Ion selective fluorogenic reagents

• US 5,136,033 A
• Filed: 08/24/1987
• Issued: 08/04/1992
• Est. Priority Date: 08/24/1987
• Status: Expired due to Fees

• Current Assignee: Alliedsignal Inc. (Honeywell International Inc.)
• Original Assignee: Alliedsignal Inc. (Honeywell International Inc.)
• Inventors: Masilamani, Divakaran, Lucas, Mariann E., Hammond, George S.
• Primary Examiner(s): Ivy, C. Warren
• Assistant Examiner(s): Chang, Celia
• Application Number:
  US07/088,370
• Time in Patent Office: 1,807 Days
• Field of Search: 436/73, 436/74, 436/79, 436/172, 436/805, 436/74, 422/50, 422/55, 422/56, 540/450, 540/460, 540/467, 540/468, 540/469, 549/200, 549/348, 549/349, 549/350, 549/351, 549/352
• US Class Current: 540/468
• CPC Class Codes: C07D 273/00 Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00
• CPC Class Codes: C07D 493/04 Ortho-condensed systems
• CPC Class Codes: G01N 33/84 involving inorganic compounds or pH

Abstract

Novel fluorogenic ionophores have been synthesized which selectively bind ions such as potassium and sodium, even in neutral aqueous and alcoholic media and respond to such binding by fluorescence quenching or enhancement. These ionophores are ideal for the selective and direct determination of ions in biological or environmental samples and the like. The ionophores are also suitable for incorporation into fiber optic-based sensors for the continuous in vivo or in vitro monitoring of metal ions in blood or other biological fluids.

Claims

1. An ionophore compound of an ion-recognizing system fused to a signal moiety through two heteroatoms having a non-bonded electron pair, having the formula:

##STR15## wherein said signal moiety is selected from the group consisting of unsubstituted and substituted coumarins, and wherein said ion-recognizing system is a crown ether wherein X₁, and X₂ of said crown ether are the same or different and are selected from the group consisting of S, P, N, O, and Se, Y₁ and Y₂ are the same or different and are selected from the group consisting of O, N, S, and C; and

wherein the repeating unit m is 0 to 12.

2. The ionophore of claim 1 wherein X₁ and X₂ are the same or different and are selected from the group consisting of S, O and N.

3. The ionophore compound of claim 1 wherein X₁ and X₂ are the same and are O or N.

4. The ionophore compound of claim 3 wherein m is 0 to 3.

5. The ionophore compound of claim 4 wherein m is 0 or 1.

6. The ionophore compound of claim 1 wherein the ionophore compound corresponds to a formula selected from the group consisting of:

##STR16## wherein R₁, R₂, R₃ and R₄ are the same or different and are H, hydroxyl, amino, alkyl, aromatic hydrocarbyl, fluoroalkyl, alkylcarbonyloxyl, carboxyl, alkoxyl, mercapto or alkylthio and CE represents a crown ether.

8. The compound of claim 6 wherein R₁, R₂, R₃ and R₄ are the same or different and are selected from H and alkyl having 1 to 4 carbons.

9. The compound of claim 6 wherein R₁, R₂, R₃ and R₄ are the same or different and are selected from H or methyl or ethyl.

14. The ionophore of claim 1 wherein said ionophore is capable of selectively recognizing a Na, K or Li ion.

7. A compound having the following formula:

##STR17## wherein CE is a crown ether.

10. A compound according to claim 7 having the formula:

##STR18## wherein said compound is a fluorogenic reagent selective for the detection of potassium ion.

11. A compound according to claim 7 having the formula:

##STR19## wherein said compound is a fluorogenic reagent selective for the detection of potassium ion.

12. A compound according to claim 7 having the formula:

##STR20## wherein said compound is a fluorogenic reagent for the detection of sodium ion.

13. An ionophore compound comprising an ion-recognizing system fused to a signal moiety through two heteroatoms having a non-bonded electron pair, having the formula:

##STR21## wherein said signal moiety is selected from the group consisting of unsubstituted and substituted coumarins, and wherein said ion-recognizing system is a crown ether, wherein X₁, and X₂ of said crown ether are the same or different and are selected from the group consisting of S, P, N, O, and Se, Y₁ and Y₂ are the same or different and are selected from the group consisting of O, N, S, and C; and

wherein the repeating unit m is 0 to 12; and

wherein r ranges from 0-15 and Q is a quenching group selected from aceto, propionyl, bromoaceto, chloroaceto, benzoyl, dinitrobenzoyl, methylcarbonyl, phenylcarbonyl and cyclohexylcarbonyl.