Fluorogenic or fluorophoric compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-9434975-B2
Application number	US-201214008905-A
Country	US
Kind code	B2
Filing date	Mar 5, 2012
Priority date	Mar 30, 2011
Publication date	Sep 6, 2016
Grant date	Sep 6, 2016

Abstract

Compounds are provided that are either fluorogenic or fluorophoric. Compositions and articles that include the compounds are also provided. Additionally, methods of detecting a microorganism using the compounds are provided. The compounds are fluorinated and can be used advantageously under acidic conditions.

First claim

What is claimed is:

1. A compound of Formula (I)

wherein
R 1 is —(CO)—OR 3 , —(CO)—NR 4 R 5 , heterocyclic group, aryl, aralkyl, or cyano;
R 2 is an enzyme-labile group;
R 3 is alkyl, alkenyl, aryl, or aralkyl;
R 4 and R 5 are each independently hydrogen, alkyl, aryl, or aralkyl; and
either (a) X 1 is hydrogen and X 2 is fluoro or (b) X 1 is fluoro and X 2 is hydrogen, and wherein R 2 is a sugar group, sugar acid group, amino sugar group, carboxyl-terminated amino acid group, carboxyl-terminated peptide group, ester group, ester-containing group, phosphate group, or sulfate group; and wherein either
R 2 is a sugar group that is a monosaccaride group or a disaccharide group, or
R 1 is —(CO)—OR 3 where R 3 is alkyl, or
R 2 is a sugar group that is a monosaccaride group or a disaccharide group and R 1 is —(CO)—OR 3 where R 3 is alkyl.

2. The compound of claim 1 , wherein R 2 is a sugar group that is a monosaccharide group or disaccharide group.

3. The compound of claim 1 , wherein R 1 is —(CO)—OR 3 where R 3 is an alkyl.

4. The compound of claim 1 , wherein R 1 is a heterocyclic group having a five-member heterocyclic ring.

5. The compound of claim 1 , wherein R 1 is a heterocyclic group having a five-member heterocyclic ring fused to a benzene ring.

6. A composition comprising a mixture of a compound of Formula (I-1) and a compound of Formula (I-2);

wherein
R 1 is —(CO)—OR 3 , —(CO)—NR 4 R 5 , heterocyclic group, aryl, aralkyl, or cyano;
R 2 is hydroxyl or an enzyme-labile group;
R 3 is alkyl, alkenyl, aryl, or aralkyl; and
R 4 and R 5 are each independently hydrogen, alkyl, aryl, or aralkyl.

7. An article comprising:
a) a first layer that is a support layer;
b) a second layer adjacent to the support layer, wherein the second layer comprises a compound of Formula (I) according to claim 1 .

8. The article of claim 7 , wherein the second layer comprises a mixture of a compound of Formula (I-1) and a compound of Formula (I-2)

wherein
R 1 is —(CO)—OR 3 , —(CO)—NR 4 R 5 , heterocyclic group, aryl, aralkyl, or cyano;
R 2 is hydroxyl or an enzyme-labile group;
R 3 is alkyl, alkenyl, aryl, or aralkyl; and
R 4 and R 5 are each independently hydrogen, alkyl, aryl, or aralkyl.

9. The article of claim 7 , wherein the second layer further comprises a gelling agent, growth medium, or a combination thereof.

10. The article of claim 7 , wherein the second layer is dehydrated.

11. The article claim 7 , wherein the second layer further comprises polymeric particles.

12. The article of claim 11 , wherein the polymeric particles comprise an acrylate polymer or copolymer, styrene polymer or copolymer, cellulosic polymer or copolymer, dextran polymer or copolymer, derivatives thereof, or combinations thereof.

13. The article of claim 11 , wherein the polymeric particles have an average particle diameter in a range of 0.01 micrometers to 1 micrometer.

14. A method of detecting a microorganism, the method comprising:
providing a compound of Formula (I) according to claim 1 ; and
incubating a test sample with the compound of Formula (I), wherein the test sample contains an enzyme that cleaves the R 2 group of compound of Formula (I), resulting in the formation of a fluorophoric compound of Formula (Ib); and

exciting the fluorophoric compound of Formula (Ib) with a first wavelength of light and detecting light emitted at a second wavelength of light that is longer than first wavelength of light.

15. The method of claim 14 , wherein the step of incubating the test sample with the fluorogenic compound comprises adding the test sample in a liquid form to a dehydrated layer containing the fluorogenic compound of Formula (Ia) and a growth medium.

16. The method of claim 14 , wherein the method further comprises sequestering the compound of Formula (Ib) on polymeric particles.

17. The method of claim 16 , wherein the polymeric particles have an average particle diameter in a range of 0.01 micrometers to 1 micrometer.

Assignees

• Roscoe Stephen B
• Chou Shih-Hung
• Moeller Stephanie J
• Miller Jesse D
• Halverson Kurt J
• Bjork Jason W
• 3M Innovative Properties Co

Inventors

• Roscoe Stephen B
• Chou Shih-Hung
• Moeller Stephanie J
• Miller Jesse D
• Halverson Kurt J
• Bjork Jason W

Classifications

• C07D311/16 Primary

  substituted in position 7 · CPC title

• C07D405/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D409/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C12Q1/04 Primary

  Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor {(C12Q1/6897 takes precedence)} · CPC title

• C07H17/075

  Benzo[b]pyran-2-ones · CPC title