Transition metal complexes with (pyridyl)imidazole ligands and sensors using said complexes

• US 6,676,816 B2
• Filed: 05/09/2002
• Issued: 01/13/2004
• Est. Priority Date: 05/11/2001
• 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:
  US10/143,300
• Publication Number:
  US 20030096997A1
• Time in Patent Office: 614 Days
• Field of Search: 204/403.1, 204/403.04, 204/403.14, 204/418, 526/161, 546/2, 548/101
• US Class Current: 204/403.14
• CPC Class Codes: C07F 15/0026 without a metal-carbon linkage

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. The transition metal complexes include substituted or unsubstituted(pyridyl)imidazole ligands. Transition metal complexes attached to polymeric backbones are also described.

Claims

1. A transition metal complex having the formula:

wherein c is a negative, neutral, or positive charge represented by −

1 to −

5, 0, or +1 to +5, inclusive, respectively;

M is cobalt, iron, osmium, ruthenium, or vanadium;

L₁ is a substituted or an unsubstituted heterocyclic nitrogen-containing ligand;

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;

R_a and R_b 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;

R′

₃, R′

₄ 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, or a combination of R′

₃ and R′

₄ forms a saturated or unsaturated 5- or 6-membered ring; and

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, or a combination of Rc and Rd forms a saturated or unsaturated 5- or 6-membered ring.

2. The complex of claim 1, wherein R′

₁ is a substituted or an unsubstituted C1-C12 alkyl or alkenyl.

3. The complex of claim 1, wherein R′

₁ is methyl.

4. The complex of claim 1, wherein R′

₁ is a substituted or an unsubstituted aryl.

5. The complex of claim 1, wherein R′

₁ is a substituted or an unsubstituted phenyl.

6. The complex of claim 1, wherein R′

₁ is a phenyl substituted with a substituent selected from a group consisting of —

Cl, —

F, —

CN, amino, carboxy, C1-C6 alkyl, C1-C6 alkylthio, C1-C6 alkylamino, C1-C6 dialkylamino, C1-C6 alkylaminocarbonyl, C1-C6 alkoxy, C1-C6 alkoxycarbonyl, and C1-C6 alkylcarboxamido.

7. The complex of claim 1, wherein R′

₃, R′

₄, R_a, R_b, R_c, and R_d are independently —

H or substituted or unsubstituted alkyl.

8. The complex of claim 1, wherein c is 0, +1 or +2.

9. The complex of claim 1, having the formula:

wherein d is a number of counter ions, X, from 1 to 5, inclusive, M is osmium and L₁ is a substituted or an unsubstituted imidazole.

10. The complex of claim 9, wherein d is 2.

11. The complex of claim 9, wherein X is an anion selected from a group consisting of halides, sulfates, phosphates, hexafluorophosphates and tetrafluoroborates.

12. The complex of claim 9, wherein X is chloride.

13. The complex of claim 9, wherein L₂ is chloride.

14. The complex of claim 1, wherein L₁ is a substituted or an unsubstituted imidazole.

15. The complex of claim 1, wherein L₁ is a substituted or an unsubstituted triazole, oxazole, thiazole, or pyrazole.

16. The complex of claim 1, wherein L₁ has the formula:

wherein R₇ is a substituted or an unsubstituted alkyl, alkenyl, or aryl;

R₈ is —

H, —

F, —

Cl, —

Br, —

I, —

NO₂, —

CN, —

CO₂H, —

SO₃H, —

NHNH₂, —

SH, —

OH, —

NH₂, alkoxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkoxy, alkylamino, dialkylamino, alkanoylamino, arylcarboxamido, hydrazino, alkylhydrazino, hydroxylamino, alkoxyamino, alkylthio, alkenyl, aryl, or alkyl; and

R₉ and R₁₀ are independently —

H, —

F, —

Cl, —

Br, —

I, —

NO₂, —

CN, —

CO₂H, —

SO₃H, —

NHNH₂, —

SH, —

OH, —

NH₂, alkoxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkoxy, alkylamino, dialkylamino, alkanoylamino, arylcarboxamido, hydrazino, alkylhydrazino, hydroxylamino, alkoxyamino, alkylthio, alkenyl, aryl, or alkyl, or a combination of R₉ and R₁₀ forms a fused, saturated or unsaturated, 5- or 6-membered ring.

17. The complex of claim 16, wherein R₇ is a substituted or an unsubstituted C1-C12 alkyl or alkenyl.

18. The complex of claim 16, wherein R₉ and R₁₀ form a fused, unsaturated 6-membered ring.

19. The complex of claim 16, wherein R₈, R₉ and R₁₀ are independently —

H or substituted or unsubstituted alkyl.

20. The complex of claim 1, wherein L₁ has the formula:

wherein R₁₁, R₁₂, R₁₃, R₁₄ and R₁₅ are independently —

H, —

F, —

Cl, —

Br, —

I, —

NO₂, —

CN, —

CO₂H, —

OH, —

NH₂, alkoxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkoxy, alkylamino, dialkylamino, alkanoylamino, arylcarboxamido, hydrazino, alkylhydrazino, hydroxylamino, alkoxyamino, alkylthio, alkenyl, aryl, or alkyl.

21. The complex of claim 20, wherein at least one of R₁₁, R₁₂, R₁₃, R₁₄ and R₁₅ is an alkyl substituted with —

F, —

Cl, —

Br, —

I, alkylamino, dialkylamino, trialkylammonium, alkoxy, alkylthio, aryl, or a reactive group, or an aryl substituted with —

F, —

Cl, —

Br, —

I, alkylamino, dialkylamino, alkoxy, alkylthio, aryl, or a reactive group.

22. The complex of claim 20, wherein R₁₁, R₁₂, R₁₃, R₁₄ and R₁₅ are independently —

H, methyl, C1-C2 alkoxy, C1-C2 alkylamino, C2-C4 dialkylamino, or a C1-C6 alkyl substituted with a reactive group.

23. The complex of claim 1, wherein L₂ is selected from a group consisting of —

CN, —

SCN, —

OH, halide, alkoxy, alkylthio, and phenoxide.

24. The complex of claim 1 having a redox potential of from about 0 mV to about −

200 mV, inclusive, relative to a Ag/AgCl reference electrode.

25. The complex of claim 1, wherein M is osmium.

26. The complex of claim 1, wherein at least one of L, L′

, L₁ and L₂ is coupled to a polymeric backbone.

27. The complex of claim 26, wherein the polymeric backbone comprises at least one functional group that is a ligand of the complex.

28. The complex of claim 27, wherein the functional group is selected from a group consisting of pyridine and imidazole groups.

29. A transition metal complex having the formula:

wherein c is a negative or positive charge represented by −

1 to −

5 or +1 to +5, inclusive, respectively;

d is a number of counter ions, X, from 1 to 5, inclusive;

X is chloride;

M is cobalt, iron, osmium, ruthenium, or vanadium;

L₁ is a substituted or an unsubstituted imidazole ligand;

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;

R_a and R_b 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;

R′

₃, R′

₄ 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, or a combination of R′

₃ and R′

₄ forms a saturated or an unsaturated 5- or 6-membered ring; and

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, or a combination of Rc and Rd forms a saturated or an unsaturated 5- or 6-membered ring.

30. The complex of claim 29, wherein R′

₁ is a substituted or an unsubstituted C1-C12 alkyl or alkenyl.

31. The complex of claim 29, wherein R′

₁ is methyl.

32. The complex of claim 29, wherein R′

₁ is a substituted or an unsubstituted aryl.

33. The complex of claim 29, wherein R′

₁ is a substituted or an unsubstituted phenyl.

34. The complex of claim 29, wherein R′

₁ is a phenyl substituted with a substituent selected from a group consisting of —

Cl, —

F, —

CN, amino, carboxy, C1-C6 alkyl, C1-C6 alkylthio, C1-C6 alkylamino, C1-C6 dialkylamino, C1-C6 alkylaminocarbonyl, C1-C6 alkoxy, C1-C6 alkoxycarbonyl, and C1-C6 alkylcarboxamido.

35. The complex of claim 29, wherein R′

₃, R′

₄, R_a, R_b, R_c, and R_d are independently —

H or substituted or unsubstituted alkyl.

36. The complex of claim 29, wherein c is +1 or +2.

37. The complex of claim 36, wherein d is 1 or 2.

38. The complex of claim 37, wherein d is 2.

39. The complex of claim 29, wherein L₁ has the formula:

wherein R₇ is a substituted or an unsubstituted alkyl, alkenyl, or aryl;

R₈ is —

H, —

F, —

Cl, —

Br, —

I, —

NO₂, —

CN, —

CO₂H, —

SO₃H, —

NHNH₂, —

SH, —

OH, —

NH₂, alkoxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkoxy, alkylamino, dialkylamino, alkanoylamino, arylcarboxamido, hydrazino, alkylhydrazino, hydroxylamino, alkoxyamino, alkylthio, alkenyl, aryl, or alkyl; and

R₉ and R₁₀ are independently —

H, —

F, —

Cl, —

Br, —

I, —

NO₂, —

CN, —

CO₂H, —

SO₃H, —

NHNH₂, —

SH, —

OH, —

NH₂, alkoxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkoxy, alkylamino, dialkylamino, alkanoylamino, arylcarboxamido, hydrazino, alkylhydrazino, hydroxylamino, alkoxyamino, alkylthio, alkenyl, aryl, or alkyl, or a combination of R₉ and R₁₀ forms a fused, saturated or unsaturated, 5- or 6-membered ring.

40. The complex of claim 39, wherein R₇ is a substituted or an unsubstituted C1-C12 alkyl or alkenyl.

41. The complex of claim 39, wherein R₉ and R₁₀ form a fused, unsaturated 6-membered ring.

42. The complex of claim 39, wherein R₈, R₉ and R₁₀ are independently —

H or substituted or unsubstituted alkyl.

43. The complex of claim 29, wherein L₂ is selected from a group consisting of —

CN, —

SCN, —

OH, halide, alkoxy, alkylthio, and phenoxide.

44. The complex of claim 29, wherein L₂ is chloride.

45. The complex of claim 29, having a redox potential of from about 0 mV to about −

200 mV, inclusive, relative to a Ag/AgCl reference electrode.

46. The complex of claim 29, wherein M is osmium.

47. The complex of claim 29, wherein at least one of L, L′

, L₁ and L₂ is coupled to a polymeric backbone.

48. The complex of claim 47, wherein the polymeric backbone comprises at least one functional group that is a ligand of the complex.

49. The complex of claim 48, wherein the functional group is selected from a group consisting of pyridine and imidazole groups.

50. A transition metal complex having the formula:

wherein c is a neutral or positive charge represented by 0, or +1 to +3, inclusive, respectively;

M is osmium;

L₁ is a substituted or an unsubstituted heterocyclic nitrogen-containing ligand;

L₂ is from a group consisting of —

CN, —

SCN, —

OH, halide, alkoxy, alkylthio, and phenoxide; and

L and L′

are independently;

wherein R′

₁ is a substituted or an unsubstituted C1-C12 alkyl; and

R′

₃, R′

₄, R_a, R_b, R_c, and R_d are independently —

H or substituted or unsubstituted alkyl.

51. The complex of claim 50 having the formula:

wherein d is a number of counter anions, X, from 1 to 5, inclusive.

52. The complex of claim 51, wherein X is an anion selected from a group consisting of halides, sulfates, phosphates, hexafluorophosphates and tetrafluoroborates.

53. The complex of claim 50, wherein L₁ is a substituted or an unsubstituted imidazole.

54. The complex of claim 50, wherein L₁ is a substituted or an unsubstituted triazole, oxazole, thiazole, or pyrazole.

55. The complex of claim 50 wherein L₁ has the formula:

wherein R₇ is a substituted or an unsubstituted C1-C12 alkyl or alkenyl; and

R₈, R₉ and R₁₀ are independently —

H or substituted or unsubstituted alkyl.

56. The complex of claim 50, wherein L₁ has the formula:

wherein R₁₁, R₁₂, R₁₃, R₁₄ and R₁₅ are independently —

H, methyl, C1-C2 alkoxy, C1-C2 alkylamino, C2-C4 dialkylamino, or a C1-C6 alkyl substituted with a reactive group.

57. The complex of claim 50, having a redox potential of from about 0 mV to about −

200 mV, inclusive, relative to a Ag/AgCl reference electrode.

58. The complex of claim 50, wherein at least one of L, L′

, L₁ and L₂ is coupled to a polymeric backbone.

59. The complex of claim 58, wherein the polymeric backbone comprises at least one functional group that is a ligand of the complex.

60. The complex of claim 59, wherein the functional group is selected from a group consisting of pyridine and imidazole groups.

61. A sensor comprising:

a working electrode;

a counter electrode;

an enzyme disposed proximate to the working electrode;

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

wherein c is a negative, neutral, or positive charge represented by −

1 to −

5, 0, or +1 to +5, inclusive, respectively;

M is cobalt, iron, osmium, ruthenium, or vanadium;

L₁ is a substituted or an unsubstituted heterocyclic nitrogen-containing ligand;

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;

R_a and R_b 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;

R′

₃, R′

₄ 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, or a combination of R′

₃ and R′

₄ forms a saturated or an unsaturated 5- or 6-membered ring; and

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, or a combination of R_c and R_d forms a saturated or an unsaturated 5- or 6-membered ring.

62. The sensor of claim 61 having the formula:

wherein d is a number of counter ions, X, from 1 to 5, inclusive.

63. The sensor of claim 62, wherein X is an anion selected from a group consisting of halides, sulfates, phosphates, hexafluorophosphates and tetrafluoroborates.

64. The sensor of claim 61, wherein c is a neutral or positive charge represented by 0, or +1 to +3, inclusive, respectively;

M is osmium;

L₂ is selected from a group consisting of —

CN, —

SCN, —

OH, halide, alkoxy, alkylthio, and phenoxide;

L′

₁ is a substituted or an unsubstituted C1-C12 alkyl; and

R′

₃, R′

₄, R_a, R_b, R_c, and R_d are independently —

H or substituted or unsubstituted alkyl groups.

65. The sensor of claim 61, wherein the redox mediator has a redox potential of from about 0 mV to about −

200 mV, inclusive, relative to a Ag/AgCl reference electrode.

66. The sensor of claim 61, wherein the redox mediator is coupled to a polymeric backbone via at least one of L, L′

, L₁ and L₂.

67. The sensor of claim 66, wherein the polymeric backbone comprises at least one functional group that is a ligand of the complex.

68. The sensor of claim 67, wherein the functional group is selected from a group consisting of pyridine and imidazole groups.

69. The sensor of claim 61, wherein the redox mediator is crosslinked on the working electrode.

70. The sensor of claim 61, wherein the redox mediator and the enzyme are crosslinked on the working electrode.