Near-infrared two-window fluorescence probe based on Aza-BODIPY, as well as preparation and application thereof

Abstract

The invention relates to design synthesis and application of a near-infrared two-window fluorescence probe based on Aza-BODIPY, and belongs to the field of organic fluorescence probes. A near-infraredtwo-area dyestuff (NIR-II, 1000-1700nm) has a long emission wavelength and less light scattering and tissue autofluorescence interference so as to obtain better resolution ratio and imaging depth inbioimaging. An Aza-BODIPY fluorescent dye has a longer absorption emission wavelength, a narrower peak width at half height and a larger molar extinction coefficient, and is widely applied to the fields such as photodynamic therapy. The structural formula of the near-infrared two-window fluorescence probe designed and synthesized by the invention is as shown in the figure (I). According to the probe, electron-donating group julolidine is introduced onto the classic Aza-BODIPY structure, and the molecular rigidity is improved. The probe has excellent light stability and a capacity of resistingdisturbance. The probe successfully realizes near-infrared two-window imaging during the mice imaging experiment.

Description

technical field

[0001] The invention relates to a fluorescent probe with two near-infrared windows based on Aza-BODIPY, its preparation and application, and belongs to the field of organic fluorescent probes. Background technique

[0002] Fluorescence imaging provides a powerful tool for biological research and biomedical applications, compared to currently applied imaging techniques such as magnetic resonance (MRI), tomography (CT), ultrasound (Ultrasound), positron emission tomography (PET), single photon emission computed tomography (SPECT), photoacoustic tomography (PAT), etc. Fluorescence imaging (FLI) technology has the advantages of multi-channel imaging, fast response time, simple operation, and low price. In particular, fluorescence imaging has a high signal-to-noise ratio, low toxicity, and can meet many requirements in medical imaging, so it has received great attention.

[0003] Dyes and probes used in bioluminescent imaging often need to meet requirements in fo...

Examples

Embodiment 1

[0050] The preparation method of a series of Aza-BODIPY-based near-infrared two-window fluorescent probe FBL3 is as follows:

[0051] 1.1 1: Phosphorus oxychloride (1.17g, 7.62mmol) was slowly added dropwise to a round-bottomed flask containing DMF (1.67g, 22.87mmol) in an ice-salt bath, and the ice bath was removed after the addition was completed. Under the protection of nitrogen, continue stirring at room temperature for half an hour to prepare the Vilsmeier-Haack reagent. Then, the DMF solution dissolved with julonidine (1.2 g, 6.93 mmol) was slowly added dropwise thereto, and after the dropwise addition was completed, it was refluxed at 90° C. for 4 h. The reacted substance was poured into ice water to stop the reaction, and the stirring was continued for at least 2 h, a yellow solid was precipitated, and finally a light yellow solid 1 was obtained by suction filtration. 1 H NMR (300MHz, CDCl3) δ9.59(s,1H),7.28(s,2H),3.28(t,J=6.0,4H),2.76(t,J=6.0,4H),1.95(m,4H ). Its r...

Embodiment 2

[0060] The preparation method of a series of Aza-BODIPY-based near-infrared two-window fluorescent probe FBL3 is as follows:

[0061] 2.1 1: Phosphorus oxychloride (2.34g, 15.24mmol) was slowly added dropwise to a round-bottomed flask containing DMF (3.34g, 45.74mmol) in an ice-salt bath, and the ice bath was removed after the addition was completed. Under the protection of nitrogen, continue stirring at room temperature for half an hour to prepare the Vilsmeier-Haack reagent. Then, the DMF solution dissolved with julonidine (2 g, 11.55 mmol) was slowly added dropwise thereto, and after the dropwise addition was completed, it was refluxed at 90° C. for 4 h. The reacted substance was poured into ice water to stop the reaction, and the stirring was continued for at least 2 h, a yellow solid was precipitated, and finally a light yellow solid 1 was obtained by suction filtration.

[0062] 2.2 10: Add methoxyacetophenone (751mg, 5mmol), compound 1 (800mg, 3.94mmol), ethanol (60mL)...

Embodiment 3

[0066] The preparation method of the series based on Aza-BODIPY-based near-infrared two-window fluorescent probe FBL3 is as follows:

[0067] 3.1 1: Phosphorus oxychloride (0.585g, 3.81mmol) was slowly added dropwise to a round-bottomed flask containing DMF (1g, 13.72mmol) in an ice-salt bath, and the ice bath was removed after the addition was completed. Under nitrogen protection, continue stirring at room temperature for half an hour to prepare Vilsmeier-Haack reagent. Then a DMF solution in which julolidine (0.6 g, 3.46 mmol) was dissolved was slowly added dropwise thereto, and after the dropwise addition was completed, it was refluxed at 90° C. for 4 h. The reacted substance was poured into ice water to stop the reaction, and the stirring was continued for at least 2 h, a yellow solid was precipitated, and finally a light yellow solid 1 was obtained by suction filtration.

[0068]3.2 10: Add methoxyacetophenone (375.5mg, 2.5mmol), compound 1 (300mg, 1.476mmol), ethanol (3...

technical field

[0001] The invention relates to a fluorescent probe with two near-infrared windows based on Aza-BODIPY, its preparation and application, and belongs to the field of organic fluorescent probes. Background technique

[0002] Fluorescence imaging provides a powerful tool for biological research and biomedical applications, compared to currently applied imaging techniques such as magnetic resonance (MRI), tomography (CT), ultrasound (Ultrasound), positron emission tomography (PET), single photon emission computed tomography (SPECT), photoacoustic tomography (PAT), etc. Fluorescence imaging (FLI) technology has the advantages of multi-channel imaging, fast response time, simple operation, and low price. In particular, fluorescence imaging has a high signal-to-noise ratio, low toxicity, and can meet many requirements in medical imaging, so it has received great attention.

[0003] Dyes and probes used in bioluminescent imaging often need to meet requirements in fo...

Examples

Embodiment 1

[0050] The preparation method of a series of Aza-BODIPY-based near-infrared two-window fluorescent probe FBL3 is as follows:

[0051] 1.1 1: Phosphorus oxychloride (1.17g, 7.62mmol) was slowly added dropwise to a round-bottomed flask containing DMF (1.67g, 22.87mmol) in an ice-salt bath, and the ice bath was removed after the addition was completed. Under the protection of nitrogen, continue stirring at room temperature for half an hour to prepare the Vilsmeier-Haack reagent. Then, the DMF solution dissolved with julonidine (1.2 g, 6.93 mmol) was slowly added dropwise thereto, and after the dropwise addition was completed, it was refluxed at 90° C. for 4 h. The reacted substance was poured into ice water to stop the reaction, and the stirring was continued for at least 2 h, a yellow solid was precipitated, and finally a light yellow solid 1 was obtained by suction filtration. 1 H NMR (300MHz, CDCl3) δ9.59(s,1H),7.28(s,2H),3.28(t,J=6.0,4H),2.76(t,J=6.0,4H),1.95(m,4H ). Its r...

Embodiment 2

[0060] The preparation method of a series of Aza-BODIPY-based near-infrared two-window fluorescent probe FBL3 is as follows:

[0061] 2.1 1: Phosphorus oxychloride (2.34g, 15.24mmol) was slowly added dropwise to a round-bottomed flask containing DMF (3.34g, 45.74mmol) in an ice-salt bath, and the ice bath was removed after the addition was completed. Under the protection of nitrogen, continue stirring at room temperature for half an hour to prepare the Vilsmeier-Haack reagent. Then, the DMF solution dissolved with julonidine (2 g, 11.55 mmol) was slowly added dropwise thereto, and after the dropwise addition was completed, it was refluxed at 90° C. for 4 h. The reacted substance was poured into ice water to stop the reaction, and the stirring was continued for at least 2 h, a yellow solid was precipitated, and finally a light yellow solid 1 was obtained by suction filtration.

[0062] 2.2 10: Add methoxyacetophenone (751mg, 5mmol), compound 1 (800mg, 3.94mmol), ethanol (60mL)...

Embodiment 3

[0066] The preparation method of the series based on Aza-BODIPY-based near-infrared two-window fluorescent probe FBL3 is as follows:

[0067] 3.1 1: Phosphorus oxychloride (0.585g, 3.81mmol) was slowly added dropwise to a round-bottomed flask containing DMF (1g, 13.72mmol) in an ice-salt bath, and the ice bath was removed after the addition was completed. Under nitrogen protection, continue stirring at room temperature for half an hour to prepare Vilsmeier-Haack reagent. Then a DMF solution in which julolidine (0.6 g, 3.46 mmol) was dissolved was slowly added dropwise thereto, and after the dropwise addition was completed, it was refluxed at 90° C. for 4 h. The reacted substance was poured into ice water to stop the reaction, and the stirring was continued for at least 2 h, a yellow solid was precipitated, and finally a light yellow solid 1 was obtained by suction filtration.

[0068]3.2 10: Add methoxyacetophenone (375.5mg, 2.5mmol), compound 1 (300mg, 1.476mmol), ethanol (3...

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