Fast response novel NO (nitrogen oxide) probe as well as preparation method and application thereof

Abstract

The invention relates to a fast response novel NO (nitrogen oxide) probe as well as a preparation method and application thereof, and belongs to the technical field of an organic fluorescent probe. The participation mechanism of NO in different physiological processes is not sufficiently disclosed; in addition, the donor release is uncontrollable; the release dynamics in cells and living bodies are complicated. Therefore the development of a fast response NO probe is necessary. The designed XNO series probe has the maximum characteristics that the reaction speed is high; after the reaction, the fluorescence is greatly increased. The probe has the characteristics of relatively good chemical stability, bio-compatibility, selectivity and the like. Laser co-focusing imaging experiments show that the probe has good cellular permeability; no toxic and side effects are caused on cells and living bodies; the cell level NO content detection can be realized; the probe has important significancewhen being further applied to the early stage detection study of parkinsonism. The formula (I) is shown in the description.

Description

technical field

[0001] The invention relates to a fast-response novel nitric oxide probe, a preparation method and application thereof, and belongs to the technical field of organic fluorescent probes. Background technique

[0002] Nitric oxide (Nitric Oxide, NO) is an important endogenous small molecule in the body, which plays an important role in various life activities. The mechanism of NO involvement in different physiological processes has not been fully revealed. Nitric oxide donors are a class of small molecule chemical biology tools that are widely used in such studies. The release of nitric oxide donors is uncontrollable, and the release kinetics in cells and in vivo is complex. Studies in recent years have shown that: in the cardiovascular system, nitric oxide plays an important role in maintaining the constant of vascular tension and regulating blood pressure; nitroglycerin treats angina pectoris because it is converted into NO in the body to dilate blood vesse...

Examples

Embodiment 1

[0042] A kind of naphthol fluorophore based on large Stokes shift, the preparation method of the novel nitric oxide probe XNO of fast response is as follows:

[0043] XH3 Dissolve XH2 (1.27g, 6.31mmol) in DCM under ice bath condition, and TiCl 4 (1.4mL, 13mmol) after stirring for 30min, then CH 3 CHCl 2 (0.61mL, 6.94mmol) was slowly added to the above mixture, stirred at 25°C for 12 hours, then extracted with NH4Cl aqueous solution and DCM, spin-dried, and column chromatography gave a yellow solid XH3 with high purity. 1 H-NMR (300MHz, CDCl 3 ): δ10.87(s, 1H), δ8.62(s, 1H), δ7.89(d, J=9Hz, 1H), δ7.63(d, J=9Hz, 1H), δ7.10( t, J=10.5Hz, 1H), δ6.95(d, J=9Hz, 1H), δ4.01(s, 3H), δ3.13(s, 6H).

[0044] XH00C: Dissolve XH3 (1.08g, 4.71mmol) in DCM solution in ice bath, slowly add BBr 3 (7.1mL, 7.1mmol, in DCM 1.0M), stirred at 25°C for 2 hours, added aqueous sodium bicarbonate solution until there were no bubbles, stirred in ice bath for 30 minutes, then extracted with DCM, spin...

Embodiment 2

[0048] A kind of naphthol fluorophore based on large Stokes shift, the preparation method of the novel nitric oxide probe XNO of fast response is as follows:

[0049] XH3: Dissolve XH2 (2.54g) in DCM under ice bath condition, and TiCl 4 (2.8mL) after stirring for 30min, then CH 3 CHCl 2 (1.22mL) was slowly added to the above mixture, stirred at 25°C for 12 hours, then washed with NH 4 Cl aqueous solution and DCM were extracted and spin-dried, and column chromatography gave a yellow solid XH3 with high purity.

[0050] XH00C: Dissolve XH3 (2.16g) in DCM in ice bath, slowly add BBr 3 (14.2mL, in DCM1.0M), stirred at 25°C for 2 hours, added aqueous sodium bicarbonate solution until there were no bubbles, stirred in ice bath for 30 minutes, then extracted with DCM, spin-dried, and obtained yellow solid XH00C by column chromatography

[0051] XNO1: Add naphthol derivative XH00C (200mg), 2-aminophenol (104mg), TsOH (3.54mg) to absolute ethanol (10mL) in turn, reflux at 95°C for ...

Embodiment 3

[0054] A kind of naphthol fluorophore based on large Stokes shift, the preparation method of the novel nitric oxide probe XNO of fast response is as follows:

[0055] XH3: Dissolve XH2 (3.81 g) in DCM under ice-bath conditions, and dissolve TiCl 4 (4.2mL) after stirring for 30min, then CH 3 CHCl 2 (1.83mL) was slowly added to the above mixture, stirred at 25°C for 12 hours, then washed with NH 4 Cl aqueous solution and DCM were extracted and spin-dried, and column chromatography gave a yellow solid XH3 with high purity.

[0056] XH00C: Dissolve XH3 (3.24g) in DCM in ice bath, slowly add BBr 3 (85.2mL, in DCM1.0M), stirred at 25°C for 2 hours, added aqueous sodium bicarbonate solution until there were no bubbles, stirred in ice bath for 30 minutes, then extracted with DCM, spin-dried, and obtained yellow solid XH00C by column chromatography

[0057] XNO1: Add naphthol derivative XH00C (300mg), 2-aminophenol (156mg), TsOH (5.31mg) to absolute ethanol (15mL) in sequence, refl...

technical field

[0001] The invention relates to a fast-response novel nitric oxide probe, a preparation method and application thereof, and belongs to the technical field of organic fluorescent probes. Background technique

[0002] Nitric oxide (Nitric Oxide, NO) is an important endogenous small molecule in the body, which plays an important role in various life activities. The mechanism of NO involvement in different physiological processes has not been fully revealed. Nitric oxide donors are a class of small molecule chemical biology tools that are widely used in such studies. The release of nitric oxide donors is uncontrollable, and the release kinetics in cells and in vivo is complex. Studies in recent years have shown that: in the cardiovascular system, nitric oxide plays an important role in maintaining the constant of vascular tension and regulating blood pressure; nitroglycerin treats angina pectoris because it is converted into NO in the body to dilate blood vesse...

Examples

Embodiment 1

[0042] A kind of naphthol fluorophore based on large Stokes shift, the preparation method of the novel nitric oxide probe XNO of fast response is as follows:

[0043] XH3 Dissolve XH2 (1.27g, 6.31mmol) in DCM under ice bath condition, and TiCl 4 (1.4mL, 13mmol) after stirring for 30min, then CH 3 CHCl 2 (0.61mL, 6.94mmol) was slowly added to the above mixture, stirred at 25°C for 12 hours, then extracted with NH4Cl aqueous solution and DCM, spin-dried, and column chromatography gave a yellow solid XH3 with high purity. 1 H-NMR (300MHz, CDCl 3 ): δ10.87(s, 1H), δ8.62(s, 1H), δ7.89(d, J=9Hz, 1H), δ7.63(d, J=9Hz, 1H), δ7.10( t, J=10.5Hz, 1H), δ6.95(d, J=9Hz, 1H), δ4.01(s, 3H), δ3.13(s, 6H).

[0044] XH00C: Dissolve XH3 (1.08g, 4.71mmol) in DCM solution in ice bath, slowly add BBr 3 (7.1mL, 7.1mmol, in DCM 1.0M), stirred at 25°C for 2 hours, added aqueous sodium bicarbonate solution until there were no bubbles, stirred in ice bath for 30 minutes, then extracted with DCM, spin...

Embodiment 2

[0048] A kind of naphthol fluorophore based on large Stokes shift, the preparation method of the novel nitric oxide probe XNO of fast response is as follows:

[0049] XH3: Dissolve XH2 (2.54g) in DCM under ice bath condition, and TiCl 4 (2.8mL) after stirring for 30min, then CH 3 CHCl 2 (1.22mL) was slowly added to the above mixture, stirred at 25°C for 12 hours, then washed with NH 4 Cl aqueous solution and DCM were extracted and spin-dried, and column chromatography gave a yellow solid XH3 with high purity.

[0050] XH00C: Dissolve XH3 (2.16g) in DCM in ice bath, slowly add BBr 3 (14.2mL, in DCM1.0M), stirred at 25°C for 2 hours, added aqueous sodium bicarbonate solution until there were no bubbles, stirred in ice bath for 30 minutes, then extracted with DCM, spin-dried, and obtained yellow solid XH00C by column chromatography

[0051] XNO1: Add naphthol derivative XH00C (200mg), 2-aminophenol (104mg), TsOH (3.54mg) to absolute ethanol (10mL) in turn, reflux at 95°C for ...

Embodiment 3

[0054] A kind of naphthol fluorophore based on large Stokes shift, the preparation method of the novel nitric oxide probe XNO of fast response is as follows:

[0055] XH3: Dissolve XH2 (3.81 g) in DCM under ice-bath conditions, and dissolve TiCl 4 (4.2mL) after stirring for 30min, then CH 3 CHCl 2 (1.83mL) was slowly added to the above mixture, stirred at 25°C for 12 hours, then washed with NH 4 Cl aqueous solution and DCM were extracted and spin-dried, and column chromatography gave a yellow solid XH3 with high purity.

[0056] XH00C: Dissolve XH3 (3.24g) in DCM in ice bath, slowly add BBr 3 (85.2mL, in DCM1.0M), stirred at 25°C for 2 hours, added aqueous sodium bicarbonate solution until there were no bubbles, stirred in ice bath for 30 minutes, then extracted with DCM, spin-dried, and obtained yellow solid XH00C by column chromatography

[0057] XNO1: Add naphthol derivative XH00C (300mg), 2-aminophenol (156mg), TsOH (5.31mg) to absolute ethanol (15mL) in sequence, refl...

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