Zizibabin light-emitting double-free-radical material as well as preparation method and application thereof

Abstract

The invention relates to a Zizibabin light-emitting double-free-radical material, a preparation method and application of the Zizibabin light-emitting double-free-radical material in preparation of biological imaging preparations or anti-tumor drugs, and belongs to the technical field of tumor treatment. According to the Zizibabin light-emitting double free radical, two triphenylmethyl carbon free radicals are taken as free radical centers and are connected with four donor groups, so that the light stability and the light-induced quantum yield are obviously improved. The invention provides a high-efficiency and stable near-infrared luminous zizibabin double-free-radical compound, and the material has the characteristics of near-infrared emission and high photothermal conversion efficiency, has good heating capacity and thermal stability, and can be prepared into water-soluble nanoparticles to be applied to fluorescence imaging and photothermal therapy in organisms. According to the synthesis and expansion of the Zizibabin luminous double-free-radical compound, the types of luminous double free radicals are greatly enriched, and the application of the Zizibabin luminous double-free-radical compound in more fields is further possible.

Description

Technical Field

[0001] The present invention belongs to the technical field of tumor treatment, and specifically relates to a chichibabin-type luminescent biradical material, a preparation method and application thereof in the preparation of biological imaging preparations or anti-tumor drugs. Background Art

[0002] Organic diradical compounds have attracted extensive attention due to their unique bonding mode, interesting physical properties and potential applications in functional materials. Although their synthesis process is relatively complicated, the research value of this type of compounds is still significant. A typical example is the triphenylmethyl diradical, Chichibabin hydrocarbon, which was first synthesized by Tschitschibabin in 1907 and has been the subject of research by scientists for more than a century. Due to their strong spin coupling effect, these molecules usually exhibit narrow band gaps and significant light absorption, especially in the near-infrared region, which makes them ideal candidates for photothermal agents. However, these compounds have high chemical reactivity and usually show instability. In addition, like most organic diradicals, Chichibabin-type luminescent diradical compounds have a small energy gap and strong spin coupling, which leads to an increase in the Franck-Condon factor, thereby increasing internal conversion, making their photoluminescence quantum efficiency very low or even non-luminescent, which limits their application in the optical field. Therefore, the development of stable near-infrared luminescent Chichibabin-type diradical compounds is a major challenge in the field of photothermal tumor therapy. Summary of the invention

[0003] In order to solve the problems of the prior art, the primary purpose of the present invention is to provide a near-infrared luminescent Chichibabin-type luminescent diradical compound, which has excellent stability, unique luminescent properties and high photothermal conversion efficiency, and is a new type of functional material.

[0004] The second object of the present invention is to provide a method for preparing the above-mentioned near-infrared luminescent chichibabin-type luminescent diradical compound to achieve the successful synthesis of the new compound.

[0005] The third purpose of the present invention is to provide the application of the above-mentioned near-infrared luminescent chichibabin-type luminescent diradical compound in the preparation of biological imaging preparations or photothermal therapeutic anti-tumor drugs, so as to expand its potential use in the medical field.

[0006] The present invention discloses a near-infrared luminescent diradical compound of the type Tschibabin type, which is an open-shell luminescent diradical compound with a quinone structure, and is a trityl carbon radical as a diradical center and connected to four donor groups. The structure of the diradical compound of the type Tschibabin type is 2R 1 -RR-2R1 , RR in the structure is a trityl carbon diradical center, R 1 is the donor group.

[0007] Furthermore, the structural formula of the trityl carbon free radical is as follows:

[0008]

[0009] Formula I, Formula II and Formula III are trityl carbon free radical precursors, which are derived from tris(2,4,6-trichlorophenyl)methane, (2,4,6-trichloro-3-pyridyl)bis(2,4,6-trichlorophenyl)methane and bis(2,4,6-trichloro-3-pyridyl)(2,4,6 trichlorophenyl)methane, respectively.

[0010] The structural formula of the Qiqibabin-type luminescent diradical compound is as follows:

[0011]

[0012] Furthermore, the donor group R of the Chichibabin-type luminescent diradical compound is 1 It can be one of triphenylamine, benzylcarbazole, carbazole indole, benzofuran carbazole, benzothiophene carbazole, triisopropylphenyl carbazole, naphthyl acridine, pyrazine indole, indole quinoxaline, benzene, naphthalene, and anthracene groups. The specific structure is shown below, but it is not limited to the above groups.

[0013]

[0014] The four R in Formula II of the present invention are 1 When the radical is a chlorine atom (Cl), it is called a diradical TTM-TTM. 1 When the group is a benzocarbazole group as shown in Formula 2, it is called a diradical TT-CzPh.

[0015] The preparation method of the chichibabin-type luminescent diradical compound of the present invention comprises the following steps:

[0016] (1) Under a protective atmosphere, a trityl carbon free radical precursor tris(2,4,6-trichlorophenyl)methane, a donor group compound 9-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole, a ligand-acting 2-dicyclohexylphosphine-2',6'-dimethoxy-1,1'-biphenyl, and a catalyst tetrakis-(triphenylphosphine)palladium are mixed in a molar ratio of 18-24:48-52:1.0:1.0 in a liquid medium. A potassium phosphate aqueous solution (concentration 1-3M) and tetrahydrofuran with a volume ratio of 1.0:2-6 are mixed and reacted in the dark, the reaction temperature is 85-95°C, and the reaction time is 22-26 hours; after the reaction is completed, the mixture is cooled to room temperature and extracted with dichloromethane, the obtained organic extract is dried over anhydrous magnesium sulfate and the solvent is removed under reduced pressure, and the obtained crude product is further purified by silica gel column with an eluent (the volume ratio of dichloromethane to petroleum ether is 1.0:5-8) to obtain a donor disubstituted monoradical precursor;

[0017] (2) under a protective atmosphere, the donor disubstituted monoradical precursor obtained in step (1), the bis-pinacol borate, the ligand compound 2-dicyclohexylphosphine-2',6'-dimethoxy-1,1'-biphenyl, the catalyst tetrakis-(triphenylphosphine)palladium and potassium acetate are mixed in a volume of 30-40 mL of 1,4-dioxane in a molar ratio of 15-18:23-27:1-2:1.0:28-32, and the reaction is carried out in the dark at a temperature of 75-85° C. for a reaction time of 22-26 h. After the reaction is completed, the monoradical precursor is extracted with dichloromethane after cooling to room temperature. The obtained organic extract is dried over anhydrous magnesium sulfate and the solvent is removed under reduced pressure. The obtained crude product is further purified by silica gel column with an eluent (the volume ratio of ethyl acetate to petroleum ether is 1.0:7-10) to obtain a boronated donor disubstituted monoradical precursor;

[0018] (3) under a protective atmosphere, the donor disubstituted monoradical precursor obtained in step (1), the boronated donor disubstituted monoradical precursor obtained in step (2), the ligand compound 2-dicyclohexylphosphine-2',6'-dimethoxy-1,1'-biphenyl and the catalyst bis(dibenzylideneacetone)palladium are added to a potassium carbonate aqueous solution and 1,4-dioxane in a volume ratio of 1.0:2-6 in a molar ratio of 24-26:24-26:1-2:1.0, and mixed, wherein the concentration of the potassium carbonate solution is 2 mol·L -1 , the reaction was carried out in the dark, the reaction temperature was 75-85°C, the reaction time was 22-26h, after the reaction was completed, the reaction was cooled to room temperature and then extracted with dichloromethane, the obtained organic extract was dried over anhydrous magnesium sulfate and the solvent was removed under reduced pressure, the obtained crude product was further purified by silica gel column with eluent (the volume ratio of dichloromethane to petroleum ether was 1.0:2-5) to obtain the chichibabin-type diradical precursor;

[0019] (4) Under a protective atmosphere, the chichibabin-type diradical precursor obtained in step (3) is mixed with tetrahydrofuran, potassium tert-butoxide is added in a dark environment and stirred, and tetrachlorobenzoquinone is added and reacted for 4 to 8 hours after stirring at room temperature for 10 to 20 hours, wherein the molar ratio of the precursor, potassium tert-butoxide and tetrachlorobenzoquinone is 1.0:80 to 86:80 to 86, and the solvent is removed under reduced pressure. The crude product is further separated and purified by a silica gel column using an eluent (the volume ratio of dichloromethane to petroleum ether is 1.0:2 to 5) to obtain the chichibabin-type luminescent diradical compound.

[0020] The method for preparing the Tsitchibabin-type luminescent diradical compound of the present invention follows the following principles: First, the original Tsitchibabin hydrocarbon framework is selected to ensure its near-infrared luminescent properties, and its luminescent stability is enhanced by selectively chlorinating the hydrogen atoms. Second, in order to further optimize the photophysical properties, a mild donor group is introduced to replace the four peripheral chlorine atoms of TTM-TTM, thereby adjusting the degree of donor conjugation. Therefore, in the process of preparing the Qiqibabin-type luminescent diradical compound, the present invention first selects a trityl carbon radical precursor and a boronized donor group as starting materials, and performs a mixed reaction in a protective gas environment to obtain a donor disubstituted monoradical precursor; secondly, the donor disubstituted monoradical precursor is reacted with substances such as a bis-pinacol borate to generate a boronized donor disubstituted monoradical precursor; then, the donor disubstituted monoradical precursor is reacted with a boronized donor disubstituted monoradical precursor to obtain the target Qiqibabin-type diradical precursor; finally, an oxidation reaction is performed to obtain a Qiqibabin-type luminescent diradical compound with near-infrared luminescent characteristics. The entire synthesis process is carried out in a protective gas atmosphere, and the light-avoiding operation is strictly followed to ensure that the four chlorine atoms can be completely replaced, thereby ensuring the luminescent performance and stability of the final product.

[0021] The application of the chichibabin-type luminescent biradicals, the prepared photothermal anti-tumor nanomedicine with near-infrared luminescence and at least one of biological imaging.

[0022] Compared with the prior art, the technical solution of the present invention has the following beneficial effects:

[0023] The introduction of peripheral donor molecules into the chichibabin-type luminescent diradicals proposed by the present invention significantly improves the photostability and photoinduced quantum yield of the free radicals, and furthermore, has excellent luminescence characteristics in the near-infrared region.

[0024] The chichibabin-type luminescent biradical material described in the present invention has high photothermal conversion efficiency and has great application potential in photothermal therapy.

[0025] The synthesis and expansion of the Chichibabin-type luminescent diradicals described in the present invention greatly enrich the types of luminescent diradicals, and further make their application in more fields possible. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 : Matrix-assisted laser desorption / ionization time-of-flight mass spectrometry of the TT-CzPh compound prepared in Example 1;

[0027] Figure 2 : Electron paramagnetic resonance spectrum of the TT-CzPh powder sample prepared in Example 1 at 295K, the inset shows Δm s = ±2 resonance, confirming its diradical nature;

[0028] Figure 3 : The variable temperature electron paramagnetic resonance spectrum of the TT-CzPh powder sample prepared in Example 1 in the range of 220 to 370 K confirms the existence of the open shell singlet ground state;

[0029] Figure 4 : The UV absorption spectrum and photoluminescence spectrum of TT-CzPh prepared in Example 1 in toluene have a maximum absorption wavelength of 785 nm and an emission spectrum of 822 nm;

[0030] Figure 5 : Transmission electron microscopy image of TT-CzPh nanoparticles prepared in Example 3, the nanoparticles present a uniform spherical structure;

[0031] Figure 6 : The ultraviolet absorption spectrum and photoluminescence spectrum of the TT-CzPh nanoparticles prepared in Example 3 show that the emission peak of the TT-CzPh nanoparticles is located at 822 nm, which is consistent with the emission peak position of the diradical TT-CzPh;

[0032] Figure 7 : The TT-CzPh nanoparticles of different concentrations prepared in Example 3 were tested at a wavelength of 655 nm and a power density of 1.0 W·cm -2 The temperature rise curve under laser irradiation shows that compared with water, the higher the concentration of nanoparticles, the higher the temperature of the solution after irradiation, indicating that the temperature change of the aqueous solution of nanoparticles is positively correlated with the concentration of nanoparticles.

[0033] Figure 8 : The concentration obtained in Example 3 is 50 μg·mL -1 The temperature rise curve of TT-CzPh nanoparticles under laser irradiation of different power densities at a wavelength of 655nm. Compared with water, the greater the laser power, the higher the solution temperature after irradiation, indicating that the temperature change of the aqueous solution of nanoparticles is positively correlated with the laser power.

[0034] Fig. 9 : The concentration obtained in Example 3 is 50 μg·mL -1 The power density of TT-CzPh nanoparticles at a wavelength of 655 nm was 1.0 W cm -2 The five-cycle temperature rise / fall curve under laser irradiation shows that the temperature rise effect of the nanoparticles after five cycles of irradiation has no significant change compared with that before irradiation, indicating that the nanoparticles have good photothermal stability.

[0035] Fig.10 : The photothermal conversion efficiency curve of the TT-CzPh nanoparticle aqueous solution prepared in Example 3, the photothermal conversion efficiency of the nanoparticles was calculated to be 82.23%;

[0036] Fig.11 : Fluorescence imaging of the TT-CzPh nanoparticles prepared in Example 3 in mice. One hour after the injection of the nanoparticles, obvious fluorescence signals began to appear at the tumor site of the mouse. As time went on, at 9 hours, the fluorescence signal at the tumor reached the strongest, indicating that the best time for treatment was 9 hours after the injection of the nanoparticles. As time went on, the fluorescence information of the nanoparticles at the tumor gradually weakened until it completely disappeared at 48 hours, indicating that the administration time of the mice was controlled at about 48 hours.

[0037] Fig.12 : The average relative tumor volume changes of untreated mice and treated mice within 14 days (a) and the in vitro tumor volume picture after 14 days (b), where PBS-L represents the group without laser irradiation after injection of buffer solution, PBS+L represents the group with laser irradiation after injection of buffer solution, TT-CzPh NPs-L represents the group without laser irradiation after injection of TT-CzPh nanoparticles, and TT-CzPh NPs+L represents the group with laser irradiation after injection of TT-CzPh nanoparticles; Fig.12 It shows that TT-CzPh nanoparticles have a good killing effect on tumors in mice under laser irradiation. The tumor volume of mice is significantly reduced, and some mice can even be cured. DETAILED DESCRIPTION

[0038] The experimental methods described in the following examples are conventional methods unless otherwise specified, the room temperature is 25±2° C., and the reagents and materials are commercially available unless otherwise specified. The technical solutions of the present invention are further illustrated by examples.

[0039] Example 1: Qiqibabin luminescent diradical TT-CzPh (diradical core is formula II, R 1 The synthesis of formula 2)

[0040]

[0041] (1) Under argon protection, tri(2,4,6-trichlorophenyl)methane (4.0 g, 7.2 mmol), 9-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole (6.6 g, 18 mmol), ligand 2-dicyclohexylphosphine-2',6'-dimethoxy-1,1'-biphenyl (0.148 g, 0.36 mmol) and catalyst tetrakis-(triphenylphosphine)palladium (0.416 g, 0.36 mmol) were mixed in a two-necked flask filled with tetrahydrofuran (200 mL) and potassium phosphate aqueous solution (50 mL, 2 M), and the mixture was heated to 90° C. in an argon atmosphere to react for 24 h. After the reaction mixture was cooled to room temperature, it was extracted with dichloromethane. The obtained organic extract was dried over anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The obtained crude product was further purified by silica gel column using an eluent (dichloromethane: petroleum = 1:6 (volume ratio)) to obtain 2.8 g of white powder of donor disubstituted monoradical precursor compound 1 with a yield of 40%.

[0042] 1 H NMR (500MHz, CD 2 Cl 2 )δ8.42(s,1H),8.21(d,J=7.8Hz,1H),7.80(s,1H),7.69(d,J=8.7Hz,1H),7.67–7.63(m,3H),7.61(d, J=7.5Hz,2H),7.51(dd,J=16.8,8.0Hz,2H),7.45(d,J=6.0Hz,2H),7.33(t,J=6.5Hz,2H),6.93(s,1H). 13 C NMR (500MHz, CD 2 Cl 2 )δ143.44,142.28,141.76,138.44,138.14,137.88,137.81,135.92,134.16,133.92,130.78,130.41,12 9.16,128.50,127.78,127.51,127.24,125.66,124.76,124.01,121.14,119.47,111.11,110.83,51.11.

[0043] MALDI-TOF(m / z):Calculated for C 55 H 31 Cl 7 N 2 :968.02,Found[M + ]:968.05.

[0044] (2) Under argon atmosphere, compound 1 (1.4 g, 1.5 mmol) obtained in step (1), bis-pinacol borate (0.573 g, 2.25 mmol), ligand 2-dicyclohexylphosphine-2',6'-dimethoxy-1,1'-biphenyl (0.0616 g, 0.15 mmol), catalyst tetrakis-(triphenylphosphine) palladium (0.0518 g, 0.09 mmol), potassium acetate (0.265 g, 2.7 mmol) were mixed in a two-necked flask filled with 1,4-dioxane (35.0 mL), and the mixture was heated to 80° C. and refluxed for 24 h under argon light-proof atmosphere. After the reaction mixture was cooled to room temperature, it was extracted with dichloromethane, and the obtained organic extract was dried over anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The obtained crude product was further purified by silica gel column with an eluent (ethyl acetate: petroleum ether=1:8 (volume ratio)) to obtain 0.54 g of boronated donor disubstituted monoradical precursor compound 2 as a white powder with a yield of 34%.

[0045] 1 H NMR (500MHz, CD 2 Cl 2 )δ8.46(s,2H),8.25(d,J=7.7Hz,2H),7.83(dd,J=8.8,1.6Hz,2H),7.80(s,1H),7.73(d,J=8.7Hz,2H),7.71–7.67(m,7H),7 .65(d,J=7.5Hz,4H),7.55(dd,J=16.6,8.0Hz,4H),7.49(d,J=6.0Hz,4H),7.37(t,J=6.6Hz,2H),7.02(s,1H),1.39(s,12H). 13 C NMR (500MHz, CD 2 Cl 2 )δ142.48,141.47,140.94,138.75,137.87,137.36,137.14,137.04,136.57,135.97,134.09,133.56,129.97,129.70,128.32, 127.68,126.99,126.62,126.42,124.87,123.94,123.23,120.31,118.67,110.29,110.01,109.89,84.50,50.87,24.68,24.62.

[0046] MALDI-TOF(m / z):Calculated for C 61 H 43 BCl6 N 2 O 2 :1059.54,Found[M + ]:1059.54.

[0047] (3) Under argon atmosphere, compound 1 (0.484 g, 0.5 mmol) obtained in step (1), compound 2 (0.530 g, 0.5 mmol) obtained in step (2), ligand 2-dicyclohexylphosphine-2',6'-dimethoxy-1,1'-biphenyl (0.0123 g, 0.03 mmol), and catalyst bis(dibenzylideneacetone)palladium (0.0115 g, 0.02 mmol) were mixed in a two-necked flask containing 1,4-dioxane (20.0 mL) and potassium carbonate aqueous solution (5.0 mL, 2 M), and the mixture was heated to 80° C. and refluxed for 24 h. After the reaction mixture was cooled to room temperature, it was extracted with dichloromethane, and the obtained organic extract was dried over anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The crude product was further purified by silica gel column using an eluent (dichloromethane: petroleum ether = 1:2.5 (volume ratio)) to obtain 0.49 g of white powder of the chichibabin-type diradical precursor HTHT-CzPh with a yield of 53%.

[0048] 1 H NMR (500MHz, CD 2 Cl 2 )δ8.43(s,4H),8.21(d,J=7.8Hz,4H),7.82(s,4H),7.72(d,J=5.3Hz,4H),7.68(t,J=5.4Hz,7H),7.65(d,J=7.5H z,7H),7.63–7.58(m,10H),7.51(dd,J=14.2,7.9Hz,8H),7.47–7.42(m,8H),7.33(t,J=6.7Hz,4H),7.02(s,2H). 13 C NMR (500MHz, CD 2 Cl 2 )δ143.17,142.07,141.54,138.95,138.46,138.35,138.07,137.94,137.72,136.71,134.00,130.56,130.2 5,128.96,128.28,127.57,127.27,127.02,125.47,124.55,123.82,120.92,119.27,110.89,110.60,51.16.

[0049] MALDI-TOF(m / z):Calculated for C 110 H 62 Cl 12 N 4 :1865.13,Found[M + ]:1865.61.

[0050] (4) Under argon atmosphere, HTHT-CzPh (0.3 g, 0.16 mmol) obtained in step (3) was added to an ultra-dry tetrahydrofuran solution in a two-necked flask, and potassium tert-butoxide (1.5 g, 13.3 mmol) was added while continuously passing argon and keeping away from light. After stirring at room temperature for 15 h, 2,3,5,6-tetrachlorobenzoquinone (3.3 g, 13.3 mmol) was added, and the reaction was continued with stirring for 6 h. After the reaction was completed, the solvent was removed under reduced pressure. The obtained crude product was further separated and purified by silica gel column with eluent (dichloromethane: petroleum ether = 1:3 (volume ratio)), and finally 0.08 g of dark blue-green solid TT-CzPh luminescent diradical was obtained, with a yield of 27%.

[0051] MALDI-TOF(m / z):Calculated for C 110 H 60 Cl 12 N 4 :1863.12,Found[M + ]:1863.36.Elem.Anal.Calcd for C 110 H 60 Cl 12 N 4 :C 70.91,H 3.25,N 3.01.Found,C71.04,H6.42,N 1.75.

[0052] Example 2: Property verification based on TT-CzPh

[0053] In this example, the structure of TT-CzPh was confirmed by matrix-assisted laser desorption / ionization time-of-flight mass spectrometry, elemental analysis, electron paramagnetic resonance spectroscopy, UV-visible absorption spectroscopy, and the like, and its related properties were studied.

[0054] Figure 1 This is the matrix-assisted laser desorption / ionization time-of-flight mass spectrometry of TT-CzPh. It can be seen that the tested molecular weight corresponds to the theoretically calculated molecular weight, confirming the molecular formula and structure of TT-CzPh.

[0055] Figure 2 This is the electron paramagnetic resonance spectrum of TT-CzPh powder at 295K. It can be seen that in Δms = ±1 region shows singlet electron paramagnetic resonance signal, which is observed at 295K with Δm s The additional signals corresponding to the =±2 transitions confirm its diradical nature. Figure 3 This is the electron paramagnetic resonance spectrum of TT-CzPh powder at 220~370K. The signal intensity gradually decreases with decreasing temperature, confirming the existence of the open shell singlet ground state.

[0056] Figure 4 The UV-visible absorption spectrum and photoluminescence spectrum of TT-CzPh in toluene solution. The results of spectral test show that the maximum absorption wavelength of TT-CzPh is 785nm, the emission spectrum is 822nm, and its photoluminescence quantum yield is 5.20% by calculation. In addition, in polymethyl methacrylate film, the photoluminescence quantum yield of TT-CzPh reaches 6.40%. This shows that by breaking the alternating symmetry and adjusting the donor conjugation, the expansion of the external structure of the molecule plays an important role in its radiation decay process.

[0057] Example 3: Preparation and property verification of TT-CzPh nanoparticles

[0058] (1) Preparation of TT-CzPh nanoparticles

[0059] TT-CzPh nanoparticles were prepared by self-assembly nanoprecipitation method using amphiphilic polymer distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-mPEG2000) as encapsulation agent. First, uniformly dispersed TT-CzPh (0.5 mg mL -1 ) and DSPE-mPEG2000 (5.0 mg mL -1 ) 1mL of tetrahydrofuran mixed solution. Under vigorous stirring, the above 1mL mixed solution was added dropwise to 9mL of ultrapure water, stirred at room temperature for 48h, and the filtrate was collected by filtration using a 0.22μm microporous membrane. Then, the solution was dialyzed for 48h using a dialysis bag with a molecular weight cutoff of 3.5kDa to remove the residual organic solvent tetrahydrofuran. After the dialysis, the solution was centrifuged using an ultrafiltration tube with a molecular weight cutoff of 3kDa to remove excess solvent water and concentrated to 1mg·mL -1 Finally, the concentrated TT-CzPh nanoparticle solution was stored in a 4°C refrigerator away from light for future use.

[0060] (2) Study on the properties of TT-CzPh nanoparticles

[0061] Figure 5 This is a transmission electron microscope image of the TT-CzPh nanoparticles prepared in Example 3. It can be seen that the nanoparticles are spherical in structure and have an average size of about 108.9 nm. Figure 6 Figure 3 is the UV-visible absorption spectrum and photoluminescence spectrum of TT-CzPh nanoparticles in aqueous solution. It can be clearly seen that the emission peak of the nanoparticles is located at 822nm.

[0062] Figure 7 The power density of TT-CzPh nanoparticles with different concentrations at a wavelength of 655 nm is 1 W·cm -2 The heating curve under laser irradiation is Figure 8 The concentration is 50 μg mL -1 The temperature rise curves of TT-CzPh nanoparticles under laser irradiation with a wavelength of 655nm and different power densities show that the temperature change in the aqueous solution of TT-CzPh nanoparticles is positively correlated with the concentration and laser power density.

[0063] Fig. 9 The concentration is 50 μg mL -1 The power density of TT-CzPh nanoparticles at a wavelength of 655 nm was 1 W cm -2 The five temperature rise / fall curves under laser irradiation show that the nanoparticles have good photothermal stability and the photothermal capacity is repeatable. The photothermal conversion efficiency of TT-CzPh nanoparticles is 82.23% ( Fig.10 ).

[0064] The above data prove that TT-CzPh nanoparticles are an ideal photothermal material for tumor treatment and can be used to prepare anti-tumor drugs.

[0065] Example 4: Biological applications based on TT-CzPh nanoparticles

[0066] (1) In vivo fluorescence imaging based on TT-CzPh nanoparticles

[0067] Fig.11 This is a fluorescence imaging picture of TT-CzPh nanoparticles in Balb / c tumor-bearing mice. The fluorescence signal reached its peak at 9 hours after injection of the nanoparticles and almost disappeared at 48 hours, indicating that the nanoparticles have the effect of in vivo imaging in mice and can be metabolized within 48 hours, thus determining the optimal treatment window and administration time.

[0068] (2) In vivo tumor treatment based on TT-CzPh nanoparticles

[0069] Fig.12 The average relative tumor volume change curve of untreated and treated mice within 14 days (a) and the in vitro tumor volume picture after 14 days (b) show that laser irradiation 9 hours after nanoparticle injection can significantly inhibit tumor growth in mice and achieve the purpose of photothermal killing of tumor cells.

[0070] In summary, the present invention discloses the preparation and biological application of a Chichibabin-type diradical material with stable near-infrared luminescence and high photothermal conversion efficiency.

Claims

1. A luminescent diradical compound of the type Qiqibabin, whose structural formula is shown in one of the following: R1 is one of triphenylamine, benzylcarbazole, carbazole indole, benzofuran carbazole, benzothiophene carbazole, triisopropylphenyl carbazole, naphthyl acridine, pyrazine indole, indole quinoxaline, benzene, naphthalene, and anthracene groups.

2. The chichibabin-type luminescent diradical compound according to claim 1, characterized in that: R1 is one of the following groups.

3. A method for preparing a chichibabin-type luminescent diradical compound according to claim 1 or 2, comprising the following steps: (1) Under a protective atmosphere, a trityl carbon free radical precursor, a donor group compound 9-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole, 2-dicyclohexylphosphine-2',6'-dimethoxy-1,1'-biphenyl as a ligand, and a catalyst tetrakis-(triphenylphosphine)palladium are mixed in a volume ratio of 1.0:2-6 at a molar ratio of 18-24:48-52:1.0:1.

0. A potassium phosphate aqueous solution (concentration 1-3M) and tetrahydrofuran are mixed and reacted in the dark, the reaction temperature is 85-95°C, and the reaction time is 22-26 hours; after the reaction is completed, the mixture is cooled to room temperature and extracted with dichloromethane, the obtained organic extract is dried over anhydrous magnesium sulfate and the solvent is removed under reduced pressure, and the obtained crude product is further purified by silica gel column with an eluent to obtain a donor disubstituted monoradical precursor; the eluent is a mixture of dichloromethane and petroleum ether, and the volume ratio thereof is 1.0:5-8; (2) under a protective atmosphere, the donor disubstituted monoradical precursor obtained in step (1), bis-pinacol borate, ligand compound 2-dicyclohexylphosphine-2',6'-dimethoxy-1,1'-biphenyl, catalyst tetrakis-(triphenylphosphine)palladium and potassium acetate are mixed in a volume of 30-40 mL of 1,4-dioxane in a molar ratio of 15-18:23-27:1-2:1.0:28-32, and reacted in the dark at a temperature of 75-85°C for a reaction time of 22-26 hours. After the reaction is completed, the mixture is cooled to room temperature and extracted with dichloromethane. The obtained organic extract is dried over anhydrous magnesium sulfate and the solvent is removed under reduced pressure. The obtained crude product is further purified by silica gel column with an eluent to obtain a boronated donor disubstituted monoradical precursor; the eluent is a mixture of ethyl acetate and petroleum ether in a volume ratio of 1.0:7-10; (3) under a protective atmosphere, the donor disubstituted monoradical precursor obtained in step (1), the boronated donor disubstituted monoradical precursor obtained in step (2), the ligand compound 2-dicyclohexylphosphine-2',6'-dimethoxy-1,1'-biphenyl and the catalyst bis(dibenzylideneacetone)palladium are added to a potassium carbonate aqueous solution and 1,4-dioxane in a volume ratio of 1.0:2-6 in a molar ratio of 24-26:24-26:1-2:1.0, and mixed, wherein the concentration of the potassium carbonate solution is 2 mol·L -1 , the reaction is carried out in the dark, the reaction temperature is 75-85°C, the reaction time is 22-26h, after the reaction is completed, the reaction is cooled to room temperature and then extracted with dichloromethane, the obtained organic extract is dried over anhydrous magnesium sulfate and the solvent is removed under reduced pressure, the obtained crude product is further purified by silica gel column with eluent to obtain the chichibabin-type diradical precursor; the eluent is a mixture of dichloromethane and petroleum ether, and the volume ratio thereof is 1.0:2-5; (4) Under a protective atmosphere, the chichibabin-type diradical precursor obtained in step (3) is mixed with tetrahydrofuran, potassium tert-butoxide is added in a dark environment and stirred, and tetrachlorobenzoquinone is added and reacted for 4 to 8 hours after stirring at room temperature for 10 to 20 hours, wherein the molar ratio of the precursor, potassium tert-butoxide and tetrachlorobenzoquinone is 1.0:80 to 86:80 to 86, and the solvent is removed under reduced pressure. The obtained crude product is further separated and purified by a silica gel column with an eluent to obtain the chichibabin-type luminescent diradical compound; the eluent is a mixture of dichloromethane and petroleum ether in a volume ratio of 1.0:2 to 5.

4. The method for preparing a chichibabin-type luminescent diradical compound as claimed in claim 3, characterized in that: The trityl carbon radical precursor is tris(2,4,6-trichlorophenyl)methane, (2,4,6-trichloro-3-pyridyl)bis(2,4,6-trichlorophenyl)methane or bis(2,4,6-trichloro-3-pyridyl)(2,4,6 trichlorophenyl)methane.

5. Use of a chichibabin-type luminescent diradical compound according to claim 1 or 2 in the preparation of biological imaging preparations or in the preparation of anti-tumor drugs.

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