Polyviologen boronic acid quenchers for use in analyte sensors

1. A polyviologen compound comprising two or more viologen moieties, wherein each viologen moiety includes at least two boronic acid functional groups, and wherein the polyviologen compound comprises a coupling group.

2. The polyviologen compound of claim 1 , wherein the polyviologen is derived from a 3,3′ dipyridyl intermediate.

3. A compound of claim 1 having the following structure:

wherein

Z is either a reactive, ethylenically unsaturated group or a reactive functional group, capable of forming a covalent bond with a polymer or matrix;

Y is a trivalent connecting group selected from

where R is H or a lower alkyl, and

X − is a counterion;

X 1 and X 2 are —O— or —NH—; and

L 1 , L 2 , and L 3 are selected from the group consisting of a direct bond and a lower alkylene having 1 to 8 carbon atoms, optionally terminated with or interrupted by one or more divalent connecting groups selected from the group consisting of sulfonamide (—SO 2 NH—), amide —(C═O)N—, ester —(C═O)—O—, ether —O—, sulfide —S—, sulfone (—SO 2 —), phenylene —C 6 H 4 —, urethane —NH(C═O)—O—, urea —NH(C═O)NH—, thiourea —NH(C═S)—NH—, amide —(C═O)NH— and amine —NR— (where R is defined as alkyl having 1 to 6 carbon atoms) or combinations thereof.

4. The compound of claim 3 wherein Z is a reactive, ethylenically unsaturated group selected from the group consisting of methacrylamido-, acrylamido-, methacryloyl-, acryloyl- and styryl-.

5. The compound of claim 3 wherein Z is a reactive functional group, capable of forming a covalent bond with a polymer or matrix selected from the group consisting of —Br, —OH, —SH, —CO 2 H, and —NH 2 .

6. The compound of claim 3 wherein Z is

wherein R is H or CH 3 .

7. A compound of claim 1 having the following structure:

wherein

X − is a counterion;

L is a divalent linking selected from the group consisting of a direct bond and a lower alkylene having 1 to 8 carbon atoms, optionally terminated with or interrupted by one or more divalent connecting groups selected from the group consisting of sulfonamide (—SO 2 NH—), amide —(C═O)N—, ester —(C═O)—O—, ether —O—, sulfide —S—, sulfone (—SO 2 —), phenylene —C 6 H 4 —, urethane —NH(C═O)—O—, urea —NH(C═O)NH—, thiourea —NH(C═S)—NH—, amide —(C═O)NH— and amine —NR— (where R is defined as alkyl having 1 to 6 carbon atoms) or combinations thereof;

Z is either a reactive, ethylenically unsaturated group or a reactive functional group, capable of forming a covalent bond with a polymer or matrix;

the bond from the central benzene ring is to the ortho, meta or para position on the adjacent pyridinium rings; and

—B(OH) 2 may be in the ortho, meta or para position.

8. The compound of claim 7 wherein Z is a reactive, ethylenically unsaturated group selected from the group consisting of methacrylamido-, acrylamido-, methacryloyl-, acryloyl- and styryl-.

9. The compound of claim 7 wherein Z is a reactive functional group, capable of forming a covalent bond with a polymer or matrix selected from the group consisting of —Br, —OH, —SH, —CO 2 H, and —NH 2 .

10. The compound of claim 7 wherein Z is

wherein R is H or CH 3 .

11. A compound of claim 7 having the following structure:

12. A method of making the compound of claim 11 , comprising the steps of:

13. A compound of claim 1 having the following structure:

wherein:

Z is either a reactive, ethylenically unsaturated group or a reactive functional group, capable of forming a covalent bond with a polymer or matrix;

Y is a trivalent connecting group selected from

where R is H or a lower alkyl, and

X − is a counterion;

X 1 , X 2 , X 3 and X 4 are —O— or —NH—; and

L 1 , L 2 , and L 3 are selected from the group consisting of a direct bond and a lower alkylene having 1 to 8 carbon atoms, optionally terminated with or interrupted by one or more divalent connecting groups selected from the group consisting of sulfonamide (—SO 2 NH—), amide —(C═O)N—, ester —(C═O)—O—, ether —O—, sulfide —S—, sulfone (—SO 2 —), phenylene —C 6 H 4 —, urethane —NH(C═O)—O—, urea —NH(C═O)NH—, thiourea —NH(C═S)—NH—, amide —(C═O)NH— and amine —NR— (where R is defined as alkyl having 1 to 6 carbon atoms) or combinations thereof.

14. The compound of claim 13 wherein Z is a reactive, ethylenically unsaturated group selected from the group consisting of methacrylamido-, acrylamido-, methacryloyl-, acryloyl- and styryl-.

15. The compound of claim 13 wherein Z is a reactive functional group, capable of forming a covalent bond with a polymer or matrix selected from the group consisting of —Br, —OH, —SH, —CO 2 H, and —NH 2 .

16. The compound of claim 13 wherein Z is

wherein R is H or CH 3 .

17. A compound of claim 13 having the following structure:

18. A method of making the compound of claim 17 , comprising the steps of:

19. The compound:

wherein n is equal to 1, 2, 3, or 4.

20. A method of making the compound of claim 19 , comprising the steps of:

wherein n is equal to 1, 2, 3, or 4.

21. A method of making the compound of claim 19 comprising the steps of:

wherein n is equal to 4.

22. An analyte sensor, comprising any one or more of the compounds of claims 1 - 19 , 7 - 11 and 13 - 17 and a fluorescent dye.

23. The analyte sensor of claim 22 , wherein said any one or more of the compounds are in the form of a polymer.

24. The analyte sensor of claim 22 , wherein the analyte is glucose.

25. The analyte sensor of claim 24 , further comprising a glucose permeable immobilizing means.

26. The analyte sensor of claim 24 , wherein said glucose permeable immobilizing means is a polymer matrix or a semipermeable membrane.

27. A composition of matter, comprising a fluorophore that is susceptible to quenching by a viologen, a polyviologen derived from a 3,3′ dipyridyl intermediate comprising two or more viologen moieties, wherein each viologen moiety includes at least two boronic acid functional groups, and a glucose permeable polymer matrix.

28. The composition of claim 27 , wherein the fluorophore has at least one negative charge.