TRANSITION METAL COMPLEXES WITH PYRIDYL-IMIDAZOLE LIGANDS

• US 20090095642A1
• Filed: 04/14/2008
• Published: 04/16/2009
• Est. Priority Date: 05/11/2001
• Status: Active Grant

• Current Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories Incorporated)
• Inventors: Tran, Lam N., LaTour, John, Heller, Adam, Mao, Fei, Liu, Zenghe, Ouyang, Tianmei, Chen, Ting, Feldman, Benjamin
• Granted Patent: US 8,226,814 B2
• Time in Patent Office: Days
• US Class Current: 205/777.5
• CPC Class Codes: C07F 1/005 without C-Metal linkages
• CPC Class Codes: C07F 15/0026 without a metal-carbon linkage

Abstract

Enzyme-based electrochemical sensors comprising transition metal complexes of iron, cobalt, ruthenium, osmium, and vanadium are described. The transition metal complexes can be used as redox mediators and include substituted or unsubstituted pyridyl-imidazole ligands. Transition metal complexes attached to polymeric backbones are also described.

Claims

1. A sensor, for use in detecting the concentration of an analyte in a sample, comprising:

(a) a first electrode, the first electrode being a working electrode; and

(b) a second electrode, the second electrode being a reference electrode;

wherein the first electrode comprises a reagent layer deposited thereon, the reagent layer comprising;

(i) a coordination complex comprising osmium; and

(ii) a dehydrogenase;

wherein the coordination complex comprising osmium facilitates an electrochemical connection between the working electrode and electrons generated from a reaction promoted by the enzyme with a target analyte to be detected and quantified, the coordination complex comprising osmium being characterized by transferring a detectable flow of electrons to the working electrode.

2. The sensor of claim 1, wherein the dehydrogenase is a PQQ-dependent dehydrogenase.

3. The sensor of claim 1, wherein the dehydrogenase is a FAD-dependent dehydrogenase.

4. The sensor of claim 1, wherein the dehydrogenase is an NAD-dependent dehydrogenase.

5. The sensor of any one of claims 2-4, wherein the analyte is selected from the group consisting of glucose, ketone bodies, cholesterol and lactate.

6. The sensor of claim 1, wherein the coordination complex comprising osmium accelerates the electro-oxidation of the target analyte in the presence of the enzyme, allowing for the selective assay of the target analyte in the presence of other electrochemically oxidizable species.

7. The sensor of claim 1, wherein the target analyte is glucose.

8. The sensor of claim 1, wherein the coordination complex comprising osmium is substantially non-reactive with reactants other than those involved in the transfer of electrons to the working electrode.

9. The sensor of claim 1, wherein the coordination complex comprising osmium has the following formula:

wherein each of R and R′

may independently be —

H or alkyl, and wherein each can be and each can be .

10. The sensor of claim 1, wherein the coordination complex comprising osmium has the following formula:

wherein each can be and each can be .

11. The sensor of claim 1, wherein the coordination complex comprising osmium has the following formula:

wherein R is —

H or alkyl, and wherein each can be and each can be .

20. The sensor of claim 1, wherein the coordination complex comprising osmium has the following general formula:

wherein c a positive charge represented by +1 to +5;

M is osmium;

L₁ is a substituted or an unsubstituted heterocyclic nitrogen-containing ligand sufficient to spatially or stereochemically shield M;

L₂ is a negatively charged ligand; and

L and L′

are independently;

wherein R′

₁ is a substituted or an unsubstituted alkyl, alkenyl or aryl;

each of R_a and R_b is independently —

H, —

F, —

Cl, —

Br, —

I, —

NO₂, —

CN, —

CO₂H, —

SO₃H, —

NHNH₂, —

SH, —

OH, —

NH₂, or substituted or unsubstituted alkoxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkoxy, alkylamino, dialkylamino, alkanoylamino, arylcarboxamido, hydrazine, alkylhydrazino, hydroxylamino, alkoxylamino, alkylthio, alkenyl, aryl, or alkyl;

each of R_c and R_d is independently —

H, —

F, —

Cl, —

Br, —

I, —

NO₂, —

CN, —

CO₂H, —

SO₃H, —

NHNH₂, —

SH, —

OH, —

NH₂, or substituted or unsubstituted alkoxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkoxy, alkylamino, dialkylamino, alkanoylamino, arylcarboxamido, hydrazino, alkylhydrazino, hydroxyfamino, alkoxylamino, alkylthio, alkenyl, aryl, or alkyl, or a combination of R_c and R_d forms a saturated or an unsaturated 5- or 6-membered ring; and

each of R′

₃ and R′

₄ is independently —

H, —

F, —

Cl, —

Br, —

I, —

NO₂, —

CN, —

CO₂H, —

SO₃H, —

NHNH₂, —

SH, —

OH, —

NH₂, or substituted or unsubstituted alkoxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkoxy, alkylamino, dialkylamino. alkanoylamino, arylcarboxamido, hydrazino, alkylhydrazino, hydroxylamino, alkoxylamino, alkylthio, alkenyl, aryl, or alkyl, or a combination of R′

₃ and R′

₄ forms a saturated or an unsaturated 5- or 6-membered ring, and wherein each can be and each can be .

21. The sensor of claim 20, wherein L₁ and L₂ are the same.

22. The sensor of claim 20 wherein the coordination complex comprising osmium has the following structure:

wherein R═

NHCH₃, N(CH₃)₂, OCH₃, or OH, and may be attached at any position (ortho, meta, para) on the pyridine ring.

12. An electrode coated with a reagent, the reagent comprising:

(a) a coordination complex comprising osmium; and

(b) an enzyme;

co-factor system;

(i) wherein the coordination complex comprising osmium facilitates an electrochemical connection between the working electrode and electrons generated by a reaction promoted by the enzyme with a target analyte to be detected and quantified, the coordination complex comprising osmium being characterized by transferring a detectable flow of electrons to the working electrode; and

(ii) wherein the enzyme;

co-factor system comprises a dehydrogenase.

13. The electrode of claim 12, wherein the dehydrogenase is a PQQ-dependent dehydrogenase.

14. The electrode of claim 12, wherein the dehydrogenase is a FAD-dependent dehydrogenase.

15. The electrode of claim 12, wherein the dehydrogenase is an NAD-dependent dehydrogenase.

16. The electrode of any one of claims 13-15, wherein the analyte is selected from the group consisting of glucose, ketone bodies, cholesterol and lactate.

17. The electrode of claim 12 wherein the coordination complex comprising osmium has the following formula:

wherein R is —

H or alkyl, and wherein each can be and each can be .

18. A method of determining glucose concentration, comprising the steps of:

(a) contacting a body fluid comprising glucose with a sensor comprised of an electrode, a coordination complex comprising osmium and FAD-glucose dehydrogenase;

(b) allowing electrons generated as a result of a reaction catalyzed by FAD-glucose dehydrogenase to flow to the electrode via the transition meal complex to thereby generate an electrical signal proportionally related to the glucose concentration in the body fluid.

19. The method of claim 18 wherein the coordination complex comprising osmium has the following formula:

wherein R is —

H or alkyl, and wherein each can be and each can be .