Transition metal complexes with bidentate ligand having an imidazole ring

• US 7,090,756 B2
• Filed: 08/11/2003
• Issued: 08/15/2006
• 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): Olsen, Kaj K.
• Application Number:
  US10/639,181
• Publication Number:
  US 20040040840A1
• Time in Patent Office: 1,100 Days
• Field of Search: 204/403.1, 204/403.04, 204/403.14, 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 sensor comprising:

a working electrode;

a counter electrode; and

a redox mediator disposed proximate to the working electrode, the redox mediator comprising a polymeric transition metal complex that comprises;

a polymeric backbone;

spacers, each spacer covalently coupled to and extending from the polymeric backbone, each spacer comprising at least one non-cyclic functional group selected from the group consisting of —

(CR^rR^s)—

, —

O—

, —

S—

, —

C(O)O—

, —

S(O)₂NR^k—

, —

OC(O)NR^m—

, —

OC(S)NRⁿ, —

C(O)NR^t—

, —

NR^u—

, —

CR^v═

N—

O—

, —

CR^w═

NNR^x—

, and —

(SiR^yR^z)—

, wherein R^r and R^s are independently hydrogen, chlorine, fluorine, or substituted or unsubstituted alkyl, alkoxy, alkenyl, or alkynyl, and R^k, R^m, Rⁿ, R^t, R^u, R^v, R^w, R^x, R^y, and R^z are independently hydrogen or substituted or unsubstituted alkyl; and

transition metal complexes, each transition metal complex having the formula;

2. The sensor of claim 1, wherein M is osmium.

3. The sensor of claim 1, wherein each heterocycle comprises a nitrogen-containing heterocycle that is coordinatively bound to M via a nitrogen atom of the heterocycle.

4. The sensor of claim 3, wherein the nitrogen-containing heterocycle comprises a substituted or unsubstituted pyridine, a substituted or unsubstituted imidazole, a substituted or unsubstituted 2,2′

-bipyridine, a substituted or unsubstituted 2-(2-pyridyl)imidazole, or a substituted or unsubstituted 2,2′

-biimidazole.

5. The sensor of claim 1, wherein at least two ligands of the L¹, L², L³, L⁴, L⁵, and L⁶ ligands are combined to form at least one multidentate ligand.

6. The sensor of claim 1, wherein at least four ligands of the L¹, L², L³, L⁴, L⁵, and L⁶ ligands are combined to form at least two multidentate ligands.

7. The sensor of claim 6, wherein the each of the at least two multidentate ligands is independently selected from substituted or unsubstituted 2,2′

-bipyridine, substituted or unsubstituted 2-(2-pyridyl)imidazole, or substituted or unsubstituted 2,2′

-biimidazole.

8. The sensor of claim 7, wherein each of the at least two multidentate ligands is independently selected from substituted or unsubstituted 2-(2-pyridyl)imidazole, or substituted or unsubstituted 2,2′

-biimidazole.

9. A polymeric transition metal complex, comprising:

a polymeric backbone;

spacers, each spacer covalently coupled to and extending from the polymeric backbone, each spacer comprising at least one non-cyclic functional group selected from the group consisting of —

(CR^rR^s)—

, —

O—

, —

S—

, —

C(O)O—

, —

S(O)₂NR^k—

, —

OC(O)NR^m, —

OC(S)NRⁿ, —

C(O)NR^t—

, —

NR^u—

, —

CR^v═

N—

O—

, —

CR^w═

NNR^x—

, and —

(SiR^yR^z)—

, wherein R^r and R^s are independently hydrogen, chlorine, fluorine, or substituted or unsubstituted alkyl, alkoxy, alkenyl, or alkynyl, and R^k, R^m, Rⁿ, R^t, R^u, R^v, R^w, R^x, R^y, and R^z are independently hydrogen or substituted or unsubstituted alkyl; and

transition metal complexes, each transition metal complex having the formula;

10. The complex of claim 9, wherein M is osmium.

11. The complex of claim 9, wherein each heterocycle comprises a nitrogen-containing heterocycle that is coordinatively bound to M via a nitrogen atom of the heterocycle.

12. The complex of claim 9, wherein the nitrogen-containing heterocycle comprises a substituted or unsubstituted pyridine, a substituted or unsubstituted imidazole, a substituted or unsubstituted 2,2′

-bipyridine, a substituted or unsubstituted 2-(2-pyridyl)imidazole, or a substituted or unsubstituted 2,2′

-biimidazole.

13. The complex of claim 9, wherein at least four ligands of the L¹, L², L³, L⁴, L⁵, and L⁶ ligands are combined to form at least two multidentate ligands, wherein said at least two multidentate ligands comprises said at least one multidentate ligand.

14. The complex of claim 13, wherein each of the at least two multidentate ligands is independently selected from substituted or unsubstituted 2-(2-pyridyl)imidazole, or substituted or unsubstituted 2,2′

-biimidazole.

15. The complex of claim 13, wherein at least one multidentate ligand of the at least two multidentate ligands is independently selected from substituted or unsubstituted 2,2′

-bipyridine, substituted or unsubstituted 2-(2-pyridyl)imidazole, or substituted or unsubstituted 2,2′

-biimidazole.

16. The complex of claim 9, wherein each spacer comprises a flexible chain of at least four atoms.

17. The complex of claim 9, wherein the complex has a weight average molecular weight of at least 5000 daltons.

18. The complex of claim 9, wherein each spacer comprises a heterocycle.

19. The complex of claim 18, wherein for each spacer, at least one non-cyclic functional group of the spacer is disposed between the heterocycle of the spacer and the complex.

20. The complex of claim 9, wherein the complex has a redox potential negative of +150 mV relative to an SCE reference electrode.

21. A polymeric transition metal complex, comprising:

a polymeric backbone;

spacers, each spacer covalently coupled to and extending from the polymeric backbone, each spacer comprising at least one non-cyclic functional group selected from the group consisting of —

(CR^rR^s)—

, —

O—

, —

S—

, —

C(O)O—

, —

S(O)₂NR^k—

, —

OC(O)NR^m, —

OC(S)NRⁿ, —

C(O)NR^t—

, —

NR^u—

, —

CR^v═

N—

O—

, —

CR^w═

NNR^x—

, and —

(SiR^yR^z)—

, wherein R^r and R^s are independently hydrogen, chlorine, fluorine, or substituted or unsubstituted alkyl, alkoxy, alkenyl, or alkynyl, and R^k, R^m, Rⁿ, R^t, R^u, R^v, R^w, R^x, R^y, and R^z are independently hydrogen or substituted or unsubstituted alkyl, and at least one spacer comprising a heterocycle; and

transition metal complexes, each transition metal complex having the formula;

22. The complex of claim 21, wherein M is osmium.

23. The complex of claim 21, wherein each heterocycle comprises a nitrogen-containing heterocycle that is coordinatively bound to M via a nitrogen atom of the heterocycle.

24. The complex of claim 21, wherein the nitrogen-containing heterocycle comprises a substituted or unsubstituted pyridine, a substituted or unsubstituted imidazole, a substituted or unsubstituted 2,2′

-bipyridine, a substituted or unsubstituted 2-(2-pyridyl)imidazole, or a substituted or unsubstituted 2,2′

-biimidazole.

25. The complex of claim 21, wherein at least two ligands of the L¹, L², L³, L⁴, L⁵, and L⁶ ligands are combined to form at least one multidentate ligand.

26. The complex of claim 21, wherein at least four ligands of the L¹, L², L³, L⁴, L⁵, and L⁶ ligands are combined to form at least two multidentate ligands.

27. The complex of claim 26, wherein each of the at least two multidentate ligands is independently selected from substituted or unsubstituted 2,2′

-bipyridine, substituted or unsubstituted 2-(2-pyridyl)imidazole, or substituted or unsubstituted 2,2′

-biimidazole.

28. The complex of claim 26, wherein each of the at least two multidentate ligands is independently selected from substituted or unsubstituted 2-(2-pyridyl)imidazole, or substituted or unsubstituted 2,2′

-biimidazole.

29. The complex of claim 21, wherein each spacer comprises a flexible chain of at least four atoms.

30. The complex of claim 21, wherein the complex has a weight average molecular weight of at least 5000 daltons.

31. The complex of claim 21, wherein for each spacer, at least one non-cyclic functional group of the spacer is disposed between the heterocycle of the spacer and the complex.

32. The complex of claim 31, wherein for each spacer, at least one non-cyclic functional group of the spacer is disposed between the heterocycle of the spacer and the complex.

33. The complex of claim 21, wherein the complex has a redox potential negative of +150 mV relative to an SCE reference electrode.