Osmium-containing redox mediator

• US 5,589,326 A
• Filed: 12/30/1993
• Issued: 12/31/1996
• Est. Priority Date: 12/30/1993
• Status: Expired due to Term

• Current Assignee: Roche Diabetes Care Inc. (Roche Holding AG)
• Original Assignee: Boehringer Mannheim Corporation
• Inventors: Deng, Zhi D., Sigler, Gerald F., Wilsey, Christopher D., Surridge, Nigel A., McEnroe, Robert J., Muddiman, Rebecca W., Jernigan, Walter W.
• Primary Examiner(s): Wityshyn, Michael G.
• Assistant Examiner(s): Leary, Louise N.
• Application Number:
  US08/180,492
• Time in Patent Office: 1,097 Days
• Field of Search: 435/4, 435/14, 435/24, 435/25, 435/26, 435/817, 424/5, 430/130
• US Class Current: 435/4
• CPC Class Codes: C07F 15/0026 without a metal-carbon linkage
• CPC Class Codes: C12Q 1/004 mediator-assisted
• CPC Class Codes: Y10S 435/817 Enzyme or microbe electrode

Abstract

A new group of Os(II) and Os(III) compounds useful as redox mediators in electrochemical biosensors. These compounds have 1) low oxidation potential, 2) fast reaction kinetics between the electroactive center of an enzyme and the compound, 3) slow oxidation of osmium by oxygen, and 4) excellent solubility in aqueous medium. These mediators are particularly useful as a component of a reagent used in an electrochemical biosensor, wherein the biosensor is useful for measuring analytes from a biological fluid, such as blood.

Claims

1. A compound having the formula:

##STR5## wherein R and R'"'"' are the same or different and are 2,2'"'"'-bipyridyl, 4,4'"'"'-disubstituted-2,2'"'"'-bipyridyl, 5,5'"'"'-disubstituted-2,2'"'"'-bipyridyl, 1,10-phenanthrolinyl, 4,7-disubstituted-1,10-phenanthrolinyl, or 5,6-disubstituted-1,10-phenanthrolinyl, wherein the disubstitution is a methyl, ethyl, or phenyl group,

R and R'"'"' are coordinated to Os at their nitrogen atoms,

R" is hydrogen, methyl or ethyl,

Z is chloro or bromo,

m is +1 or +2,

X is an anion and is chloride, bromide, iodide, fluoride, tetrafluoroborate, perchlorate, nitrate, sulfate, carbonate, or sulfite,

Y is an anion and is chloride, bromide, iodide, fluoride, tetrafluoroborate, perchlorate or nitrate, and

n is 1 or zero,

but when X is sulfate, carbonate, or sulfite, n is zero,

and when m is 1, n is zero and X is not sulfate, carbonate or sulfite,

wherein the aqueous solubility of the compound is greater than about 1 millimolar.

2. The compound of claim 1, wherein R and R'"'"' are the same or different and are 2,2'"'"'-bipyridyl, 4,4'"'"'-disubstituted-2,2'"'"'-bipyridyl, or 5,5'"'"'-disubstituted 2,2'"'"'-bipyridyl, wherein the disubstitution may be a methyl, ethyl, or phenyl group.

3. The compound of claim 2, wherein R" is hydrogen or methyl.

4. The compound of claim 3, wherein Z is chloro.

5. The compound of claim 4, wherein

X is an anion and is chloride, bromide, or tetrafluoroborate,

Y is an anion and is chloride, bromide, or tetrafluoroborate, and

when m is 2, n is 1 and when m is 1, n is zero.

6. The compound of claim 1, wherein R and R'"'"' are 2,2'"'"'-bipyridyl.

7. The compound of claim 6, wherein R" is hydrogen or methyl.

8. The compound of claim 7, wherein Z is chloro.

9. The compound of claim 8, wherein

X is an anion and is chloride, bromide, or tetrafluoroborate,

Y is an anion and is chloride, bromide, or tetrafluoroborate, and

when m is 2, n is 1 and when m is 1, n is zero.

10. The compound of claim 9, wherein

R" is hydrogen,

X is an anion and is chloride or tetrafluoroborate,

Y is an anion and is chloride or tetrafluoroborate, and

when m is 2, n is 1 and when m is 1, n is zero.

11. A compound having the formula:

##STR6## wherein R and R'"'"' are the same or different and are 2,2'"'"'-bipyridyl, 4,4'"'"'-dimethyl-2,2'"'"'-bipyridyl, 4,4'"'"'-diphenyl-2,2'"'"'-bipyridyl, 1,10-phenanthrolinyl, 4,7-dimethyl-1,10-phenanthrolinyl, 4,7-diphenyl-1,10-phenanthrolinyl, or 5,6-dimethyl-1,10-phenanthrolinyl,

R and R'"'"' are coordinated to Os at their nitrogen atoms,

R" is hydrogen, methyl or ethyl,

Z is chloro or bromo,

m is +1 or +2,

X is an anion and is chloride, bromide, iodide, fluoride, tetrafluoroborate, perchlorate, nitrate, sulfate, carbonate, or sulfite,

Y is an anion and is chloride, bromide, iodide, fluoride, tetrafluoroborate, perchlorate or nitrate, and

n is 1 or zero,

but when X is sulfate, carbonate, or sulfite, n is zero,

and when m is 1, n is zero and X is not sulfate, carbonate or sulfite,

wherein the aqueous solubility of the compound is greater than about 1 millimolar.