supramolecular Structure and Materials, Department of Chemistry, Jilin University, Changchun 130012 , Song Zhang State Key Laboratory of Supramolecular Structure and Materials, Department of Chemistry, Jilin University, Changchun 130012 , Zhiyuan Wu State Key Laboratory of Supramolecular Structure and Materials, Department of Chemistry, Jilin University, Changchun 130012 , Bin Xu State Key Laboratory of Supramolecular Structure and Materials, Department of Chemistry, Jilin University, Changchun 130012 , Zhen Lei CBSR&NLPR, Institute of Automation, Chinese Academy of Sciences, Beijing 100049 School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing 100049 , Leijing Liu *Corresponding authors: E-mail Address: [email protected] E-mail Address: [email protected] State Key Laboratory of Supramolecular Structure and Materials, Department of Chemistry, Jilin University, Changchun 130012 and Wenjing Tian *Corresponding authors: E-mail Address: [email protected] E-mail Address: [email protected] State Key Laboratory of Supramolecular Structure and Materials, Department of Chemistry, Jilin University, Changchun 130012 https://doi.org/10.31635/ccschem.020.202000420 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesTrack Citations ShareFacebookTwitterLinked InEmail Fluorescence probes with strong near-infrared (NIR) emission and water solubility are considered useful visualization tools for localization marking as well as investigating cell migration and transplantation. Here, we designed and synthesized a new donor–π–acceptor (D–π–A) fluorogen, 2-(4-[(E)-4-(diphenylamino)styryl]phenyl)-3-(4′-[1,2,2-triphenylvinyl]-[1,1′-biphenyl]-4-yl) fumaronitrile (TB-TPE). TB-TPE exhibits twisted intramolecular charge transfer (TICT) and aggregation-induced emission (AIE) in the NIR region, with an emission peak at 714 nm and a fluorescence quantum yield (Qy) of 6.6% in the solid state. By encapsulating TB-TPE with polystyrene–polyethylene glycol (PS-PEG), water-soluble TB-TPE-PS-PEG nanoparticles (TP NPs) are fabricated, which display polymer encapsulation-enhanced emission with a Qy of 46.5% due to the strong restriction effect on the TICT process and the destruction of H aggregation for TB-TPE by the polymer matrix. Au-coated Fe3O4 (Fe3O4@Au) nanocrystals were then embedded in the TP NPs to form highly fluorescent TB-TPE-Fe3O4-Au-PS-PEG nanoparticles (TFAP NPs) with a Qy of 39.7%. Our demonstration of successful cellular imaging of TP NPs for Hep-G2 cells and multimodality imaging of TFAP NPs in mouse liver tumors indicates that polymer-encapsulated TB-TPE offers great prospects as a multifunctional fluorescence probe for bioimaging. Download figure Download PowerPoint Introduction Ultrahigh-sensitive, low-cost, noninvasive, on-site, and real-time fluorescence molecular imaging (FMI) has attracted considerable interest in biological and preclinical studies for the monitoring of biosamples and the acquisition of information on biological structures.1–3 Organic fluorescent dyes have been developed and extensively utilized in FMI because of their good biocompatibility and low toxicity.4,5 One issue in the application of conventional organic molecular probes is the aggregation-caused quenching (ACQ) effect in the aggregate state, due to a planar aromatic conformation.6,7 Exploiting twisted structural organic molecular probes will avoid the ACQ problem because the twisted molecular conformation can reduce intermolecular π–π interactions and thus lead to aggregation-induced emission (AIE) in the aggregate state.8–13 Water-soluble AIE luminogens (AIEgens) have attracted much attention because they are beneficial for biological probing and imaging. In general, encapsulation media, such as inorganic substrates of silica,14,15 organic substrates of surfactants,16–18 and amphiphilic copolymers,19–21 are used as matrices to improve the water solubility of lipophilic AIE dyes. AIE dyes encapsulated by polymer matrices are widely used in FMI due to their good biocompatibility, photostability, and water solubility; polymer-encapsulated AIEgens with a far-red/near-infrared (NIR) wavelength range are especially attractive because of their superior performance due to high imaging penetration depth and enhanced signal-to-noise ratio.22–25 However, NIR-emissive AIEgens with polymer-coated twisted donor (D)–acceptor (A) structures may cause undesirable twisted intramolecular charge transfer (TICT) effects in polar solvents, which promote an efficient channel for the excited state to decay nonradiatively, thereby leading to a substantial decrease in the fluorescence quantum yield (Qy).26–30 For example, Li et al.31 developed an NIR-emissive TPETPAFN (2,3-bis(4-(phenyl(4-(1,2,2-triphenylvinyl) phenylamino) phenyl) fumaronitrile) AIEgen with a high Qy in the solid state (Qysolid) of 52.5%, but when TPETPAFN was embedded in a DSPE-PEG (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly (ethylene glycol)) polymer matrix to prepare AIE nanoparticles, the fluorescence Qy decreased to 24%. Likewise, Zong et al.32 synthesized a perylene diimide fluorophore (Qysolid: 12.3%) with AIE and TICT features for three-photon fluorescence bioimaging of brain blood vessels and found that the Qy of nanoparticles prepared using Pluronic F-127 as the matrix decreased to 2.37%. Che et al.33 prepared efficient NIR-emissive nanoparticles for long-term cell tracing by coating an AIE-active BODIPY (Boron Dipyrromethene)-derivative with DSPE-PEG2000 amphiphilic polymer, whose Qy (26%) is lower than that of BODIPY AIEgen (30%). As reported in the previous studies, the fluorescence efficiency of nanoparticles prepared by polymer encapsulating NIR-emissive AIE dye with the TICT feature is generally lower than that of contained fluorescent dyes in the solid state. Herein, to acquire an NIR-emissive fluorescent probe, we chose an electron-donating triphenylamine group as the donor, an electron-accepting fumaric acid nitrile unit as the acceptor, and a vinyl bond as the π-bridge to synthesize 2-(4-[(E)-4-(diphenylamino)styryl]phenyl)-3-(4′-[1,2,2-triphenylvinyl]-[1,1′-biphenyl]-4yl) fumaronitrile (TB-TPE). The introduction of AIE active tetraphenylethylene with twisted conformation increased the steric hindrance, leading to enhanced fluorescence emission of the molecule. TB-TPE possessed TICT and AIE as well as polymer encapsulation-enhanced emission features. The Qy of TB-TPE was 6.6% in the solid state, while that of nanoparticles prepared by encapsulating TB-TPE with polystyrene–polyethylene glycol (PS-PEG) increased to 46.5%, due to the restriction of the TICT process and the destruction of H-type aggregation for TB-TPE in the aggregate state. The Qy remained as high as 39.7% even when Au-coated Fe3O4 (Fe3O4@Au) nanocrystals were embedded into PS-PEG-encapsulated nanoparticles. The cellular imaging of Hep-G2 cells and the multimodality imaging of mouse liver tumors demonstrated here indicate that nanoparticles prepared by polymer-encapsulating TB-TPE hold great potential in biological fluorescence imaging. Experimental Methods Materials All reagents and starting materials are commercially available and were used without further purification, unless otherwise stated. Sodium methanolate, 4-bromophenylacetonitrile, Ph3P+CH3Br−, t-BuOK, 1-(4-phenylboronic acid pinacol ester)-1,2,2-triphenylethene, AgCO3, tetrakis(triphenylphosphine)palladium [Pd(PPh3)4], iodine, 4-(diphenylamino)-benzaldehyde, and Pd(OAc)2 were purchased from Aladdin Reagent Co. (Shanghai, China). Tetrahydrofuran (THF), methanol, diethyl ether, and toluene were purchased from Energy Chemical Co. (Shanghai, China). PS-PEG was purchased from RUIXIBIO Co. (Xi'an, Shanxi, China). The ultrapure deionized water used had a resistivity of 18.2 MΩ·cm. Instrumentations 1H NMR spectra were acquired in dimethyl sulfoxide-d6 on a Bruker AVANCE III 500-MHz spectrometer and mass spectra on a Bruker Autoflex Speed TOF. Absorption spectra were obtained on a SPECORD 210 PLUS UV–Vis spectrophotometer. Transmission electron microscopy (TEM) images were obtained using a JEM-2100F system. Fluorescence lifetime and Qy measurements were conducted on an Edinburgh FLS920 spectrometer. Cell fluorescence images were obtained using LEICA confocal laser scanning microscopy (CLSM) (TCS SP8 STED 3X), and hydrodynamic size distribution was measured with a Malvern Zetasizer Nano ZS apparatus at 37 °C. Fluorescence imaging in vivo was performed using an IVIS spectrum imaging system. Magnetic resonance imaging (MRI) was performed using the Bruker BioSpec 70/20 USR MRI, and Computerized Tomography (CT) imaging was performed using a PE Quantum FX device. Synthesis of TB-TPE TB molecules were prepared per the previous literature synthesis.34 Under continuous N2 flow, 100 mL toluene, 10 mL THF, and 10 mL water were added to a mixture of TB (1.16 g, 2 mmol), Pd(PPh3)4 (100 mg, 0.1 mmol), pinacol ester-1,2,2-triphenylethene (2.8 g, 3 mmol), and potassium carbonate (4.14 g, 30 mmol) in a 250-mL Shrek tube eggplant-shaped reaction bottle. The solution was heated to reflux over 12 h with stirring and then cooled to room temperature and extracted three times with dichloromethane. The red organic phase of the solution was collected; the crude product was purified by rapid ultraperformance liquid chromatography using dichloromethane:n-hexane (v/v = 5∶1) as eluent to furnish a red solid. Yield: 70%. 1H NMR (500 MHz, DMSO-d6, δ): 7.88 (d, J = 21.6 Hz, 6H), 7.81 (d, J = 8.5 Hz, 2H), 7.62 (d, J = 8.3 Hz, 2H), 7.57 (d, J = 8.6 Hz, 2H), 7.42 (d, J = 16.3 Hz, 1H), 7.34 (t, J = 7.8 Hz, 4H), 7.25–6.95 (m, 26 H). 13C NMR (126 MHz, CDCl3, δ): 148.15, 147.32, 144.06, 143.85, 143.54, 141.61, 141.31, 140.21, 137.03, 132.02, 131.37, 130.87, 130.38, 129.35, 129.16, 127.80, 127.65, 127.43, 126.77, 126.65, 126.30, 125.12, 124.80, 124.36, 123.45, 123.38, 123.00, 117.05, 116.89. High-resolution mass spectrometry (HRMS) (matrix-assisted laser desorption/ionization time-of-flight [MALDI-TOF]) (m/z): 828.261. Single-crystal structure X-ray crystallographic diffraction intensity data for TB-TPE were collected on a Rigaku RAXIS-PRID diffractometer with graphite-monochromator Mo/Cu Kα radiation. The structure was solved with direct methods using the SHELXTL and Olex2 1.2 programs and refined with least-squares methods. The Cambridge Crystallographic Data Centre (CCDC) number for TB-TPE is 2010997.35,36 Computational methods Geometry optimizations for TB-TPE were acquired using time-dependent density functional theory (TDDFT) calculations with the CAM-B3LYP functional. Solvent effects in THF solution were considered through a solvation model based on density (SMD).37–39 [email protected] nanoparticles for cellular imaging One million Hep-G2 cells were incubated with [email protected] nanoparticles (TP NPs) and Hoechst 33258 for 3 h in a confocal dish containing 1 mL Dulbecco's modified Eagle's medium (DMEM) culture medium. After three washes with phosphate-buffered saline (PBS) solution, 1 mL PBS solution was added to the confocal dish and immediately followed by CLSM imaging. The experimental procedures regarding cell cytotoxicity are described in detail in the Supporting Information. TB-TPE&Fe3O4@[email protected] nanoparticles for FMI/MRI/CT multimodal imaging All animal experiments were carried out following the guidelines of the institutional ethics committee of animal experimentation of Peking University (Beijing, China). Hep-G2 cells incubated with TB-TPE&Fe3O4@[email protected] nanoparticles (TFAP NPs) were administered through subcutaneous injection into the abdomen of 6-week-old male BALB/c mice. In vivo imaging of the mice was conducted using an IVIS instrument with laser excitation at 465 nm. The fluorescence signals were filtered using a 660-nm filter. MRI was conducted using a Bruker 7.0T small-animal MRI system equipped with a commercial coil with the following scan parameters: Repetition Time/Echo Time = 3000/40 ms, 1-mm slice thickness, Field of View 35 × 35 mm2, 200 × 200 matrix. CT imaging in vivo was conducted using a PE Quantum FX system and processed with Analyze 11.0 software. Results and Discussion Synthesis and characterization of TB-TPE TB-TPE was synthesized via a typical Suzuki coupling reaction using TB and [4-(1,2,2-triphenylethenyl)phenyl]boronic acid; the synthesis procedure is depicted in Figure 1a. The molecular structure of the TB-TPE compound was confirmed by 1H NMR and 13C NMR spectroscopy and further validated by HRMS ( Supporting Information Figures S1–S3). The normalized photoluminescence (PL) spectra of TB-TPE in n-hexane and THF solution are shown in Supporting Information Figure S4, exhibiting a significant red shift in emissions from 577 to 784 nm with the increase in solvent polarity. To fully understand the solvatochromic behavior of TB-TPE, we assessed the photophysical properties of TB-TPE in mixed solvents of THF/n-hexane, including absorption and emission maximum, fluorescence Qy, lifetime, and radiative (kr) and nonradiative (knr) decay rates; the parameters are listed in Supporting Information Table S1. The emission spectra of TB-TPE in solvent mixtures with different THF fractions (fTHF) (Figure 1b) show that increasing the solvent polarity considerably reduced the PL intensity of the TB-TPE solution, decreased the Qy significantly from 92.3% to 0.8%, and red-shifted the emission maximum (Figure 1c). We further investigated the solvent effect on the emission characteristics using the Lippert–Mataga equation by assessing the relationship between the solvent polarity parameter (Δf) and the Stokes shift of the absorption and emission maximum. The linearity of the Lippert–Mataga plot in Supporting Information Figure S5a suggests a strong intramolecular charge transfer (ICT) process during the TB-TPE excitation process, thereby leading to a large Stokes shift of TB-TPE in polar solvents.40–42 When the fTHF in the mixed solvents increased from 0% to 100%, the knr of the TB-TPE solution gradually increased from 3.02 × 107 to 7.43 × 108 s−1, while kr decreased from 3.64 × 108 to 2.96 × 107 ( Supporting Information Figure S5b). This indicates that high solvent polarity promoted the nonradiative relaxation process, resulting in a sharp decline in fluorescence Qy and in almost complete loss of fluorescence. Figure 1 | (a) Synthetic procedures and chemical structure of TB-TPE; (b) PL spectra; (c) fluorescence Qy in THF/n-hexane solvent mixture with different fTHF; (d) PL spectra of TB-TPE in THF/water mixtures with different water fractions (fw), and (e) plots of PL maximum and relative PL intensity (I/I0) versus the composition of the THF/water mixture of TB-TPE, where I0 was the PL intensity at 50%. Download figure Download PowerPoint The PL spectra of TB-TPE in water/THF solution with different water fractions (fw) were measured to investigate the photophysical properties of TB-TPE molecules in the aggregate state. As shown in Figures 1d and 1e, when the fw increased from 0% to 50%, the PL intensity of TB-TPE gradually decreased, accompanied by a red-shifted emission due to an enhanced ICT effect in the presence of the more polar solvent (water) in the surrounding environment. We recorded a significant (57-fold) enhancement in the fluorescence intensity, with a blue shift in emissions from 807 to 691 nm, when fw increased from 50% to 99%, indicating the dominant role of the AIE over the ICT effect. Concurrently, TB-TPE powder displayed an obvious gain in Qy (6.6%) and a blue-shifted emission (709 nm) peak compared with the TB-TPE in THF solution (Qy of 0.8% and emission peak at 771 nm) ( Supporting Information Figure S6). To investigate the AIE properties of TB-TPE, we studied the viscosity dependence of TB-TPE monomer emissions in a mixture of glycerol and ethanol with varied volume fractions ( Supporting Information Figure S7a). When viscosity increased, fluorescence Qy of TB-TPE likewise increased ( Supporting Information Figure S7b). Additionally, as the glycerol/ethanol mixture became more viscous, the TB-TPE kr increased and knr decreased ( Supporting Information Figure S7c). These results suggest that the AIE properties of TB-TPE in the aggregate state originated from a restricted intramolecular motion (RIM) mechanism, which could suppress the molecular motion and effectively improve the fluorescence probe efficiency. Construction of highly efficient fluorescent TP NPs for cellular imaging TB-TPE was encapsulated by PS-PEG to form water-soluble TP NPs as a potential candidate for bioimaging contrast agents. We investigated the influence of different concentrations of PS-PEG on the fluorescence performance of TB-TPE. Figure 2 shows a gradual blue shift in the PL maximum of TP NPs (Figure 2a) and an obvious enhancement in the fluorescent Qy of TP NPs with an increase in the concentration of PS-PEG (Figure 2b). When the concentration of PS-PEG reached 10 μg/mL, the highest fluorescence Qy (46.5%) was observed, seven times higher than that of TB-TPE powder, followed by a slight abatement in fluorescence Qy with the sequential increase in PS-PEG concentration. When the concentration of PS-PEG approached 20 μg/mL, the self-absorption of excessive amphiphilic polymers in fluorescence nanoparticles blocked the excitation light and the encapsulated TB-TPE inside nanoparticles were not effectively excited, resulting in a slight decline in the fluorescence Qy of TP NPs.43,44 Figure 2 | (a) PL spectra and (b) fluorescence Qy of TP NPs with different concentration of PS-PEG. Download figure Download PowerPoint To understand the unique polymer encapsulation-enhanced emission properties of TP NPs, we investigated and compared TB-TPE as a solution and in crystal. The photophysical properties of TB-TPE in THF solution, in crystal form, and in TP NPs are depicted in Table 1. We found that TB-TPE is nearly nonemissive in THF solution, with the lowest luminous efficiency performance (i.e., a Qy of 0.8%) of the three. To gain further insight into this photophysical behavior of TB-TPE in polar solvent, we computationally simulated the ground state and the excited state conformation of TB-TPE in THF solution using TDDFT (Figure 3a). The optimized ground state conformation is characterized by a highly planar dicyanoethylene core with a dihedral angle of 2.3°, and the corresponding excited state conformation is more twisted, with a large dihedral angle of 55.10°. The calculation shows that TB-TPE molecules in polar solvent undergo a molecular geometry change from a near-planar configuration in the ground state to a nonplanar (twisted) configuration in the excited state to form the TICT state, thereby promoting the nonradiative relaxation process with significantly increased knr and resulting in nearly nonemissive fluorescence.45–47 Furthermore, the emission spectra of TB-TPE in THF solution were obtained at various temperatures from 77 to 273 K. As shown in Figure 3b, TB-TPE exhibits a strong orange emission at 77 K because the TICT process is restricted in the THF solution at low temperatures. As temperatures rise, the PL intensity of TB-TPE gradually decreases and the emission is red-shifted and broadened because the TB-TPE molecules have undergone a transition from a restricted intramolecular rotation to a free rotation, thereby leading to the promotion of the TICT effect.48–50 Table 1 | Photophysical Parameters of TB-TPE in THF Solution, TB-TPE Crystals, and TP NPs λem,max (nm) τ (ns) Φ kr knr TB-TPE in THF solution TB-TPE crystal TP NPs Figure 3 | (a) The optimized geometry of TB-TPE in the ground state and the excited state in THF (b) PL spectra of TB-TPE in THF solution 1 × at K. Download figure Download PowerPoint We then investigated the performance of TB-TPE in crystal Single-crystal TB-TPE was obtained by solvent in mixed solution Figure The powder X-ray diffraction of the of TB-TPE show sharp and indicating good structures ( Supporting Information Figure The Qy of TB-TPE increased to in the crystal state from 0.8% in THF solution, with kr increasing from × to × is that the Qy of crystal TB-TPE was significantly reduced compared with that of TB-TPE this to further the intermolecular interactions and molecular of TB-TPE in the state. intermolecular interactions such as and and were found in the crystal Figure The crystal of TB-TPE the of H-type aggregation in the crystal which in a lower Qy in the aggregate state (Figure the intermolecular interactions of TB-TPE in the aggregate state may the molecular conformation and intramolecular which are beneficial to the the of TB-TPE in the aggregate state Qy for further Figure | (a) Fluorescence (b) intermolecular and (c) of TB-TPE crystal. Download figure Download PowerPoint TP NPs in which TB-TPE was encapsulated by a polymer matrix the highest fluorescence compared with the TB-TPE solution and the crystal We found that in TP NPs, the nonradiative transition process of TB-TPE was which fluorescence emission through and to the in knr × and the highest increase in kr × on between TB-TPE in THF solution and crystal TB-TPE, we that the polymer matrix of TB-TPE a role in the enhanced Qy of TB-TPE in to previous studies, dyes encapsulated by amphiphilic can the of the via we a molecular to investigate the between TB-TPE and the polymer using as a model system. As shown in Figure the a and TB-TPE molecules are into the based on molecular (Figure Our results indicate that the matrix not a for the encapsulated dye to the TICT process but the dye to H-type aggregation in the aggregate state, resulting in significant enhancement in fluorescence efficiency. This the Qy of polymer-encapsulated TB-TPE is more than seven times higher than that of TB-TPE Figure | (a) images the lowest conformation of indicates and indicates polar (b) model for Download figure Download PowerPoint of their good water solubility and highly efficient TP NPs can used for cellular imaging. We obtained fluorescence images of Hep-G2 cells with CLSM with TP NPs for 3 was conducted to the Hep-G2 cells of TP NPs ( Supporting Information Figure in the red channel excitation by a laser light are shown in Supporting Information Figure indicating that TP NPs the cell and the cell Our cytotoxicity experiments indicate good cellular biocompatibility of TP NPs Supporting Information Figure Construction of efficient fluorescence TFAP NPs for FMI/MRI/CT multimodal imaging imaging probes were prepared by TB-TPE NIR dye and into a PS-PEG polymer matrix to form TFAP NPs, following a ( Supporting Information Figure Under TFAP NPs displayed strong red emission a maximum at nm) ( Supporting Information Figure a high Qy and a size distribution nm) ( Supporting Information Figure The application of TFAP multimodal probes for FMI/MRI/CT imaging was demonstrated by subcutaneous liver imaging. TFAP NPs Hep-G2 cells into a as shown in Figure a strong fluorescence was fluorescence images of mice were and their information could Figure In vivo MRI results (Figure were compared with the contrast MRI of mice without TFAP NPs injection ( Supporting Information Figure images of mice by TFAP NPs enhanced in the significant contrast is in the CT in Figure These results show that TFAP NPs are multimodal and suggest TFAP NPs are useful multimodal imaging with good depth penetration and Figure | (a) in vivo fluorescence images from to (b) (c) fluorescence and (d) CT of the mouse with 1 × of NPs Hep-G2 Download figure Download PowerPoint We designed and synthesized a NIR-emissive structure fluorescent probe TB-TPE with TICT and AIE TP NPs were prepared by encapsulating TB-TPE with a PS-PEG polymer matrix and polymer encapsulation-enhanced The fluorescence Qy (46.5%) was seven times higher than that of TB-TPE powder (6.6%) due to the between TB-TPE molecules and the PS-PEG polymer matrix that the TICT process in polar solvent and the H-type aggregation in the aggregate state of TB-TPE. The Qy remained as high as 39.7% even when TB-TPE and nanocrystals were into PS-PEG to form TFAP The good performance of the TP NPs in cellular imaging of Hep-G2 cells and in multimodality imaging of mouse liver tumors indicates that a based on polymer encapsulation-enhanced emission great potential for the application of AIEgens in biological fluorescence imaging. Supporting Information Supporting Information is of The of interest regarding the of this Information This was by the of and for of Jilin and the of Jilin 1. in the of of in and with Quantum for

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