PH reversibly activated near-infrared two-region aggregation-induced emission type I photosensitizer and application thereof

Abstract

The invention discloses a pH reversibly activated near-infrared two-region aggregation-induced emission type I photosensitizer and application thereof, the pH reversibly activated near-infrared two-region aggregation-induced emission type I photosensitizer is one of the following chemical structural formulas: R1 and R2 are selected from one of hydrogen, methyl and methoxyl, and R3 is selected from one of hydrogen, methyl and methoxyl. The pH reversibly activated near-infrared two-region aggregation-induced emission type I photosensitizer provided by the invention has the following advantages: the phototoxicity to normal tissues and cells is low, and the photosensitizer has very excellent tumor cell targeting ability; the fluorescent probe gathers in a physiological environment, but does not have the problem of fluorescence quenching, and the active oxygen generation ability is enhanced; according to the present invention, with the application of the nano-material, the prepared nano-material has the deep tissue penetration ability under the excitation of near-infrared light, and has the good photo-thermal and photodynamic synergistic treatment effect on the human-derived tumor xenograft (PDX) model and the bacterial infection, such that the prepared nano-material has the good photo-thermal and photodynamic synergistic treatment effect on the human-derived tumor xenograft (PDX) model and the bacterial infection.

Description

technical field

[0001] The invention relates to the technical field of photosensitizers, in particular to a pH reversibly activated near-infrared second region aggregation-induced luminescence type I photosensitizer and applications thereof. Background technique

[0002] Photodynamic therapy (PDT) and photothermal synergistic therapy (PTT) have emerged in recent years as a highly effective treatment for malignant tumors. Compared with traditional chemotherapy and radiotherapy, due to their non-invasive, low drug resistance and The advantages of controllable treatment area selection and other advantages have attracted extensive attention of medical researchers. PDT usually consists of three parts: photosensitizer, light and oxygen, all three are indispensable. Under the excitation light source of a specific wavelength, the photosensitizer absorbs a photon, and then from the ground state (S 0 ) transitions to the singlet excited state (S 1 ). The excited state of the molec...

Examples

Embodiment 1

[0056] like figure 1 shown in a, in N 2 under the protection of The reaction was continuously stirred for 3 h, and extracted with ethyl acetate after the reaction was completed. The organic phases were combined and dried with anhydrous sodium sulfate. After concentration under reduced pressure, the residue obtained was washed with petroleum ether / ethyl acetate (100:1→10:1). The removal agent was purified by silica gel column chromatography to obtain 1.20 g of yellow powdery solid compound 1 in a yield of 52%. The hydrogen nuclear magnetic resonance spectrum of the compound 1 in deuterated chloroform is as follows figure 2 As shown, the carbon nuclear magnetic resonance spectrum of the compound 1 in deuterated chloroform is as follows image 3 shown, where, 1 H NMR (600MHz, CDCl 3 )δ8.04(d,J=6.6Hz,1H),7.98(d,J=8.4Hz,1H),7.68(dd,J 1 =7.8Hz,J 2 =6.6Hz,1H),7.50(d,J=8.4Hz,1H),7.44(dd,J 1 =8.4Hz,J 2 =7.2Hz,1H),6.89(d,J=6.6Hz,1H),3.97(q,J=7.2Hz,2H),1.37(t,J=7.2Hz,3H). 13 C...

Embodiment 2

[0058] like figure 1 shown in a, in N 2 Under the protection of , 1.20g of compound 1 was dissolved in 25ml of dry tetrahydrofuran solution, and then 2.43ml of 3.0M methylmagnesium chloride solution was added dropwise to the above reaction solution. After dropping, the reaction was stirred at 60 °C for 1 h, and the reaction solution was cooled After reaching room temperature, 12.16 ml of 2M hydrochloric acid solution was added, and the tetrahydrofuran was removed by concentration under reduced pressure, then 6.08 ml of 1M potassium iodide solution was added, and a large amount of red precipitates were precipitated by continuing the stirring reaction for 30 min. After filtration, the obtained solid was washed with water and ethyl acetate successively, and dried to obtain 1.52 g of crude compound 2 as a red solid powder with a yield of 70%. The hydrogen nuclear magnetic resonance spectrum of the compound 2 in dimethyl sulfoxide is as follows Figure 4 shown, where, 1 H NMR (6...

Embodiment 3

[0060] like figure 1 shown in b, in N 2 Under the protection of the 2 (dba) 3 and 274 mg of tri-tert-butylphosphine tetrafluoroborate. Then the reaction solution was heated to 120 °C in an oil bath for 16 h. After cooling to room temperature, the solvent was concentrated under reduced pressure to remove the solvent, and the obtained residue was purified by silica gel column chromatography using petroleum ether / ethyl acetate (200:1→50:1) as eluent to obtain 4.20g of yellow powdery solid compound 4, Yield 71%. The hydrogen nuclear magnetic resonance spectrum of the compound 4 in deuterated chloroform is as follows Figure 5 As shown, the carbon nuclear magnetic resonance spectrum of the compound 4 in deuterated chloroform is as follows Image 6 shown, where, 1 H NMR (400MHz, Methylene Chloride-d 2 )δ7.29(d,J=5.2Hz,2H),7.26(d,J=5.2Hz,2H),7.14(dd,J 1 =8.8Hz,J 2 =1.2Hz,4H),7.05–7.01(m,3H),6.91(dd,J 1 =5.6Hz,J 2 =5.2Hz,1H),6.74(dd,J 1 =1.2Hz,J 2 =3.6Hz,1H). 13 CNMR (1...

technical field

[0001] The invention relates to the technical field of photosensitizers, in particular to a pH reversibly activated near-infrared second region aggregation-induced luminescence type I photosensitizer and applications thereof. Background technique

[0002] Photodynamic therapy (PDT) and photothermal synergistic therapy (PTT) have emerged in recent years as a highly effective treatment for malignant tumors. Compared with traditional chemotherapy and radiotherapy, due to their non-invasive, low drug resistance and The advantages of controllable treatment area selection and other advantages have attracted extensive attention of medical researchers. PDT usually consists of three parts: photosensitizer, light and oxygen, all three are indispensable. Under the excitation light source of a specific wavelength, the photosensitizer absorbs a photon, and then from the ground state (S 0 ) transitions to the singlet excited state (S 1 ). The excited state of the molec...

Examples

Embodiment 1

[0056] like figure 1 shown in a, in N 2 under the protection of The reaction was continuously stirred for 3 h, and extracted with ethyl acetate after the reaction was completed. The organic phases were combined and dried with anhydrous sodium sulfate. After concentration under reduced pressure, the residue obtained was washed with petroleum ether / ethyl acetate (100:1→10:1). The removal agent was purified by silica gel column chromatography to obtain 1.20 g of yellow powdery solid compound 1 in a yield of 52%. The hydrogen nuclear magnetic resonance spectrum of the compound 1 in deuterated chloroform is as follows figure 2 As shown, the carbon nuclear magnetic resonance spectrum of the compound 1 in deuterated chloroform is as follows image 3 shown, where, 1 H NMR (600MHz, CDCl 3 )δ8.04(d,J=6.6Hz,1H),7.98(d,J=8.4Hz,1H),7.68(dd,J 1 =7.8Hz,J 2 =6.6Hz,1H),7.50(d,J=8.4Hz,1H),7.44(dd,J 1 =8.4Hz,J 2 =7.2Hz,1H),6.89(d,J=6.6Hz,1H),3.97(q,J=7.2Hz,2H),1.37(t,J=7.2Hz,3H). 13 C...

Embodiment 2

[0058] like figure 1 shown in a, in N 2 Under the protection of , 1.20g of compound 1 was dissolved in 25ml of dry tetrahydrofuran solution, and then 2.43ml of 3.0M methylmagnesium chloride solution was added dropwise to the above reaction solution. After dropping, the reaction was stirred at 60 °C for 1 h, and the reaction solution was cooled After reaching room temperature, 12.16 ml of 2M hydrochloric acid solution was added, and the tetrahydrofuran was removed by concentration under reduced pressure, then 6.08 ml of 1M potassium iodide solution was added, and a large amount of red precipitates were precipitated by continuing the stirring reaction for 30 min. After filtration, the obtained solid was washed with water and ethyl acetate successively, and dried to obtain 1.52 g of crude compound 2 as a red solid powder with a yield of 70%. The hydrogen nuclear magnetic resonance spectrum of the compound 2 in dimethyl sulfoxide is as follows Figure 4 shown, where, 1 H NMR (6...

Embodiment 3

[0060] like figure 1 shown in b, in N 2 Under the protection of the 2 (dba) 3 and 274 mg of tri-tert-butylphosphine tetrafluoroborate. Then the reaction solution was heated to 120 °C in an oil bath for 16 h. After cooling to room temperature, the solvent was concentrated under reduced pressure to remove the solvent, and the obtained residue was purified by silica gel column chromatography using petroleum ether / ethyl acetate (200:1→50:1) as eluent to obtain 4.20g of yellow powdery solid compound 4, Yield 71%. The hydrogen nuclear magnetic resonance spectrum of the compound 4 in deuterated chloroform is as follows Figure 5 As shown, the carbon nuclear magnetic resonance spectrum of the compound 4 in deuterated chloroform is as follows Image 6 shown, where, 1 H NMR (400MHz, Methylene Chloride-d 2 )δ7.29(d,J=5.2Hz,2H),7.26(d,J=5.2Hz,2H),7.14(dd,J 1 =8.8Hz,J 2 =1.2Hz,4H),7.05–7.01(m,3H),6.91(dd,J 1 =5.6Hz,J 2 =5.2Hz,1H),6.74(dd,J 1 =1.2Hz,J 2 =3.6Hz,1H). 13 CNMR (1...

Images