ZnCl2 Enabled Synthesis of Highly Crystalline and Emissive Carbon Dots with Exceptional Capability to Generate O2⋅–

Abstract

•Crystalline and emissive carbon dots•Exceptional capability to generate O2⋅–•Outstanding photodynamic therapy and photocatalysis Carbon dots (CDs) are emerging as one of the most popular subsets of environmentally friendly nanomaterials for a broad scope of applications. However, their preparation is still thwarted by harsh reaction conditions as well as tedious multistep treatments. This work reports the first synthesis of highly crystalline and emissive CDs via an ionothermal method in organic solvents and provides an effective approach to large-scale production of luminescent CDs from various precursors under mild conditions. Strikingly, the resulting CDs exhibit excellent capability to photogenerate superoxide radical anion (O2⋅–), thus exemplifying preliminary applications both in photodynamic therapy and photocatalytic reactions. It is anticipated that the research presented here may pave a new avenue for the synthesis of carbon-based materials for advanced applications in the future. Highly crystalline and emissive carbon dots (CDs) are firstly synthesized via an ionothermal method in organic solvents. In contrast to well-established approaches, ZnCl2 is utilized as the pyrolysis-promoting agent to prepare emissive CDs with tunable wavelengths, directly by carbonization from different O and N precursors under a mild reaction condition at 210°C. More than 50% synthetic yield and 39% photoluminescent quantum yield (blue CD) are obtained. XAFS measurements, in conjunction with TEM, HAADF-STEM, UPS, and ESR analyses, allow us to obtain energy diagram configuration and confirm the luminescent nature of these hard-core structured CDs. Importantly, the resulting CDs exhibit excellent capability to photogenerate superoxide radical anion (O2⋅–), which can be exemplified by both photodynamic therapy and photooxidative cyclization synthesis of tetrahydroquinolines. Representative pharmaceutical mifepristone can be derivatized in 90% yield within 10 min of irradiation of the CDs in an elegant flow reactor. Highly crystalline and emissive carbon dots (CDs) are firstly synthesized via an ionothermal method in organic solvents. In contrast to well-established approaches, ZnCl2 is utilized as the pyrolysis-promoting agent to prepare emissive CDs with tunable wavelengths, directly by carbonization from different O and N precursors under a mild reaction condition at 210°C. More than 50% synthetic yield and 39% photoluminescent quantum yield (blue CD) are obtained. XAFS measurements, in conjunction with TEM, HAADF-STEM, UPS, and ESR analyses, allow us to obtain energy diagram configuration and confirm the luminescent nature of these hard-core structured CDs. Importantly, the resulting CDs exhibit excellent capability to photogenerate superoxide radical anion (O2⋅–), which can be exemplified by both photodynamic therapy and photooxidative cyclization synthesis of tetrahydroquinolines. Representative pharmaceutical mifepristone can be derivatized in 90% yield within 10 min of irradiation of the CDs in an elegant flow reactor. Synthesis of carbon dots (CDs), especially emissive CDs, has recently received great attention for their tremendous potential in a broad scope of applications.1Baker S.N. Baker G.A. Luminescent carbon nanodots: emergent nanolights.Angew. Chem. Int. Ed. 2010; 49: 6726-6744Crossref PubMed Scopus (3673) Google Scholar, 2Li L.-S. Yan X. Colloidal graphene quantum dots.J. Phys. Chem. 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However, these bottom-up methods are still encountering the detrimental effects from harsh conditions during synthesis (high pressure or temperature), solvent compatibility of precursors, tedious treatment procedure (chromatography, dialysis), relatively low yield, and discrete particle-size distribution. Toward an ideal approach, CDs are expected to be synthesized by conventional reactions in compatible solvents with selectable precursors as well as convenient post-reaction treatment and scalable preparation. Zinc chloride (ZnCl2), an inorganic salt with extremely low melting point of 283°C, has been used as dehydrating, condensating, or catalytic agents in chemical production, metallurgical fluxes, and material preparation. Fellinger and coworkers29Chang Y.Q. Antonietti M. Fellinger T.P. Synthesis of nanostructured carbon through ionothermal carbonization of common organic solvents and solutions.Angew. Chem. Int. 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Here, we utilize the excellent solubility of ZnCl2 in oxo solvents and develop a simple “wet chemistry” ionothermal method32Kuhn P. Antonietti M. Thomas A. Porous, covalent triazine-based frameworks prepared by ionothermal synthesis.Angew. Chem. Int. Ed. 2008; 47: 3450-3453Crossref PubMed Scopus (1709) Google Scholar to synthesize CDs, particularly highly crystalline and luminescent CDs with tunable emission wavelengths and potential for scalable production (Figure 1). In contrast to the current bottom-up pathways such as solvothermal synthesis or microwave pyrolysis,33Zhu S. Song Y. Shao J. Zhao X. Yang B. Non-conjugated polymer dots with crosslink-enhanced emission in the absence of fluorophore units.Angew. Chem. Int. Ed. 2015; 54: 14626-14637Crossref PubMed Scopus (280) Google Scholar,34Zhu S. Song Y. Zhao X. Shao J. Zhang J. Yang B. The photoluminescence mechanism in carbon dots (graphene quantum dots, carbon nanodots, and polymer dots): current state and future perspective.Nano Res. 2015; 8: 355-381Crossref Scopus (1644) Google Scholar solvent compatibility from organic reactants has been greatly broadened, and no specific apparatus (autoclaves) for high-pressure endurance is needed. Attributed to the excellent pyrolysis-promoting capability from ZnCl2 through ionothermal synthesis, a series of colorful CDs with hard-core structures and soft shells can be obtained by selectable precursors in controllable conditions. From a synthetic point of view, it is always a dilemma, to achieve CDs possessing both high luminescence and well-structured crystalline lattice.33Zhu S. Song Y. Shao J. Zhao X. Yang B. Non-conjugated polymer dots with crosslink-enhanced emission in the absence of fluorophore units.Angew. Chem. Int. Ed. 2015; 54: 14626-14637Crossref PubMed Scopus (280) Google Scholar,34Zhu S. Song Y. Zhao X. Shao J. Zhang J. Yang B. The photoluminescence mechanism in carbon dots (graphene quantum dots, carbon nanodots, and polymer dots): current state and future perspective.Nano Res. 2015; 8: 355-381Crossref Scopus (1644) Google Scholar The current approach to produce highly crystalline and emissive CDs is unprecedented. More strikingly, the CDs bearing rigid hard-core structure are able to generate superoxide radical anion (O2⋅–) both in aqueous media and organic solvents, which shows exceptional activity in photodynamic therapy and photooxidative cyclization reaction. Figure 2 shows the ZnCl2 pyrolysis for CD synthesis from various organic precursors. In the presence of ZnCl2, a diverse array of O and N precursors were experimentally tested in pairs (Table S1), to produce emissive CDs via this ionothermal synthesis. As high-boiling-point oxo solvents (tetraethylene glycol, ethylene glycol, and glycerol) were employed as the reaction media for solute compatibility, ZnCl2, a strong Lewis acid, was proved highly reactive and could even convert liquid solvent to solid foam carbon (Figures 2B and 2C). Limited by either poor solubility in organic solvents or poor stability under pyrolytic conditions, other metal chlorides (such as MnCl2, CoCl2, CaCl2, MgCl2, NiCl2, FeCl3, and AlCl3) showed pyrolytic-promoting ability inferior to ZnCl2. The gradual carbonization profiles of 8-hydroxyquinoline and p-phenylenediamine are presented as examples. Strikingly orange luminescence had been detected directly in the black and viscous solution (Figure 2). Control experiments from single precursors demonstrated well the importance of the combination formula strategy. Sole pyrolysis of 8-hydroxyquinoline offered bluish-green luminescence at 160°C, and further carbonization resulted in a distinct blue-shift to greenish blue as well as diminished luminescence (Figure 2D). In the case of sole m-phenylenediamine (Figure 2E) with incremental applied temperature, the reaction mixture presented an obvious red-shift in emissive color from blue, then to green and yellow, and finally to brown. Generally, the sole O precursor would be carbonized more substantially, resulting in weak photoluminescence in the blue region, while sole N precursors would generate colorful luminescent CDs but with slightly poor carbonization. The bluish CD normally bears higher N and lower O contents, and the reddish CD bears lower N and higher O contents (Table S2). Clearly, both the ZnCl2 agent and the temperature guaranteed the mild dehydrogenation and carbonization of all feeding organic precursors. During the ionothermal pyrolysis of “wet chemistry,” thin-layer chromatography monitoring indicated the complete disappearance of O and N precursors at optimized temperature of around 210°C, with deeper carbonization at higher temperature (240°C–280°C) leading to lower luminescence efficiency (Table S3). By precipitating in diethyl ether, the CD products were readily obtained as powder solids with yields of about 50% (based on the mass of feeding precursors), and excess ZnCl2 could be removed easily by utilizing its excellent solubility in oxo solvents. Moreover, all of these pyrolytic reactions were also applicable for gram-scale synthesis of CD products. Here we selected formulas of four precursors of acrylic acid and m-phenylenediamine, acrylic acid and 2,6-diaminopyridine, cysteine and p-phenylenediamine, and 8-hydroxyquinoline and p-phenylenediamine as instances of blue, green, yellow, and orange CDs (named B-, G-, Y-, and O-CD), respectively. Transmission electron microscopy (TEM) was employed to reveal the carbonized structure. Figures 3A–3D (see also Figures S1 and S2) show that all sample CDs presented well-dispersed distribution on the grid matrix with average particle sizes of approximately 4–6 nm. Structural analysis exhibited highly ordered hexagonal lattice fringes with spacing of 0.25 and 0.21 nm, corresponding to the (020) and (100) diffraction facets of graphite, respectively. Selected area electron diffraction patterns can be indexed to an ordered lattice typical (100), (102), (110), and (201) of rigid carbon structure (Figure 3D2). And a soft shell was also observed with about 1 nm thickness. The chemical composition of CDs was well interpreted by 1H nuclear magnetic resonance (Figures S3–S6). The greatly flattened peaks of CDs in chemical shifts indicated substantial diminishment of amino, aromatic, and alkane hydrogen functional groups after ZnCl2-catalyzed pyrolysis. The Fourier transform infrared spectra suggested some functional groups (Figure S7) remaining after carbonization, such as O–H (∼3,435 cm−1), C–H (∼2,925 cm−1), COOH (∼1,720 cm−1), C=O (∼1,625 cm−1), C–N (∼1,380 cm−1), C–O (∼1,260 cm−1), and C–O–C (∼1,100 cm−1). Irrespective the significant difference in feeding precursors, the greatly consumed NH2 and COOH groups demonstrated an effective carbonization during ionothermal synthesis by utilizing the pyrolysis-promoting agent of ZnCl2. X-ray powder diffraction patterns for these CDs presented broad (002) diffraction peaks around 23°, corresponding to a d-spacing of 0.38 nm, in agreement with typical carbon materials (Figure S8).29Chang Y.Q. Antonietti M. Fellinger T.P. Synthesis of nanostructured carbon through ionothermal carbonization of common organic solvents and solutions.Angew. Chem. Int. Ed. 2015; 54: 5507-5512Crossref PubMed Scopus (55) Google Scholar The Raman spectra presented a D band at 1,360 cm−1 and a G band at 1,585 cm−1 with broad width around 150 cm−1 (Table S4), corresponding to the vibrations of the termination plane of disordered graphite and sp2-hybridized carbon atoms in a two-dimensional hexagonal lattice, respectively (Figure S9).35Kurita S. Yoshimura A. Kawamoto H. Uchida T. Kojima K. Tachibana M. Molina-Morales P. Nakai H. Raman spectra of carbon nanowalls grown by plasma-enhanced chemical vapor deposition.J. Appl. Phys. 2005; 97: 104320Crossref Scopus (208) Google Scholar,36Tachibana M. Structural characterization of carbon nanowalls and their potential applications in energy devices.in: Wu Y. Shen Z. Yu T. Two-Dimensional Carbon Fundamental Properties, Synthesis, Characterization, and Applications. CRC Press, 2014: 121-152Google Scholar The peak intensity ratio ID/IG was found to vary in the range from 0.76 to 1.10, and the appearance of 2D (2,830 cm−1), D + G (3,020 cm−1), and 2D′ (3,240 cm−1) bands indicated the presence of less disorder and highly crystalline structure in these ionothermally synthesized CDs. High-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) images provided a clear zoom-in profile for CD samples. No Zn clusters were found embedded in the hard-core structure, and residual zinc ions (yellow circles) were distributed randomly on the soft shell of each CD (Figure 3E1). Electron energy loss spectroscopy (EELS) elemental maps from K edges (Figures 3E2–3E7) definitely indicated the coexistence of C, N, O, Cl, and Zn elements. The CD hard core is dominated by carbon, and the soft shell is composed of O and N functional groups (such as hydroxy, carboxy, and amino) as well as partially binding with Zn2+ ions. To further investigate the CD structure, we carried out X-ray photoelectron spectroscopy (XPS) measurements. The survey spectra indicated that all sample CDs consist of carbon (C 1s, 285 eV), oxygen (O 1s, 532 eV), and nitrogen (N 1s, 400 eV) elements (Figure S10); content analysis was qualitative, in agreement with that from elemental analysis (Table S2). The deconvolution of the high-resolution C 1s XPS spectra (Figure S11 and Table S5) revealed five conventional peaks at 284.5, 285.9, 286.2, 287.1, and 288.7 eV, corresponding to C=C/C–C in aromatic rings, C–N, C–OH (hydroxy), C=O (carbonyl), and COOH groups, respectively.25Pan L. Sun S. Zhang L. Jiang K. Lin H. Near-infrared emissive carbon dots for two-photon fluorescence bioimaging.Nanoscale. 2016; 8: 17350-17356Crossref PubMed Google Scholar In the meantime, the O 1s band was deconvoluted with only two peaks at 531.6 and 533.0 eV for C=O and C–O. Considering the configured hard-core and soft-shell structure, abundant O–H and COOH groups were distributed on the CD surface. The N 1s band represented three types of nitrogen species involving pyridinic N (398.4 eV), pyrrolic N (399.1 eV), and graphitic N (400.2 eV), indicating the N-doping both on the soft shell and in the hard core of CDs. Zn 2p XPS spectra gave the residual Zn contents from 6.27 wt % to 9.31 wt %, higher than the values determined by inductively coupled plasma mass spectrometry (ICP-MS), with actual zinc element contents of 5.91 wt % and 5.69 wt % for B-CD and O-CD, respectively. This result was consistent with the HAADF-STEM observation that the residual Zn ions prefer a surface tethering not in the hard core of CDs. With the aid of X-ray absorption fine structure (XAFS) measurements, Zn K-edge X-ray absorption near-edge structure spectra (Figure S12A) revealed a constant Zn2+ valence for CD samples. Corresponding |χ(R)| Fourier transform spectra (Figure S12B) and first shell fit to extended XAFS (Figure S13) confirmed the coexistence of Zn-N (2.10 Å), Zn-O (2.04 Å), and Zn-Cl (2.29 Å) coordination, which are different from organic ZnPPh complex (CAS no. 14074-80-7; pink line, Figure S12B), ZnCl2 (orange line), and ZnO (green line) as well.37Wu W. Zhang Q. Wang R. Zhao Y. Li Z. Ning H. Zhao Q. Wiederrecht G.P. Qiu J. Wu M. Synergies between unsaturated Zn/Cu doping sites in carbon dots provide new pathways for photocatalytic oxidation.ACS Catal. 2018; 8: 747-753Crossref Scopus (44) Google Scholar The synthesized CDs exhibited intense absorption with shoulder bands individually at 339, 441, and 536 nm for B-CD, G-CD, and O-CD, respectively (Figure 4A), and their extinction coefficient varied in the range from 15.4 to 23.7 L g−1 cm−1 at 339 nm with comparable turbidity (Table 1). As shown in Figure 4B, corresponding luminescence peaks were centered at 449 (B-CD), 520 (G-CD), 564 (Y-CD), and 590 nm (O-CD). The time-correlated single-photon counting decay profiles indicated biexponential lifetimes (τ1, τ2) of 1.64–13.00 ns for these CDs, and the corresponding luminescence quantum yield (Φ) was determined to be 39%, 23%, 7.4%, and 32%, respectively (Tables 1 and S6; Figure S14).Table 1Photophysical Parameters for CDsCDsaMeasured in deoxygenated water at 298 K.λabs (nm) (ε (L g−1 cm−1))λem (nm)τ1, τ2 (ns)τem (ns)ΦCB (V)VB (V)B-CD339 (15.4)4491.64, 5.112.560.39+1.82−0.94G-CD441 (8.93)5204.21, 10.047.900.23+1.61−0.77(18.3 @339)bFor absorption comparison at 339 nm.Y-CD–5642.52, 9.456.900.074+1.51−0.69(23.7 @339)bFor absorption comparison at 339 nm.O-CD536 (4.35)5903.49, 13.0010.040.32+1.45−0.65(21.3 @339)bFor absorption comparison at 339 nm.a Measured in deoxygenated water at 298 K.b For absorption comparison at 339 nm. Open table in a new tab The high Φ values were comparable with those prepared from solvothermal synthesis or microwave pyrolysis.38Lim S.Y. Shen W. Gao Z.Q. Carbon quantum dots and their applications.Chem. Soc. Rev. 2015; 44: 362-381Crossref PubMed Google Scholar One may suspect that the emission would originate from surficial complexation of Zn species. To address this issue, we determined the emission from model complex ZnPPh (pink line, Figure S15) or Zn-Salen (blue line, Figure S15; CAS no. 14167-22-7), and found a drastic difference in both absorption and emission spectra. Moreover, the emission of CDs shifted with varied excitation wavelengths (Figure S16), similar to the typical photophysical behavior of CDs reported in the literature.39Dong Y. Chen Y. You X. Lin W. Lu C.-H. Yang H.-H. Chi Y. High photoluminescent carbon based dots with tunable emission color from orange to green.Nanoscale. 2017; 9: 1028-1032Crossref PubMed Google Scholar,40Zhu S. Shao J. Song Y. Zhao X. Du J. 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Band structure engineering of carbon nitride: in search of a polymer photocatalyst with high photooxidation property.ACS Catal. 2013; 3: 912-919Crossref Scopus (374) Google Scholar According to the determined valence bands at +1.82, +1.61, +1.51, and +1.45 V and their maximal emission wavelengths at 449, 520, 564, and 590 nm for B-CD, G-CD, Y-CD, and O-CD, the conduction bands were determined as −0.94, −0.77, −0.69, and −0.65 V, respectively (Figure 4C, see details in Supplemental Information). Such a semiconductive characteristic was in good accordance with the performance in transient photocurrent responses (Figures S18 and S19). On the basis of the above results, we believe that, as a pyrolytic-promoting enabler, Zn2+ not only dehydrogenates/pyrolyzes the precursors in organic solvent with its strong Lewis acid nature, but also catalyzes the generation of highly crystalline carbon cores through a typical nucleation and growth mechanism (Figure 2A).31Bijani S. Schrebler R. Dalchiele E.A. Gabás M. Martínez L. Ramos-Barrado J.R. Study of the nucleation and growth mechanisms in the electrodeposition of micro- and nanostructured Cu2O thin films.J. Phys. Chem. C. 2011; 115: 21373-21382Crossref Scopus (50) Google Scholar The ionothermally synthesized CDs have a highly emissive hard core as well as a unique soft shell bearing abundant OH and COOH groups on the surface, both features ensuring their high solubility in aqueous and organic media and great potential in photochemical and biomedical applications. The luminescent CDs showed good biocompatibility in tumor cell lines of human hepatoma Bel-7402, human lung adenocarcinoma A549, and human cervical carcinoma HeLa, as well as normal epithelial cells of L929 (Figures 5A and S20). Interestingly, the CDs presented a significant difference in subcellular targeting capability toward organelles as imaged on a confocal microscope under a single 405-nm laser excitation. O-CD adheres to the cell membrane intensely, B-CD and Y-CD enter cytoplasm, while G-CD presents a strong affiliate to cell nucleus (Figures 5E and S21). Their variation in organelle-specific imaging might originate from the crystalline and emissive CD with unique hard core and soft shell. Most importantly, the synthesized CDs are able to generate superoxide radical anion (O2⋅–) effectively, thus exhibiting obvious photocytotoxicity (Figures 5B and S22). Electron spin resonance (ESR) spectroscopy confirmed the excellent photosensitizing capability of these CDs for O2⋅– generation under aerobic conditions (Figure 5C). As the valence state of Zn2+ ions remained before and after irradiation, the highly crystalline structure of semiconductor CDs was believed to be responsible for O2⋅– generation. Upon visible light irradiation, sufficient conduction-band energy of CDs drives the excited electron to molecular oxygen to produce O2⋅–. The corresponding intracellular O2⋅– level could be accessed by a dihydroethidium (DHE) staining assay. Upon irradiation, the red fluorescence from intercalated ethidium on RNA/DNA increased gradually and was accompanied by an obvious photogenerated cytotoxicity within 12 min (Figures 5F, 5G, and S23–S25). Severe cell shrinkage and blebs were observed, and the cytoplasmic content spilled into the extracellular milieu through the damaged plasma membrane due to high cellular oxidative stress induced by photogenerated O2⋅–. Quantitative analysis of intracellular O2⋅– levels with different CDs was conducted based on (2-(4-Iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium sodium salt (WST-1) superoxide detection assay. The absorbance of reduced WST-1 at 450 nm (Figure 5D) determined the rate for O2⋅– photogeneration as high as 2.94 μM min–1, with a relative quantum yield of 1.08% for B-CD (during the first 2 min), which is comparable with typical photosensitive hypericin (0.75%) used in photodynamic therapy.42Hadjur C. Jardon P. Quantitative analysis of superoxide anion radicals photosensitized by hypericin in a model membrane using the cytochrome c reduction method.Photochem. Photobiol. B: Biol. 1995; 29: 147-156Crossref Scopus (29) Google Scholar To further reveal the efficacy of photodynamic therapy (PDT) for CDs in vivo, we intravenously administered tumor-bearing mice with O-CD for treatment (Figure 6A). After PDT with a laser (589 nm, 0.5 W cm−2), the tumors were successfully ablated and had not recurred within 16 days' observation. Monitoring on tumor volumes of control groups showed more than 15-fold growth over the same period (Figure 6C). Meanwhile, the body weights in all mouse groups (Figure 6D) presented sustained growth and the survival rates remained at 100% (n = 5). Histological examination from hematoxylin and eosin (H&E) staining showed that the tumor tissues treated with both CD and laser irradiation exhibited extensive karyopyknosis and necrosis, and no appreciable physiological morphology changes and adverse effects were observed in major organs (Figures 6B and S26). In addition, in vivo fluorescent imaging indicated maximal fluorescence on tumor tissue appearing at 4 h post injection (Figure 6E). Corresponding ex vivo fluorescence imaging indicated that the CDs accumulated significantly in liver, kidney, and tumor tissue (Figure 6F). All of these results demonstrated an efficient and biocompatible PDT treatment in vivo. To make full use of the high reactivity for O2⋅– photogeneration, we applied these CDs to organic photosynthesis of tetrahydroquinoline via a photosensitized cyclization in solution.43Yang X.-L. Guo J.-D. Lei T. Chen B. Tung C.-H. Wu L.-Z. Oxidative cyclization synthesis of tetrahydroquinolines and reductive hydrogenation of maleimides under redox-neutral conditions.Org. Lett. 2018; 20: 2916-2920Crossref PubMed Scopus (48) Google Scholar,44Nicholls T.P. Constable G.E. Robertson J.C. Gardiner M.G. Bissember A.C. Brønsted acid cocatalysis in copper(I)-photocatalyzed α-amino C-H bond functionalization.ACS Catal. 2016; 6: 451-457Crossref Scopus (76) Google Scholar Superior to a model photosensitizer, either ZnPPh or Zn-Salen, all four CD samples exhibit distinct photocatalytic activities (Table S7). In the case of B-CD and G-CD, there is more than 60% reactive enhancement compared with even the best performance of photocatalytic carbonitrile g-C3N4,45Lin L. Yu Z. Wang X. Crystalline carbon nitride semiconductors for photocatalytic water splitting.Angew. Chem. Int. Ed. 2019; 58: 6164-6175Crossref PubMed Scopus (335) Google Scholar the reactivities upon irradiation are in good agreement with the O2⋅–-generating rates determined by ESR or WST-1 assay. The excellent yield, >98%, based on the consumption of starting material, for the reaction between maleimide and aniline was achieved within 10 min of irradiation of CDs in an elegant flow reactor (Figures S27–S29) under air atmosphere, with good reproducibility (Figure 1 and Table S8). In addition, this oxidative cyclization could be easily expanded to the derivatization of pharmaceutical mifepristone in a yield of 90%, demonstrating that these highly crystalline and emissive CDs could be facilely applied as effective, low cost, and environmentally friendly photosensitizers for chemical reactions. In summary, we report the first synthesis of highly crystalline and emissive CDs enabled by ZnCl2 as the pyrolysis-promoting agent in organic solvents. Through the formula combination from different N and O precursors, emissive CDs with tunable wavelengths can be synthesized directly by ionothermal pyrolysis at ambient atmosphere. More than 50% synthetic yield and 39% photoluminescent quantum yield are obtained. XAFS measurements, in conjunction with TEM, HAADF-STEM, UPS, and ESR analysis, allow us to obtain energy diagram configuration and confirm the luminescent nature of these hard-core structured CDs. Importantly, these CDs exhibit excellent capability to photogenerate superoxide radical anion O2⋅–, which can be exemplified by both photodynamic therapy and photooxidative cyclization synthesis of tetrahydroquinolines. A representative pharmaceutical, mifepristone, can be derivatized in 90% yield (based on the consumption of starting materials) within 10 min of irradiation of the CDs in an elegant flow reactor. This study not only offers a simple “wet chemistry” ionothermal strategy toward the synthesis of highly crystalline and emissive CDs but also paves a new way to apply these CDs in advanced photochemistry.