Diarylether-based fluorogenic probes for detection of hypochlorous acid or hydroxyl radical

Patent metadata

Field	Value
Publication number	US-10684294-B2
Application number	US-201615135788-A
Country	US
Kind code	B2
Filing date	Apr 22, 2016
Priority date	Apr 22, 2015
Publication date	Jun 16, 2020
Grant date	Jun 16, 2020

Abstract

Provided herein are improved fluorogenic compounds and probes that can be used as reagents for measuring, detecting and/or screening hypochlorous acid or hydroxyl radical. The fluorogenic compounds of the invention can produce fluorescence colors, such as green, yellow, red, or far-red. Also provided herein are fluorogenic compounds for selectively staining hypochlorous acid or hydroxyl radical in the mitochondria of living cells. Provided also herein are methods that can be used to measure, directly or indirectly, the presence and/or amount of hypochlorous acid or hydroxyl radical in chemical samples and biological samples such as cells and tissues in living organisms. Also provided are high-throughput screening methods for detecting or screening hypochlorous acid or hydroxyl radical or compounds that can increase or decrease the level of hypochlorous acid or hydroxyl radical in chemical and biological samples.

First claim

We claim:

1. A compound or a tautomer thereof, wherein the compound has one of structures 21-36 or 46-61:

2. A fluorogenic probe composition comprising the compound of claim 1 , and, optionally, a carrier.

3. The fluorogenic probe composition of claim 2 , wherein the fluorogenic probe composition further comprises a solvent, an acid, a base, a buffer solution, or a combination thereof.

4. A method for detecting the presence of, and/or determining the level of superoxide in a sample, comprising:
a) contacting a compound of claim 1 with the sample to form a fluorescent compound; and
b) determining fluorescence property of the fluorescent compound.

5. The method of claim 4 , wherein the sample is a chemical sample or biological sample.

6. The method of claim 5 , wherein the sample is a biological sample comprising a microorganism, or a cell or tissue.

7. A method for detecting the presence of, or determining the level of hypochlorous acid or hydroxyl radical in vivo in an organism, comprising:
a) administering a compound of claim 1 to the organism to form a fluorescent compound; and
b) determining fluorescence property of the fluorescent compound.

8. A high-throughput screening method for detecting the presence of, or determining the level of, hypochlorous acid or hydroxyl radical in samples, wherein the high-throughput method comprises the steps of:
a) contacting a compound of claim 1 with the samples to form one or more fluorescent compounds; and
b) determining fluorescence properties of the fluorescent compounds to determine the presence and/or amount of hypochlorous acid or hydroxyl radical in the samples.

9. A high-throughput method for screening one or more target compounds that increase or decrease the level of hypochlorous acid or hydroxyl radical, wherein the high-throughput method comprises the steps of:
a) contacting a compound of claim 1 with target compounds to form one or more fluorescent compounds; and
b) measuring fluorescence properties of the florescent compounds to determine the presence and/or amount of the target compounds.

Assignees

• Univ Hong Kong

Inventors

• Yang Dan
• Hu Jun
• Wong Nai-Kei
• Bai Xiaoyu

Classifications

• C09B11/08

  Phthaleins; {Phenolphthaleins; Fluorescein} · CPC title

• G01N33/582

  with fluorescent label · CPC title

• C07D493/10

  Spiro-condensed systems · CPC title

• C07D491/20

  Spiro-condensed systems · CPC title

• G01N33/84 Primary

  involving inorganic compounds or pH · CPC title