Synthesis method of glucose-BODIPY diad and application of glucose-BODIPY diad in generation of superoxide anions and triplet-triplet annihilation up-conversion

Abstract

The invention relates to a synthesis method of a glucose and boron dipyrromethene diad and application of the glucose and boron dipyrromethene diad in generation of superoxide anions and triplet-triplet annihilation upconversion, which comprises the following steps: firstly, reacting hydroxyl boron dipyrromethene with acetyl bromide-alpha-D-glucose to obtain a compound 2, and further reacting with N-iodosuccinimide to obtain a compound 3; the preparation method comprises the following steps: carrying out a reaction on a compound 4 and trimethylsilylacetylene to obtain a compound 5, then reacting with 4-(diphenylamino) phenylboronic acid to obtain a molecule 4, then reacting with N-iodosuccinimide to obtain a compound 5, carrying out a Sonogashira coupling reaction on the compound 5 and trimethylsilylacetylene to obtain a compound 6, and finally, carrying out self-coupling under the catalysis of CuCl to obtain a molecule P-P. The superoxide anion generation capacity of the compound is measured, the compound is found to have excellent photooxidation capacity, 9, 10-bis (phenylethynyl) anthracene (BPEA) is taken as a receptor, a TTA up-conversion fluorescence spectrum of the compound is measured, and a result shows that the compound is expected to be applied to the field of triplet-triplet annihilation up-conversion.

Description

Technical Field

[0001] The present invention relates to the technical field of functional organic molecule design, synthesis and application, and in particular to a synthesis method of a glucose fluoroboron fluoride doublet and its application in generating superoxide anions and triplet-triplet annihilation upconversion. Background Art

[0002] Triplet-triplet annihilation upconversion (TTA upconversion) is a technology that converts low-energy (long-wavelength) light into high-energy (short-wavelength) light through a multi-photon mechanism. It has the advantages of low required excitation light energy, strong absorption capacity of photosensitizers, and easy control of absorption and emission wavelengths. (Li Y, Zhang J, Zhu S, et al. Efficient Red-to-Blue Triplet–Triplet Annihilation Upconversion Using the C70-Bodipy-Triphenylamine Triad as a Heavy-Atom-Free Triplet Photosensitizer[J]. The Journal of Physical Chemistry B, 2023, 127(39): 8476-8486.) Therefore, it can be widely used in solar cells, photocatalysis, intracellular fluorescence imaging, optoelectronic devices and other fields (Prabhakaran A, Jha KK, Sia RCE, et al. Triplet–Triplet Annihilation Upconverting Liposomes: Mechanistic Insights into the Role of Membranes in Two-Dimensional TTA-UC[J]. ACS Applied Materials&Interfaces, 2024).

[0003] Photodynamic therapy (PDT) has become a highly anticipated cancer treatment method. Under light conditions, the photosensitizer is converted into a singlet photosensitizer, which can return to the ground state through fluorescence emission, return to the ground state through non-radiative decay, or enter the triplet state through intersystem crossing (ISC), and undergo electron transfer in the triplet state, thereby further undergoing an oxidation reaction to generate superoxide anions, which can destroy tumor cells and achieve the effect of treating cancer (Luo X, Jiao Q, Pei S, et al. A Photoactivated Self-Assembled Nanoreactor for Inducing Cascade-Amplified Oxidative Stress toward Type I Photodynamic Therapy in Hypoxic Tumors [J]. Advanced Healthcare Materials, 2401787).

[0004] Boron difluorophosphate (BODIPY) has attracted the interest of the scientific community due to its wide application in fluorescence imaging, optoelectronic devices, and photodynamic therapy. BODIPY dyes have excellent photophysical properties and photostability, such as strong absorption in the visible light region, high molar extinction coefficient, and high fluorescence quantum yield (Lu H, Mack J, Nyokong T, et al. Optically active BODIPYs [J]. Coordination Chemistry Reviews, 2016, 318: 1-15). They can be modified to red-shift and change their phototherapy properties. Summary of the invention

[0005] In order to synthesize a photosensitizer with excellent superoxide anion generation and improve the efficiency of triplet-triplet annihilation upconversion of the photosensitizer, the present invention provides a synthesis method of a glucose fluoroboron fluorophore doublet and its application in generating superoxide anions and triplet-triplet annihilation upconversion.

[0006] In order to achieve the above object, the technical solution adopted by the present invention is:

[0007] First, the present invention proposes a method for synthesizing a glucose fluoroboron fluorophore dimer, and the synthesis route is:

[0008]

[0009] The synthesis method comprises the following steps in sequence:

[0010] Step a: Hydroxy BODIPY (compound 1) and acetyl bromide-α-D-glucose are dissolved in an organic solvent, and reacted in an alkaline environment of K2CO3 and under the catalysis of tetrabutylammonium bromide to generate compound 2, wherein the molar ratio of compound 1, acetyl bromide-α-D-glucose, K2CO3, and tetrabutylammonium bromide is 0.9-1.2:1.35-2.4:1.35-2.4:1.8-4.8, the reaction temperature is 60-70°C, and the reaction time is 3-6h;

[0011] Step b: Compound 2 and NIS are dissolved in an organic solvent and reacted to generate compound 3, the molar ratio of compound 2 to NIS is 0.9-1.2:0.6-0.9, the reaction temperature is 60-70° C., and the reaction time is 2-6 hours;

[0012] Step c: Compound 3, 4-(diphenylamino)phenylboronic acid and K2CO3 are dissolved in an organic solvent, and compound 4 is synthesized under the catalysis of Pd(PPh3)4, wherein the molar ratio of compound 3, 4-(diphenylamino)phenylboronic acid, K2CO3 and Pd(PPh3)4 is 0.9-1.2:1.4-1.8:2.7-3.6:0.05-0.07, the reaction temperature is 90-120°C, and the reaction time is 6-12h;

[0013] Step d: Compound 4 and NIS are dissolved in an organic solvent and reacted to generate compound 5, the molar ratio of compound 4 to NIS is 0.9-1.2:0.9-1.2, the reaction temperature is 60-70° C., and the reaction time is 2-4 h;

[0014] Step e: Compound 5, CuI, and PPh3 are dissolved in an organic solvent and Pd(PPh3)2Cl2 and TMSA are added under nitrogen protection to react for a period of time to generate compound 6, wherein compound 5, CuI 、 PpH 3、 Pd(PPh3)2Cl 2、 The molar ratio of TMSA is 0.9-1.2: 0.45-0.75: 0.45-0.75: 0.18-0.3: 9-20, the reaction temperature is 40-60°C, and the reaction time is 12-18h;

[0015] Step f: Compound 6 and CuCl are dissolved in an organic solvent to generate compound PP, wherein the molar ratio of compound 6 to CuCl is 0.9-1.2:3.6-6.0, the reaction temperature is 40-60° C., and the reaction time is 2-4 h.

[0016] As a preferred technical solution of the present invention, the specific operation of step a is: put hydroxy BODIPY, acetyl bromide-α-D-glucose, K2CO3, and tetrabutylammonium bromide into a single-mouth round-bottom flask, add CHCl3 / H2O mixed solvent, dissolve by ultrasound, react in a 60°C oil bath, and detect the reaction progress by TLC; after TLC shows that compound 1 completely disappears, stop the reaction; after cooling to room temperature, extract with water and dichloromethane, add anhydrous Na2SO4 to obtain the organic phase, dry for 0.5h, and remove the organic solvent by reduced pressure distillation to obtain a crude product, which is separated by silica gel column chromatography to obtain the product compound 2.

[0017] As the preferred technical solution of the present invention, the specific operation of step b is: putting compound 2 and NIS into a single-mouth round-bottom flask, adding CHCl3 / CH3COOH mixed solvent, ultrasonically dissolving, reacting in a 60°C oil bath, and detecting the reaction progress by TLC; after TLC shows that compound 2 completely disappears, stopping the reaction; after cooling to room temperature, extracting with saturated sodium thiosulfate and dichloromethane to remove CH3COOH, adding anhydrous Na2SO4 to the organic phase and drying for 2h, distilling under reduced pressure to remove the organic solvent to obtain a crude product, and separating by silica gel column chromatography to obtain the product compound 3.

[0018] As a preferred technical solution of the present invention, the specific operation of step c is: putting compound 3, 4-(diphenylamino)phenylboronic acid, and K2CO3 into a single-mouth round-bottom flask, adding a mixed solvent of toluene, ethanol, and water (v / v / v=8 / 1 / 1) and ultrasonically dissolving, continuously passing nitrogen for 10 to 20 minutes at room temperature, adding Pd(PPh3)4, passing nitrogen again for 10 to 20 minutes, vigorously stirring at 110°C for 12 hours, detecting the reaction progress by TLC, and after the reaction is completed, waiting for the mixture to be cooled to room temperature, extracting three times with saturated brine and dichloromethane, drying the organic phase with anhydrous Na2SO4, removing the solvent in vacuo, and re-dissolving with dichloromethane, separating by silica gel column chromatography to obtain compound 4.

[0019] As the preferred technical scheme of the present invention, the specific operation of step d is: put compound 4 and NIS into a single-mouth round-bottom flask, add CHCl3 / CH3COOH mixed solvent, dissolve by ultrasound, react in a 60°C oil bath, and detect the reaction progress by TLC; after TLC shows that compound 4 completely disappears, stop the reaction; after cooling to room temperature, extract with saturated sodium thiosulfate and dichloromethane to remove CH3COOH, add anhydrous Na2SO4 to obtain the organic phase and dry for 2h, remove the organic solvent by reduced pressure distillation to obtain a crude product, and separate by silica gel column chromatography to obtain the product compound 5.

[0020] As the preferred technical scheme of the present invention, the specific operation of step e is: put compound 5, CuI, and PPh3 into a single-mouth round-bottom flask, add Tol / Et3N mixed solvent, and dissolve under ultrasound; after nitrogen is introduced at room temperature for 10 to 20 minutes, Pd(PPh3)2Cl2 and TMSA are quickly added to the reaction system; nitrogen is removed after continuing to be introduced for 10 to 20 minutes, and the closed system is maintained to transfer the reaction to a 60°C oil bath, and the reaction progress is detected by TLC; the reaction is stopped after TLC shows that compound 5 has completely disappeared, and the reaction liquid is removed by reduced pressure distillation after the reaction is completed; the crude product is separated by column chromatography to obtain the product compound 6.

[0021] As a preferred technical solution of the present invention, the specific operation of step f is: putting compound 6 and CuCl into a single-mouth round-bottom flask and dissolving them in DMF solution, vigorously stirring at 60°C for 3 hours, and detecting the reaction progress by TLC. After the reaction is completed, extracting with water and dichloromethane three times, drying the organic phase with anhydrous Na2SO4 for 0.5h, removing the solvent under reduced pressure, re-dissolving with dichloromethane, and separating by silica gel column chromatography to obtain compound PP.

[0022] The glucose fluoroboron fluorophore synthesized by the present invention has excellent photooxidation ability by measuring its ability to generate superoxide anions, and its TTA upconversion fluorescence spectrum is measured using 9,10-bis(phenylethynyl)anthracene (BPEA) as an acceptor. The results show that it can be applied to the field of triplet-triplet annihilation upconversion. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 The target product PP of the present invention is 1 H NMR spectra.

[0024] Figure 2 The target product PP of the present invention is 13 C NMR spectrum.

[0025] Figure 3 It is the HRMS chart of the target product PP of the present invention.

[0026] Figure 4 This is a graph showing the fluorescence intensity of DHR123 oxidized by PP changing with time.

[0027] Figure 5 It is a line graph of I / I0 and illumination time of PP oxidation DHR123 at 526nm.

[0028] Figure 6 is the up-conversion fluorescence spectrum of PP with BPEA as the acceptor. DETAILED DESCRIPTION

[0029] Example 1

[0030] This example takes a glucose fluoroboron fluoride dimer PP as an example, and introduces its structure and specific synthesis method in combination with a synthesis route.

[0031] Step a, synthesis of compound 2:

[0032]

[0033] Weigh tetrabutylammonium bromide (190.0 mg, 0.610 mmol) into a 100 ml single-necked round-bottom flask and add 12 ml (v / v = 1 / 1) of CHCl3 / H2O mixed solvent, stir at 40 ° C for 10 min, weigh (250.0 mg, 0.610 mmol) of acetyl bromide-α-D-glucose, (165.8 mg, 1.200 mmol) of K2CO3, (120.0 mg, 0.350 mmol) of hydroxy BODIPY (compound 1) into the reaction solution, and add CHCl3 / H2O 20ml (v / v=1 / 1) of mixed solvent, raise the reaction temperature to 60°C and continue to stir vigorously for 6h, stop the reaction and wait for the mixture to cool to room temperature, extract with water and dichloromethane three times, dry the organic phase with anhydrous Na2SO4 and remove the solvent under reduced pressure, dissolve the resulting mixture in dichloromethane again, and purify the product by column chromatography using EA / PE (v / v=1 / 5) as eluent to obtain product 2 with a yield of 52% (122.6mg).

[0034] Compound 2 1 H NMR, 13 C NMR and HRMS spectrum analysis are as follows:

[0035] 1 H NMR (400MHz, CDCl3) δ7.21(d,J=8.0Hz,2H),7.11(d,J=8.0Hz,2H),5.98(s,2H),5.33-5.30(m,2H),5.19-5.13(m,2H),4.34-4. 30(m,1H),4.13-4.07(m,1H),3.94-3.89(m,1H),2.55(s,6H),2.09(s,3H),2,08(s,3H),2.06(s,3H),2.05(s,3H),1.40(s,6H).

[0036] 13C NMR (100MHz, CDCl3) δ170.62,170.36,169.54,169.40,157.47,157.70,143.11,141.02,131.69,130.03,129.54,121.40, 117.65,99.18,91.78,89.15,72.69,72.33,71.22,69.91,68.28,62.08,20.81,20.78,20.72,20.68,14.75,14.70,14.67.

[0037] HRMS(MALDI-TOF)m / z calcd for C 33 H 37 BF2N2O 10 [M +· ]670.2510,found,670.2517.

[0038] Step b, synthesis of compound 3:

[0039]

[0040] Weigh (201.1 mg, 0.300 mmol) of compound 2 and (51.8 mg, 0.230 mmol) of NIS into a 25 mL single-mouth round-bottom flask, add 8 ml of CHCl3 solution and 4 ml of CH3COOH solution and dissolve by ultrasound. Stir vigorously for 6 h at 60 ° C, monitor the reaction progress by TLC, and after the reaction is completed, cool the reaction solution to room temperature, extract it three times with saturated sodium thiosulfate and dichloromethane to remove CH3COOH, and add anhydrous Na2SO4 to the organic phase to dry for 2 h, remove the organic solvent by vacuum distillation, and redissolve it with dichloromethane, and separate it by silica gel column chromatography with CHCl2 / PE (v / v=1 / 5) as the eluent to obtain compound 3 with a yield of 44% (104.4 mg).

[0041] Compound 3 1 H NMR, 13 C NMR and HRMS spectrum analysis are as follows:

[0042] 1H NMR (400MHz, CDCl3) δ7.19(d,J=8.0Hz,2H),7.13(d,J=8.0Hz,2H),6.05(s,1H),5.34-5.31(m,2H),5.22-5.16(m,2H),4.35-4.30(m,1 H),4.21-4.17(m,1H),3.94-3.90(m,1H),2.62(s,3H),2.56(s,3H),2.10(s,3H),2,08(s,3H),2.06(s,3H),2.05(s,3H),1.41(s,6H).

[0043] 13 C NMR (100MHz, CDCl3) δ170.61,170.36,169.53,169.39,158.08,157.66,154.80,145.13,143.25,140.82,132.15,131.21,129.8 5,129.52,122.50,117.89,117.75,99.18,73.15,72.40,71.23,68.28,62.08,20.84,20.80,20.73,17.04,15.92,15.01,14.91.

[0044] HRMS(MALDI-TOF)m / z calcd for C 33 H 36 BF2IN2O 10 [M +· ]796.1476,found,796.1485.

[0045] Step c, synthesis of compound 4:

[0046]

[0047] Weigh (300.0 mg, 0.377 mmol) of compound 3, (163.0 mg, 0.564 mmol) of 4-(diphenylamino)phenylboronic acid, and (155.4 mg, 1.125 mmol) of K2CO3 into a 100 ml single-necked round-bottom flask, add 20 ml of a mixed solvent of toluene, ethanol, and water (v / v / v=8 / 1 / 1) and dissolve by ultrasonication, continue to introduce nitrogen at room temperature for 20 min, add (26.0 mg, 0.023 mmol)Pd(PPh3)4, nitrogen was introduced again for 10 min, the mixture was vigorously stirred at 110°C for 12 h, and the reaction progress was monitored by TLC. After the reaction was completed, the mixture was cooled to room temperature, extracted three times with saturated brine and dichloromethane, the organic phase was dried over anhydrous Na2SO4, the solvent was removed in vacuo, and it was redissolved in dichloromethane, and separated by silica gel column chromatography with EA / PE (v / v=1 / 5) as eluent to obtain compound 4 with a yield of 63% (215.9 mg).

[0048] Compound 4 1 H NMR, 13 C NMR and HRMS spectrum analysis are as follows:

[0049] 1 H NMR (400MHz, CDCl3) δ7.28-7.24(m,6H),7.14-7.10(m,6H),7.07-6.97(m,6H),6.00(s,1H),5.36-5.29(m,2H),5.21-5.14(m,2H),4.34-4.3 0(m,1H),4.20-4.17(m,1H),3.93-3.89(m,1H),2.57(s,3H),2.55(s, 3H),2.09(s,3H),2,08(s,3H),2.06(s,3H),2.05(s,3H),1.26(s,6H).

[0050] 13 C NMR (100MHz, CDCl3) δ170.65,170.35,169.52,169.41,157.53,155.59,154. 77,147.73,146.89,142.94,141.02,139.12,133.62,130.92,130.36,129.6 5,129.42,127.26,124.69,123.17,123.07,121.43,117.69,99.28,72.72,72.38,71.25,68,30,62.10,20.85,20.81,20.74,14.85,14.27,13.63,13.26.

[0051] HRMS(MALDI-TOF)m / z calcd for C 51 H 50 BF2N3O 10 [M+·]913.3560,found,913.3759.

[0052] Step d, synthesis of compound 5:

[0053]

[0054] Weigh (274.0 mg, 0.300 mmol) of compound 4 and (81.0 mg, 0.360 mmol) of NIS into a 25 mL single-mouth round-bottom flask, add 8 ml of CHCl3 solution and 4 ml of CH3COOH solution and dissolve by ultrasonication. Place the reaction in a 60 ° C oil bath, monitor the reaction progress by TLC, and the reaction is complete after 3 hours. After cooling to room temperature, extract with saturated sodium thiosulfate and dichloromethane three times to remove CH3COOH, and add anhydrous Na2SO4 to the organic phase to dry for 0.5 hours, remove the organic solvent by vacuum distillation, and redissolve with dichloromethane, separate by silica gel column chromatography with CHCl2 / PE (v / v=1 / 3), and obtain compound 5 with a yield of 88% (274.3 mg).

[0055] Compound 5 1 H NMR, 13 C NMR and HRMS spectrum analysis are as follows:

[0056] 1 H NMR (400MHz, CDCl3) δ7.28-7.22(m,6H),7.15-7.10(m,6H),7.07-7.02(m,4H),6.97(d,J=8Hz,2H),5.36-5.29(m,2H),5.22-5.15(m,2H),4.35- 4.30(m,1H),4.21-4.17(m,1H),3.94-3.89(m,1H),2.65(s,3H),2.55(s ,3H),2.09(s,3H),2,08(s,3H),2.06(s,3H),2.05(s,3H),1.43(s,6H).

[0057] 13C NMR (100MHz, CDCl3) δ170.60,170.35,169.52,169.38,157.73,157.39,154.63, 147.67,147.22,142.97,140.76,134.79,131.93,131.40,130.84,130.22,129.6 4,129.47,126.60,124.82,123.32,122.94,117.98,117.85,99.30,72.74,72.46,71.29,68.34,62.11,22.83,20.84,20.79,20.73,17.12,15.95,14.25,13.49.

[0058] HRMS(MALDI-TOF)m / z calcd for C 51 H 49 BF2IN3O 10 [M+·]1039.2527,found,1039.2538.

[0059] Step e, synthesis of compound 6:

[0060]

[0061] Weigh (98.0 mg, 0.094 mmol) of compound 5, (9.0 mg, 0.047 mmol) of CuI, and (12.3 mg, 0.047 mmol) of PPh3 into a 25 ml single-necked round-bottom flask, add 5 ml of THF solution and 15 ml of Et3N solution, and dissolve under ultrasound; after nitrogen is introduced at room temperature for 20 min, (13.2 mg, 0.019 mmol) of Pd(PPh3)2Cl2 and 184.7 mg (1.880 mmol) of TMSA are added to the reaction system; nitrogen is continued to be introduced for 10 min and then removed, and the mixture is stirred at 60 ° C for 12 h, and the reaction progress is monitored by TLC. After the reaction is completed, the reaction solution is removed and redissolved with dichloromethane, and separated by silica gel column chromatography with EA / PE (v / v=1 / 4) to obtain compound 6 with a yield of 66% (62.7 mg).

[0062] Compound 6 1 H NMR, 13 C NMR and HRMS spectrum analysis are as follows:

[0063] 1H NMR (400MHz, CDCl3) δ7.28-7.21(m,6H),7.14-7.10(m,6H),7.07-7.01(m,4H), 6.96(d,J=8.0Hz,2H),5.36-5.29(m,2H),5.22-5.14(m,2H),4.35-4.30(m,1H) ,4.21-4.17(m,1H),3.94-3.89(m,1H),2.64(s,3H),2.56(s,3H),2.09(s,3H), 2,08(s,3H),2.06(s,3H),2.05(s,3H),1.48(s,3H),1.37(s,3H),0.21(s,9H).

[0064] 13 C NMR (100MHz, CDCl3) δ170.63,170.37,169.54,169.40,157.68,157.19,156.98,147 .65,147.15,143.14,141.39,140.39,134.27,130.83,130.03,129.59,129.45,128 .54,126.63,124.79,123.29,122.93,117.89,101.23,99.27,97.68,72.72,72.41,71.25,68.31,62.11,20.84,20.80,20.75,20.73,14.26,13.82,13.61,13.44,0.27.

[0065] HRMS(MALDI-TOF)m / z calcd for C 56 H 58 BF2IN3O 10 Si[M+·]1009.3957,found,1009.3969.

[0066] Step f, synthesis of compound PP:

[0067]

[0068] Weigh (101.0 mg, 0.100 mmol) of compound 6 and (50.0 mg, 0.505 mmol) of CuCl into a 25 ml single-necked round-bottom flask and dissolve in 5 ml of DMF solution. Stir vigorously at 60 °C for 3 h, and monitor the progress of the reaction by TLC. After the reaction is completed, extract with water and dichloromethane three times. Dry the organic phase with anhydrous Na2SO4 for 0.5 h, remove the solvent under reduced pressure, redissolve with dichloromethane, and separate by silica gel column chromatography with MeOH / CH2Cl2 (v / v=1 / 100) to obtain compound PP with a yield of 67% (125.4 mg).

[0069] The target product PP 1 H NMR, 13 C NMR and HRMS diagrams are shown in Figure 1 , 2 , 3, the spectrum analysis is as follows:

[0070] 1 H NMR (400MHz, CDCl3) δ7.28-7.22(m,12H),7.15-7.10(m,12H),7.07-7.02(m ,8H),6.96(d,J=8.0Hz,4H),5.35-5.29(m,4H),5.22-5.16(m,4H),4.35-4.3 2(m,2H),4.20-4.17(m,2H),3.93-3.90(m,2H),2.67(s,6H),2.56(s,6H),2. 09(s,6H),2,08(s,6H),2.06(s,6H),2.05(s,6H),1.50(s,6H),1.37(s,6H).

[0071] 13 C NMR (100MHz, CDCl3) δ170.63,170.36,169.55,169.41,158.28,157.70,147.61, 147.25,143.50,141.36,140.92,135.01,132.96,130.79,130.27,129.46,126. 33,124.82,123.34,122.86,117.98,117.74,113.86,99.23,80.37,75.72,72.69,72.41,71.22,68.26,62.05,20.86,20.81,20.74,14.26,13.78,13.66,13.51.

[0072] HRMS(MALDI-TOF)m / z calcd for C106 H 98 BF4N6O 20 Si[M+·]1872.6961,found,1872.7007.

[0073] Example 2

[0074] In order to detect the ability of PP to generate superoxide anions, the present invention uses dihydrorhodamine 123 (DHR123) as a chemical sensor. Under light, PP will generate superoxide anions to oxidize dihydrorhodamine 123, so that it changes from colorless and transparent dihydrorhodamine to rhodamine 123 with green fluorescence, so that its fluorescence intensity at 526nm increases. According to the change of fluorescence intensity, the ability of PP to generate superoxide anions is evaluated. The fluorescence intensity curve of PP oxidizing DHR123 over time is shown in FIG. Figure 4 Specific experimental steps:

[0075] Compound PP was prepared with DMSO / deionized water (1 / 49, v / v) to a concentration of 1 x 10 -5 mol / L concentration, and further prepared the solution to contain 1x 10 -5 mol / L DHR123 concentration of the test solution, transfer the specified volume of the test solution to the fluorescent dish, and use 10mW / cm 2 The cells were irradiated with white light for 10 s each and repeated for ten cycles. The rise in fluorescence intensity at 526 nm was recorded using a fluorescence spectrophotometer to detect the amount of DHR123 consumed by oxidation.

[0076] Figure 4 The fluorescence intensity at 526 nm increased significantly over time, indicating that PP has an excellent ability to generate superoxide anions. Figure 5 Fluorescence intensity data at 526 nm were collected to obtain a line graph of the fluorescence intensity I / I0 of PP as time went by. The fluorescence intensity ratio increased steadily over time, indicating that PP had the ability to stably generate superoxide anions.

[0077] In order to verify whether PP is expected to be applied to triplet-triplet annihilation upconversion, the present invention measured the upconversion fluorescence spectrum of PP, 9,10-bis(phenylethynyl)anthracene (BPEA) was used as the acceptor, and strong red fluorescence was observed in deoxygenated chloroform under excitation at 532nm. Figure 6 The fluorescence emission spectrum of TTA at a concentration of 10 mM BPEA. Specific experimental steps:

[0078] A semiconductor laser (532nm) was selected as the excitation light source. The laser spot diameter in the sample cell area was 3.5mm. In the upconversion experiment, the mixed solution of the photosensitizer and the acceptor was stored in a temperature-controlled quartz tube (10mm x 3mm) and deoxygenated with high-purity argon gas for at least 20 minutes, and the gas flow was maintained during the measurement. A commercial fiber optic spectrometer was used to collect and detect the upconversion fluorescence of the acceptor.

[0079] Figure 6 The upconversion fluorescence covers a wavelength range of 480 to 520 nm, which is the same as the fluorescence of BPEA itself, indicating that PP supports the occurrence of photon upconversion and is expected to be applied in triplet-triplet annihilation upconversion.

[0080] The above contents are merely examples and explanations of the concept of the present invention. The technicians in this technical field may make various modifications or additions to the specific embodiments described or replace them in a similar manner. As long as they do not deviate from the concept of the invention or exceed the scope defined by the claims, they should all fall within the protection scope of the present invention.

Claims

1. A method for synthesizing a glucose fluorine boron fluoride dyad, characterized in that: The synthetic route is: The synthesis method comprises the following steps in sequence: Step a: Hydroxy BODIPY (compound 1) and acetyl bromide-α-D-glucose are dissolved in an organic solvent, and reacted in an alkaline environment of K2CO3 and under the catalysis of tetrabutylammonium bromide to generate compound 2, wherein the molar ratio of compound 1, acetyl bromide-α-D-glucose, K2CO3, and tetrabutylammonium bromide is 0.9-1.2:1.35-2.4:1.35-2.4:1.8-4.8, the reaction temperature is 60-70°C, and the reaction time is 3-6h; Step b: Compound 2 and NIS are dissolved in an organic solvent and reacted to generate compound 3, the molar ratio of compound 2 to NIS is 0.9-1.2:0.6-0.9, the reaction temperature is 60-70° C., and the reaction time is 2-6 hours; Step c: Compound 3, 4-(diphenylamino)phenylboronic acid and K2CO3 are dissolved in an organic solvent, and compound 4 is synthesized under the catalysis of Pd(PPh3)4, wherein the molar ratio of compound 3, 4-(diphenylamino)phenylboronic acid, K2CO3 and Pd(PPh3)4 is 0.9-1.2:1.4-1.8:2.7-3.6:0.05-0.07, the reaction temperature is 90-120°C, and the reaction time is 6-12h; Step d: Compound 4 and NIS are dissolved in an organic solvent and reacted to generate compound 5, the molar ratio of compound 4 to NIS is 0.9-1.2:0.9-1.2, the reaction temperature is 60-70° C., and the reaction time is 2-4 h; Step e: Compound 5, CuI, and PPh3 are dissolved in an organic solvent and Pd(PPh3)2Cl2 and TMSA are added under nitrogen protection to react for a period of time to generate compound 6, wherein compound 5, CuI, and PPh 3、 The molar ratio of Pd(PPh3)2Cl2TMS is 0.9-1.2:0.45-0.75:0.45-0.75:0.18-0.3:9-20, the reaction temperature is 40-60°C, and the reaction time is 12-18h; Step f: Compound 6 and CuCl are dissolved in an organic solvent to generate compound PP, wherein the molar ratio of compound 6 to CuCl is 0.9-1.2:3.6-6.0, the reaction temperature is 40-60° C., and the reaction time is 2-4 h.

2. The synthesis method according to claim 1, characterized in that The specific operation of step a is as follows: put hydroxy BODIPY, acetyl bromide-α-D-glucose, K2CO3, and tetrabutylammonium bromide into a single-mouth round-bottom flask, add a CHCl3 / H2O mixed solvent, dissolve by ultrasonication, react in an oil bath at 60°C, and detect the reaction progress by TLC; stop the reaction after TLC shows that compound 1 completely disappears; cool to room temperature, extract with water and dichloromethane, add anhydrous Na2SO4 to obtain the organic phase, dry for 0.5h, remove the organic solvent by reduced pressure distillation to obtain a crude product, and separate by silica gel column chromatography to obtain the product compound 2.

3. The synthesis method according to claim 1, characterized in that The specific operation of step b is as follows: putting compound 2 and NIS into a single-mouth round-bottom flask, adding a CHCl3 / CH3COOH mixed solvent, dissolving by ultrasonication, reacting in an oil bath at 60°C, and detecting the reaction progress by TLC; stopping the reaction after TLC shows that compound 2 completely disappears; cooling to room temperature, extracting with saturated sodium thiosulfate and dichloromethane to remove CH3COOH, adding anhydrous Na2SO4 to the obtained organic phase and drying for 2h, distilling under reduced pressure to remove the organic solvent to obtain a crude product, and separating by silica gel column chromatography to obtain the product compound 3.

4. The synthesis method according to claim 1, characterized in that The specific operation of step c is: put compound 3, 4-(diphenylamino)phenylboronic acid and K2CO3 into a single-mouth round-bottom flask, add a mixed solvent of toluene, ethanol and water (v / v / v=8 / 1 / 1) and ultrasonically dissolve, continue to introduce nitrogen for 10 to 20 minutes at room temperature, add Pd(PPh3)4, introduce nitrogen again for 10 to 20 minutes, vigorously stir at 110°C for 12 hours, monitor the reaction progress by TLC, and after the reaction is completed, cool the mixture to room temperature, extract it three times with saturated brine and dichloromethane, dry the organic phase with anhydrous Na2SO4, remove the solvent in vacuo, and redissolve it with dichloromethane, separate it by silica gel column chromatography, and obtain compound 4.

5. The synthesis method according to claim 1, characterized in that The specific operation of step d is as follows: Compound 4 and NIS are put into a single-mouth round-bottom flask, a CHCl3 / CH3COOH mixed solvent is added, the mixture is dissolved by ultrasonication, the mixture is reacted in an oil bath at 60°C, and the reaction progress is detected by TLC; after TLC shows that compound 4 completely disappears, the reaction is stopped; after cooling to room temperature, the mixture is extracted with saturated sodium thiosulfate and dichloromethane to remove CH3COOH, anhydrous Na2SO4 is added to the obtained organic phase, and the mixture is dried for 2h, and the organic solvent is removed by vacuum distillation to obtain a crude product, which is separated by silica gel column chromatography to obtain the product compound 5.

6. The synthesis method according to claim 1, characterized in that The specific operation of step e is as follows: Compound 5, CuI, and PPh3 are put into a single-mouth round-bottom flask, a Tol / Et3N mixed solvent is added, and the mixture is dissolved under ultrasound; after nitrogen is introduced at room temperature for 10 to 20 minutes, Pd(PPh3)2Cl2 and TMSA are quickly added to the reaction system; nitrogen is introduced for 10 to 20 minutes and then removed, the reaction is transferred to a 60°C oil bath while maintaining a closed system, and the reaction progress is monitored by TLC; the reaction is stopped after TLC shows that compound 5 has completely disappeared, and the reaction solution is removed by reduced pressure distillation after the reaction is completed; the crude product is separated by column chromatography to obtain the product compound 6.

7. The synthesis method according to claim 1, characterized in that The specific operation of step f is as follows: compound 6 and CuCl are put into a single-mouth round-bottom flask and dissolved in a DMF solution, vigorously stirred at 60° C. for 3 h, and the reaction progress is detected by TLC. After the reaction is completed, the mixture is extracted three times with water and dichloromethane, and the organic phase is dried with anhydrous Na2SO4 for 0.5 h. The solvent is removed under reduced pressure, and the mixture is redissolved with dichloromethane. The mixture is separated by silica gel column chromatography to obtain compound PP.

8. Use of the glucose fluoroboron fluoride dyad synthesized by the method according to any one of claims 1 to 7 in the generation of superoxide anions and triplet-triplet annihilation upconversion.

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