# US 2021/0333263 A1 · Redox activatable fluorescent sensors

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- Number: US 2021/0333263 A1
- Document ID: US20210333263A1
- Status: Published application
- Kind: A1
- Application number: 16/333,164
- Filed: 2017-09-12
- Published: 2021-10-28
- Earliest claimed: 2016-09-16
- Applicants: The Board of Regents of the University of Texas System
- Inventors: Jinming GAO; Zhaohui WANG; Min LUO; Qi WEI; Gang HUANG
- Web page: https://patentgrep.com/patent/US20210333263A1

## CPC

- C12Q 1/00: Measuring or testing processes involving enzymes, nucleic acids or microorganisms (measuring or testing apparatus with condition measuring or sensing means, e.g. colony counters, C12M1/34); Compositions therefor; Processes of preparing such compositions
- G01N 33/502: {for testing non-proliferative effects}
- C09K 11/07: having chemically-interreactive components, e.g. reactive chemiluminescent compositions
- G01N 21/6428: {Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" (in vivo A61B5/00; immunoassay G01N33/53)}
- G01N 33/542: with steric inhibition or signal modification, e.g. fluorescent quenching
- G01N 2021/6432: {Quenching}
- G01N 2021/6439: {with indicators, stains, dyes, tags, labels, marks}
- G01N 2500/10: involving cells
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- C09K: MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE

## Abstract

Provided herein are compounds of the formula: (I) wherein the variables are defined herein, which may be used as redox-activatable sensors. In some aspects, the compounds are fluorescence sensors which are activated by the redox state of the cell. Also provided herein are methods of using these compounds to image the cellular environment or the delivery of macromolecules to a cell.

## Claims

### Claim 1

A compound of the formula:
wherein:
R1 is a first label, amino, hydroxy, alkoxy(C≤8), substituted alkoxy(C≤8), alkylamino(C≤8), substituted alkylamino(C≤8), dialkylamino(C≤8), substituted dialkylamino(C≤8), an amine reactive group; a thiol reactive group, an organic polymer, a nucleic acid sequence, a peptide, or a protein;
R2 is a first label, hydrogen, alkyl(C≤8), substituted alkyl(C≤8), an organic polymer, a nucleic acid sequence, a peptide, or a protein;
R3 is a second label; and
m and n are each independently 0, 1, 2, or 3;
provided that either R1 or R2 is a first label.

### Claim 2 (depends on 1)

The compound of claim 1 further defined as:
wherein m, R1, R2, and R3 are as defined above.

### Claim 3 (depends on 2)

The compound of claim 2 further defined as:
wherein R1, R2, and R3 are as defined above.

### Claim 4 (depends on 1)

The compound according to claim 1, wherein R2 or R3 is a fluorescent dye.

### Claim 5 (depends on 4)

The compound of claim 4, wherein R2 or R3 are fluorescent dyes.

### Claim at position 6

6-9. (canceled)

### Claim 10 (depends on 4)

The compound of claim 4, wherein R2 or R3 is a xanthene dye.

### Claim 11

(canceled)

### Claim 12 (depends on 4)

The compound of claim 4, wherein R2 or R3 is a cyanine dye, a coumarin dye or a BODIPY dye.

### Claim at position 10

13-14. (canceled)

### Claim 15 (depends on 1)

The compound according to claim 1, wherein R2 or R3 is a fluorescent quencher.

### Claim at position 12

16-17. (canceled)

### Claim 18 (depends on 1)

The compound according to claim 1, wherein m is 1 or 2.

### Claim 19 (depends on 1)

The compound according to claim 1, wherein n is 0 or 1.

### Claim 20 (depends on 1)

The compound according to claim 1, wherein R1 is hydroxy and thereby forms a carboxylic acid.

### Claim 21 (depends on 1)

The compound according to claim 1, wherein R1 is an amine reactive group.

### Claim 22

(canceled)

### Claim 23 (depends on 1)

The compound according to claim 1, wherein R1 is an organic polymer, a nucleic acid sequence, a peptide, or a protein.

### Claim at position 19

24-27. (canceled)

### Claim 28 (depends on 1)

The compound according to claim 1, wherein the compound is further defined as:
wherein:
R2 and R3 are each independently a fluorescent dye or a fluorescent quencher; and
A is a peptide, protein, or nucleic acid.

### Claim at position 21

29-31. (canceled)

### Claim 32 (depends on 1)

A composition comprising:
(a) a compound according to claim 1; and
(b) a polymer;
wherein the polymer forms a micelle.

### Claim 33 (depends on 32)

The composition of claim 32, wherein the polymer is a compound of the formula:
wherein:
Y1 is hydrogen, alkyl(C≤12), cycloalkyl(C≤12), substituted alkyl(C≤12), substituted cycloalkyl(C≤12), a cell targeting moiety, or a conjugating group;
n is an integer from 1 to 500;
Y2 and Y2′ are each independently selected from hydrogen, alkyl(C≤12), cycloalkyl(C≤12), substituted alkyl(C≤12), or substituted cycloalkyl(C≤12);
Y3 is a group of the formula:
wherein:
nx is 0-3;
X1, X2, and X3 are each independently selected from hydrogen, alkyl(C≤12), cycloalkyl(C≤12), substituted alkyl(C≤12), or substituted cycloalkyl(C≤12); and
X4 and X5 are each independently selected from alkyl(C≤12), cycloalkyl(C≤12), or a substituted version of any of these groups, or X4 and X5 are taken together and are alkanediyl(C≤12), alkoxydiyl(C≤12), alkylaminodiyl(C≤12), or a substituted version of any of these groups;
x is an integer from 1 to 150;
Y4 is a group of the formula:
wherein:
ny is 0-3;
X1′, X2′, and X3′ are each independently selected from hydrogen, alkyl(C≤12), cycloalkyl(C≤12), substituted alkyl(C≤12), or substituted cycloalkyl(C≤12); and
X4′ and XV′ are each independently selected from hydrogen, alkyl(C≤12), cycloalkyl(C≤12), acyl(C≤12), substituted alkyl(C≤12), substituted cycloalkyl(C≤12), substituted acyl(C≤12), a dye, or a quencher;
y is an integer from 0 to 20; and
Y5 is hydrogen, halo, hydroxy, alkyl(C≤12), or substituted alkyl(C≤12).

### Claim 34 (depends on 1)

A method of determining the redox state of a composition comprising:
(a) contacting the composition with a compound or pharmaceutical composition according to claim 1; and
(b) measuring for a signal from the each of the labels of the compound which indicates a reducing environment.

### Claim 35 (depends on 34)

The method of claim 34, wherein the composition is a cell.

### Claim 36 (depends on 34)

The method of claim 34, wherein the composition is a human body.

### Claim 37 (depends on 34)

The method of claim 34, wherein the composition is a composition outside of a living organism.

### Claim 38 (depends on 34)

The method of claim 34, wherein one of the label allows the imaging of the location of the compound in the composition.