Polymeric transition metal complexes and uses thereof

• US 6,605,200 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:
  US09/712,065
• Time in Patent Office: 1,001 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: 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 polymeric transition metal complexes of iron, cobalt, ruthenium, osmium, and vanadium are described. The polymeric transition metal complexes can be electron transfer 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.

Claims

1. A polymeric transition metal complex, comprising:

a polymeric backbone;

a plurality of 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

a plurality of transition metal complexes, each transition metal complex having the formula;

wherein M is osmium;

L¹ is a ligand comprising a heterocycle and is coordinatively bound to M via a heteroatom of the heterocycle;

L², L³, L⁴, L⁵, and L⁶ are ligands comprising a nitrogen-containing heterocycle, wherein each of L¹, L², L³, L⁴, L⁵, and L⁶ is independently a monodentate ligand or combined with at least one other ligand to form a multidentate ligand; and

wherein at least one of L¹, L², L³, L⁴, L⁵, and L⁶ is covalently coupled to a one of the spacers.

2. The polymeric transition metal complex of claim 1, wherein the heterocycle of L¹ comprises a nitrogen-containing heterocycle and is coordinatively bound to M via a nitrogen atom of the heterocycle.

3. The polymeric transition metal complex of claim 2, wherein the nitrogen-containing heterocycle comprises a substituted or unsubstituted pyridine, imidazole, 2,2′

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

-biimidazole.

4. The polymeric transition metal-complex of claim 1, wherein at least two of L¹, L², L³, L⁴, L⁵, and L⁶ are combined to form at least one multidentate ligand.

5. The polymeric transition metal complex of claim 1, wherein at least four of L¹, L², L³, L⁴, L⁵, and L⁶ are combined to form at least two multidentate ligands.

6. The polymeric transition metal complex of claim 1, wherein at least four of L¹, L², L³, L⁴, L⁵, and L⁶ are combined to form at least two multidentate ligands selected from the group consisting of substituted and unsubstituted 2,2′

-bipyridines, 2-(2-pyridyl)imidazoles, and 2,2′

-biimidazoles.

7. The polymeric transition metal complex of claim 6, wherein the transition metal complex comprises at least one substituted or unsubstituted 2,2′

-biimidazole or 2-(2-pyridyl)imidazole.

8. The polymeric transition metal complex of claim 1, wherein the spacer comprises a flexible chain of at least four atoms.

9. The polymeric transition metal complex of claim 1, wherein the polymeric transition metal complex has a weight average molecular weight of at least 5000 daltons.

10. The polymeric transition metal complex of claim 1, wherein each spacer further comprises a heterocycle.

11. The polymeric transition metal complex of claim 10, wherein at least one non-cyclic functional group of the spacer is disposed between the heterocycle of the spacer and the transition metal complex.

12. The polymeric transition metal complex of claim 1, wherein the polymeric transition metal complex has a redox potential negative of +150 mV relative to an SCE reference electrode.

13. The polymeric transition metal complex of claim 1, wherein the transition metal complex has the formula:

wherein M is osmium;

R₁ and R₂ are independently substituted or unsubstituted alkyl;

R₃, R⁴, R₅, and R⁶ are independently —

H, —

F, —

Cl, —

Br, or substituted or unsubstituted C1 to C12 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; and

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

14. The polymeric transition metal complex of claim 1, wherein the transition metal complex has the formula:

wherein M is osmium;

R′

₁ is substituted or unsubstituted alkyl;

R′

₃ and R′

₄ are independently —

H, —

F, —

Cl, —

Br, or substituted or unsubstituted C1 to C12 alkyl;

R_a, R_b, R_c and R_d are independently —

H, —

F, —

Cl, —

Br, —

CN, —

CO₂H, —

SO₃H, —

NO₂, —

NH₂, —

NHNH₂ , —

SH, or substituted or unsubstituted C1 to C12 alkylamino, C2 to C24 dialkylamino, C1 to C12 alkoxy, or C1 to C12 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; and

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

15. The polymeric transition metal complex of claim 1, wherein the transition metal complex has the formula:

wherein M is osmium;

R₁₈ and R₂₁ are independently —

H, —

F, —

Cl, —

Br, —

CN, —

CO₂H, —

OH, —

SO₃H, —

NO₂, —

NH₂, —

NHNH₂ , —

SH, or substituted or unsubstituted C1 to C12 alkylamino, C2 to C24 dialkylamino, C1 to C12 alkoxy, or C1 to C12 alkyl

R₁₆, R₁₇, R₁₉, R₂₀, R₂₂ and R₂₃ are independently —

H, or substituted or unsubstituted C1 to C12 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; and

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

16. A polymeric transition metal complex comprising:

a polymeric backbone;

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

(CR^rR^s)—

, —

O—

, —

S—

, —

S(O)₂NR^k—

, —

OC(O)NR^m—

, —

OC(S)NRⁿ, —

C(O)NR^t—

, and —

NR^u—

, wherein R^k, R^m, Rⁿ, R^r, R^s, R^t, and R^u are independently selected from the group consisting of hydrogen and substituted or unsubstituted alkyl;

a plurality of transition metal complexes, each transition metal complex having the formula;

wherein M is osmium;

L¹ is a ligand comprising a heterocycle and is coordinatively bound to M via a heteroatom of the heterocycle;

L2, L³, L⁴, L⁵, and L⁶ are ligands, wherein each of L¹, L², L³, L⁴, L⁵, and L⁶ independently a monodentate ligand or combined with at least one other ligand to form a multidentate ligand; and

wherein at least one of L¹, L², L³, L⁴, L⁵, and L⁶ is covalently coupled to a one of the spacers.

17. A polymeric transition metal complex, comprising:

a polymeric backbone;

a plurality of spacers, each spacer covalently coupled to and extending from the polymeric backbone, each spacer comprising a flexible chain of at least four atoms;

a plurality of transition metal complexes, each transition metal complex having the formula;

wherein M is osmium;

L¹ is a ligand comprising a heterocycle and is coordinatively bound to M via a heteroatom of the heterocycle;

L², L³, L⁴, L⁵, and L⁶ are ligands comprising a nitrogen-containing heterocycle, wherein each of L¹, L², L³, L⁴, L⁵, and L⁶ is independently a monodentate ligand or combined to form one or more multidentate ligands; and

wherein at least one of L¹, L², L³, L⁴, L⁵, and L⁶ is covalently coupled to a one of the spacers.

18. The polymeric transition metal complex of claim 17, wherein the flexible chain is a flexible chain of at least eight atoms.

19. A redox mediator, comprising:

a polymeric backbone;

a plurality of 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;

a plurality of transition metal complexes, each transition metal complex having the formula;

wherein M is osmium;

L¹ is a ligand comprising a heterocycle and is coordinatively bound to M via a heteroatom of the heterocycle;

L², L³, L⁴, L⁵, and L⁶ are ligands comprising a nitrogen-containing heterocycle, wherein each of L¹, L², L³, L⁴, L⁵, and L⁶ is independently a monodentate ligand or combined with at least one other ligand to form a multidentate ligand; and

wherein at least one of L¹, L², L³, L⁴, L⁵, and L⁶ is covalently coupled to a one of the spacers.

20. 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 backbone,

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

(CR^rR^s)—

, —

O—

, —

S—

, —

S(O)₂NR^k—

, —

OC(O)NR^m—

, —

OC(S)NRⁿ, —

C(O)NR^t—

, and —

NR^u—

, wherein R^k, R^m, Rⁿ, R^r, R^s, R^t, and R^u are independently selected from the group consisting of hydrogen and substituted or unsubstituted alkyl;

a plurality of transition metal complexes, each transition metal complex having the formula;

wherein M is osmium,

L¹ is a ligand comprising a heterocycle and is coordinatively bound to M via a heteroatom of the heterocycle,

L², L³, L⁴, L⁵, and L⁶ are ligands, wherein each of L¹, L², L³, L⁴, L⁵, and L₆ is independently a monodentate ligand or combined with at least one other ligand to form a multidentate ligand, and

wherein at least one of L¹, L², L³, L⁴, L⁵, and L⁶ is covalently coupled to a one of the spacers.

21. The sensor of claim 20, wherein at least four of L¹, L², L³, L⁴, L⁵, and L⁶ are combined to form at least two multidentate ligands selected from the group consisting of substituted and unsubstituted 2,2′

-bipyridines, 2-(2-pyridyl)imidazoles, and 2,2′

-biimidazoles.