Transition metal complexes with bidentate ligand having an imidazole ring and sensor constructed therewith

• US 6,605,201 B1
• Filed: 11/14/2000
• Issued: 08/12/2003
• Est. Priority Date: 11/15/1999
• Status: Expired due to Term

• Current Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Therasense Incorporated (Abbott Laboratories Incorporated)
• Inventors: Heller, Adam, Mao, Fei
• Primary Examiner(s): Nguyen, Nam
• Assistant Examiner(s): Olsen, Kaj K.
• Application Number:
  US09/712,452
• Time in Patent Office: 1,001 Days
• Field of Search: 204/403.04, 204/403.1, 204/403.14, 204/418, 526/161, 546/2, 548/101
• US Class Current: 204/403.14
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1477 non-invasive
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: C07F 15/0026 without a metal-carbon linkage
• CPC Class Codes: C07F 15/0053 without a metal-carbon linkage
• CPC Class Codes: C07F 15/025 without a metal-carbon linkage
• CPC Class Codes: C07F 15/065 without a metal-carbon linkage
• CPC Class Codes: C07F 9/005 Compounds of elements of Group 5 of the Periodic Table without metal-carbon linkages
• CPC Class Codes: C08F 8/42 Introducing metal atoms or metal-containing groups
• CPC Class Codes: C08F 8/44 Preparation of metal salts or ammonium salts
• CPC Class Codes: C09B 57/10 Metal complexes of organic compounds not being dyes in uncomplexed form
• CPC Class Codes: C12Q 1/004 mediator-assisted

Abstract

Novel transition metal complexes of iron, cobalt, ruthenium, osmium, and vanadium are described. The transition metal complexes can be used as redox mediators in enzyme based electrochemical sensors. In such instances, transition metal complexes accept electrons from, or transfer electrons to, enzymes at a high rate and also exchange electrons rapidly with the sensor. The transition metal complexes include at least one substituted or unsubstituted biimidazole ligand and may further include a second substituted or unsubstituted biimidazole ligand or a substituted or unsubstituted bipyridine or pyridylimidazole ligand. Transition metal complexes attached to polymeric backbones are also described.

Claims

1. A transition metal complex having the formula:

wherein M is osmium;

L is selected from the group consisting of;

R₁, R₂, and R′

₁ are independently substituted or unsubstituted alkyl, alkenyl, or aryl groups;

R₃, R₄, R₅, R₆, R′

₃, R′

₄, R_a, R_b, R_c, and R_d are 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;

c is an integer selected from −

1 to −

5 or +1 to +5 indicating a positive or negative charge;

X represents at least one counter ion;

d is an integer from 1 to 5 representing the number of counter ions, X; and

L₁, L₂, L₃ and L₄ are ligands;

wherein L₁ comprises a heterocyclic compound coupled to a polymeric backbone, and wherein L₁ and L₂ in combination form a first bidentate ligand.

2. The transition metal complex of claim 1, wherein both R₁, R₁′

, and R₂ are unsubstituted C1 to C12 alkyl.

3. The transition metal complex of claim 1, wherein R₃, R₄, R₅ and R₆ are —

H.

4. The transition metal complex of claim 1, wherein L₁ comprises a heterocyclic compound containing at least one nitrogen atom.

5. The transition metal complex of claim 1, wherein the first bidentate ligand comprises a 2,2′

-bipyridine having the following formula;

wherein R₁₆, R₁₇, R₁₈, R₁₉, R₂₀, R₂₁, R₂₂ and R₂₃ are independently —

H,—

F, —

Cl, —

Br, —

I, —

CN, —

CO₂H, —

SO₃H. —

NHNH₂, —

SH, —

OH, —

NH_z, or substituted or unsubstituted alkoxylcarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkoxy, alkylamino, dialkylamino, alkanoylamino, arylcarboxamido, hydrazino, alkylhydrazino, hydroxylamino, alkoxylamino, alkylthio, alkenyl, aryl, or alkyl.

6. The transition metal complex of claim 1, wherein L₃ and L₄ in combination form a second bidentate ligand.

7. The transition metal complex of claim 6, wherein at least one of the first and second bidentate ligands is selected from the group consisting of substituted and unsubstituted 2,2′

-bipyridines, 2,2′

-biimidazoles, and 2-(2-pyridyl)imidazoles.

8. The transition metal complex of claim 1, wherein the transition complex has the following formula:

wherein R₃, r₄, R₅, R₆, R₁₆, R₁₇, R₁₉, R₂₀, R₂₂ and R₂₃ are —

H;

R₁ and R₂ are independently substituted or unsubstituted C1 to C12 alkyls; and

R₁₈ and R₂₁ are independent —

H or substituted or unsubstituted C1-C12 alkoxy, C1-12 alkylthio, C1-C12 alkylamino, C2-C24 dialkylamino, or C1-C12 alkyl.

9. The transition metal complex of claim 8, wherein at least one of R₁, R₂, R₁₈ and R₂₁ comprises a reactive group selected from the group consisting of carboxy, activated ester, sulfonyl halide, sulfonate ester, isocyanate, isothiocyanate, epoxide, aziridine, halide, aldehyde, ketone, amine, acrylamide, thiol, acyl azide, acyl halide, hydrazine, hydroxylamine, alkyl halide, imidazole, pyridine, phenol, alkyl sulfonate, halotriazine, imido ester, maleimide, hydrazide, hydroxy, and photo-reactive azido aryl groups.

10. The transition metal complex of claim 8, wherein at least one of R₁, R₂, R₁₈, and R₂₁ is coupled to a polymeric backbone.

11. The transition metal complex of claim 1, wherein the transition complex has the following formula:

wherein R₃, R₄, R₅, R₆, R′

₃, R′

₄, R_a, and R_c are —

H;

R_d is —

H or methyl;

R_b is —

H or substituted or unsubstituted C1-C12 alkoxy, C1-12 alkylthio, C1-C12 alkylamino, C2-C24 dialkylamino, or C1-C12 alkyl; and

R₁, R′

₁ and R₂ are independently substituted or unsubstituted C1 to C12 alkyl.

12. The transition metal complex of claim 11, wherein at least one of R₁, R₂, and R′

₁ comprises a reactive group selected from the group consisting of carboxy, activated ester, sulfonyl halide, sulfonate ester, isocyanate, isothiocyanate, epoxide, aziridine, halide, aldehyde, ketone, amine, acrylamide, thiol, acyl azide, acyl halide, hydrazine, hydroxyamine, alkyl halide, imidazole, pyridine, phenol, alkyl sulfonate, halotriazine, imido ester, maleimide, hydrazide, hydroxy, and photo-reactive azido aryl groups.

13. The transition metal complex of claim 11, wherein at least one of R₁, R₂, and R′

₁ is coupled to a polymeric backbone.

17. The sensor of claim 2 further comprising an enzyme disposed proximate to the working electrode.

14. A polymer comprising:

a polymeric backbone; and

a transition metal complex having the following formula;

wherein M is osmium;

L is a bidentate ligand comprising at least one imidazole ring;

c is all integer selected from −

1 to −

5 or +1 to +5 indicating a positive or negative charge;

X represents at least one counter ion;

d is an integer from 1 to 5 representing the number of counter ions, X; and

L₁, L₂, L₃ and L₄ are ligands,

wherein L₁ comprises a heterocyclic ring and is coupled to the polymeric backbone, and wherein L₁ and L₂ in combination form a bidentate ligand.

15. The polymer of claim 14, wherein the polymer backbone is selected from the group consisting of styrene/maleic anhydride copolymer, methylvinylether/maleic anhydride copolymer, poly(4-vinylbenzylchloride) copolymer, poly(allylamine) copolymer, poly(4-vinylpyridine) copolymer, poly(4-vinylpyridine), poly(N-vinylimidazole), and poly(4-styrene sulfonate).

16. A sensor comprising:

a working electrode;

a counter electrode; and

a redox mediator disposed proximate to the working electrode, the redox mediator having the formula;

wherein M is osmium;

L is a bidentate ligand comprising at least one imidazole ring;

c is an integer selected from −

1 to −

5 or +1 to +5 indicating a positive or negative charge;

X represents at least one counter ion;

d is an integer from 1 to 5 representing the number of counter ions, X; and

L₁, L₂, L₃ and L₄ are ligands, and

wherein L₁ comprises a heterocyclic ring and is coupled to a polymeric backbone, and wherein L₁ and L₂ in combination form a bidentate ligand.

18. The sensor of claim 16, wherein the redox mediator is non-leachably disposed on the working electrode.