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US 8,618,293 B2Granted
Redox mediators
AssigneeRoche Diagnostics Operations, Inc.
InventorsChristopher Paul Newman, Luet Lok Wong, Hugh Allen Oliver Hill, Tai-Chu Lau
Life of this patent
Estimating the term…
Abstract
The present invention relates to ruthenium and osmium complexes of Formula [M(A)w(B)x(C)y]m(Xz)n, per se and the use of ruthenium and osmium complexes of Formula I as redox mediators in electrochemical biosensors.
Claims14
A method for measuring an amount or concentration of an analyte, comprising:
- (a) contacting a sample which contains the analyte with a solution containing an enzyme that acts on the analyte and a redox mediator of Formula I
- [M(A)w(B)x(C)y]m(Xz)n Formula I
- wherein
- M is ruthenium or osmium and has an oxidation state of 0, 1, 2, 3 or 4;
- each of w, x, and y is an integer independently selected from the integers 1 to 4;
- m is an integer selected from the integers −5 to +4;
- n is an integer selected from selected from the integers 1 to 5;
- z is an integer selected from the integers −2 to +1;
- A is a monodentate 5- or 6-membered aromatic ligand containing 1, 2 or 3 nitrogen atoms which is optionally substituted by 1 to 8 substituents each selected from the group consisting of substituted or unsubstituted alkyl, alkenyl, or aryl groups, —F, —Cl, —Br, —I, —NO2, —CN, —CO2H, —SO3H, —NHNH2, —SH, aryl, alkoxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, —OH, alkoxy, —NH2, alkylamino, dialkylamino, alkanoylamino, arylcarboxamido, hydrazino, alkylhydrazino, hydroxylamino, alkoxyamino and alkylthio or A is NCS;
- B is a bi-, tri-, tetra-, penta- or hexadentate ligand which is linear having the formula R1RN(C2H4NR)wR1 or cyclic having the formula (RNC2H4)v, (RNC2H4)p(RNC3H6)q or [(RNC2H4)(RNC3H6)]s, wherein
- w is an integer selected from the integers 1-5,
- v is an integer selected from the integers 3-6,
- each of p and q is an integer independently selected from the integers 1-3 whereby the sum of p and q is 4, 5 or 6,
- s is either 2 or 3;
- and each of R and R1 is independently hydrogen or alkyl;
- C is a ligand other than B;
- and
- X is a counter ion, wherein the number of coordinating atoms is 6, with the exception of [RuIII(Me3tacn)(acac)(py)](NO3)2);
- (b) incubating the contacted sample under conditions that cause the enzyme to act on the analyte;
- (c) subjecting the incubated sample of step (b) to conditions which result in a change in a measurable signal;
- and
- (d) measuring the measurable signal to determine the amount or concentration of the analyte in the sample.
19 more elements
A complex according to Formula I
- [M(A)w(B)x(C)y]m(XZ)n Formula 1
- wherein
- M is ruthenium or osmium and has an oxidation state of 0, 1, 2, 3 or 4;
- each of w, x, and y is an integer independently selected from the integers 1 to 4;
- m is an integer selected from the integers −5 to +4;
- n is an integer selected from selected from the integers 1 to 5;
- z is an integer selected from the integers −2 to +1;
- A is a monodentate 5- or 6-membered aromatic ligand containing 1, 2 or 3 nitrogen atoms which is optionally substituted by 1 to 8 substituents each selected from the group consisting of substituted or unsubstituted alkyl, alkenyl, or aryl groups, —F, —Cl, —Br, —I, —NO2, —CN, —CO2H, —SO3H, —NHNH2, —SH, aryl, alkoxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, —OH, alkoxy, —NH2, alkylamino, dialkylamino, alkanoylamino, arylcarboxamido, hydrazino, alkylhydrazino, hydroxylamino, alkoxyamino and alkylthio;
- B is a bi-, tri-, tetra-, penta- or hexadentate ligand which is linear having the formula R1RN(C2H4NR)wR1 or cyclic having the formula (RNC2H4)v, (RNC2H4)p(RNC3H6)q or [(RNC2H4)(RNC3H6)]s, wherein
- w is an integer selected from the integers 1-5,
- v is an integer selected from the integers 3-6,
- each of p and q is an integer independently selected from the integers 1-3 whereby the sum of p and q is 4, 5 or 6,
- s is either 2 or 3 and
- each of R and R1 is independently hydrogen or alkyl;
- C is a ligand other than A or B;
- and
- X is a counter ion,
- wherein the number of coordinating atoms is 6, with the exception of [RuIII(Me3tacn)(acac)(Py)](NO3)2;
- and
- wherein the complex is selected from the group consisting of [RuIII(1,4,7-trimethyl-1,4,7-triazacyclononane)(acac)(N-methylimidazole)](NO3)2, [RuIII(1,4,7-trimethyl-1,4,7-triazacyclononane)(acac)(4-methylpyridine)]Cl2, [RuIII(1,4,7-trimethyl-1,4,7-triazacyclononane)(acac)(3-chloropyridine)](NO3)2, [RuIII(1,4,7-trimethyl-1,4,7-triazacyclononane)(acac)(isonicotinamide)](NO3)2, [RuIII(1,4,7-trimethyl-1,4,7-triazacyclononane)(acac)pyrazine](NO3)2, [RuIII(1,4,7-trimethyl-1,4,7-triazacyclononane)(acac)(4-methoxypyridine)](NO3)2, [RuIII(1,4,7-trimethyl-1,4,7-triazacyclononane)(acac)(4-dimethylaminopyridine)](NO3)2, [RuIII(1,4,7-trimethyl-1,4,7-triazacyclononane)(acac)(4-t-butyl-pyridine)](NO3)2, [RuIII(1,4,7-trimethyl-1,4,7-triazacyclononane)(acac)(isoquinoline)](NO3)2, [RuIII(1,4,7-trimethyl-1,4,7-triazacyclononane)(tropolone)(pyridine)](NO3)2, [RuIII(1,4,7-trimethyl-1,4,7-triazacyclononane)(tropolone)(4-t-butyl-pyridine)](NO3)2, [RuIII(1,4,7-trimethyl-1,4,7-triazacyclononane)(acac)(3,4-dimethylpyridine)](CF3SO3)2, and [RuIII(1,4,7-trimethyl-1,4,7-triazacyclononane)(acac)(3-hydroxypyridine)](NO3)2.
17 more elements
A complex according to Formula I
- [M(A)w(B)x(C)y]m(XZ)n Formula 1
- wherein
- M is ruthenium or osmium and has an oxidation state of 0, 1, 2, 3 or 4;
- each of w, x, and y is an integer independently selected from the integers 1 to 4;
- m is an integer selected from the integers −5 to +4;
- n is an integer selected from selected from the integers 1 to 5;
- z is an integer selected from the integers −2 to +1;
- A is a monodentate 5- or 6- membered aromatic ligand containing 1, 2 or 3 nitrogen atoms which is optionally substituted by 1 to 8 substituents each selected from the group consisting of substituted or unsubstituted alkyl, alkenyl, or aryl groups, —F, —Cl, —Br, —I, —NO2, —CN, —CO2H, —SO3H, -NHNH2, —SH, aryl, alkoxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, —OH, alkoxy, —NH2, alkylamino, dialkylamino, alkanoylamino, arylcarboxamido, hydrazino, alkylhydrazino, hydroxylamino, alkoxyamino and alkylthio;
- B is a bi-, tri-, tetra-, penta- or hexadentate ligand which is linear having the formula R1RN(C2H4NR)wR1 or cyclic having the formula (RNC2H4)v, (RNC2H4)p(RNC3H6)q or [(RNC2H4)(RNC3H6)]s, wherein
- w is an integer selected from the integers 1-5,
- v is an integer selected from the integers 3-6,
- each of p and q is an integer independently selected from the integers 1-3 whereby the sum of p and q is 4, 5 or 6,
- s is either 2 or 3 and
- each of R and R1 is independently hydrogen or alkyl;
- C is a ligand other than A or B;
- and
- X is a counter ion,
- wherein the number of coordinating atoms is 6, with the exception of [RuIII(Me3tacn)(acac)(Py)](NO3)2;
- and
- wherein the complex is selected selected from the group consisting of [RuIII(1,4,7-trimethyl-1,4,7-triazacyclononane)(acac)(N-methylimidazole)](PF6)2 and RuIII(1,4,7-trimethyl-1,4,7-triazacyclononane)(acac)(N-methylimidazole)](NO3)2.
17 more elements
A complex according to Formula 1
- [M(A)w(B)x(C)y]m(XZ)n Formula 1
- wherein
- M is ruthenium or osmium and has an oxidation state of 0, 1, 2, 3 or 4;
- each of w, x, and y is an integer independently selected from the integers 1 to 4;
- m is an integer selected from the integers −5 to +4;
- n is an integer selected from selected from the integers 1 to 5;
- z is an integer selected from the integers −2 to +1;
- A is a monodentate 5- or 6-membered aromatic ligand containing 1, 2 or 3 nitrogen atoms which is optionally substituted by 1 to 8 substituents each selected from the group consisting of substituted or unsubstituted alkyl, alkenyl, or aryl groups, —F, —Cl, —Br, —I, —NO2, —CN, —CO2H, —SO3H, —NHNH2, —SH, aryl, alkoxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, —OH, alkoxy, —NH2, alkylamino, dialkylamino, alkanoylamino, arylcarboxamido, hydrazino, alkylhydrazino, hydroxylamino, alkoxyamino and alkylthio;
- B is a bi-, tri-, tetra-, penta- or hexadentate ligand which is linear having the formula R1RN(C2H4NR)wR1 or cyclic having the formula (RNC2H4)v, (RNC2H4)p(RNC3H6)q or [(RNC2H4)(RNC3H6)]s, wherein
- w is an integer selected from the integers 1-5,
- v is an integer selected from the integers 3-6,
- each of p and q is an integer independently selected from the integers 1-3 whereby the sum of p and q is 4, 5 or 6,
- s is either 2 or 3 and
- each of R and R1 is independently hydrogen or alkyl;
- C is a ligand other than A or B;
- and
- X is a counter ion,
- wherein the number of coordinating atoms is 6, with the exception of [RuIII(Me3tacn)(acac)(Py)](NO3)2;
- and
- wherein ligand A is selected from the group consisting of guanine, adenine, a 5-membered heteroaromatic comprising three nitrogen atoms in the ring, a 6-membered heteroaromatic comprising three nitrogen atoms in the ring, imidazole, pyrazole, thiazole, oxazole, and isomers thereof.
17 more elements
A complex according to Formula I
- [M(A)w(B)x(C)y]m(XZ)n Formula 1
- wherein
- M is ruthenium or osmium and has an oxidation state of 0, 1, 2, 3 or 4;
- each of w, x, and y is an integer independently selected from the integers 1 to 4;
- m is an integer selected from the integers −5 to +4;
- n is an integer selected from selected from the integers 1 to 5;
- z is an integer selected from the integers −2 to +1;
- A is a monodentate 5- or 6-membered aromatic ligand containing 1, 2 or 3 nitrogen atoms which is optionally substituted by 1 to 8 substituents each selected from the group consisting of substituted or unsubstituted alkyl, alkenyl, or aryl groups, —F, —Cl, —Br, —I, —NO2, —CN, —CO2H, —SO3H, —NHNH2, —SH, aryl, alkoxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, —OH, alkoxy, —NH2, alkylamino, dialkylamino, alkanoylamino, arylcarboxamido, hydrazino, alkylhydrazino, hydroxylamino, alkoxyamino and alkylthio;
- B is a bi-, tri-, tetra-, penta- or hexadentate ligand which is linear having the formula R1RN(C2H4NR)wR1 or cyclic having the formula (RNC2H4)v, (RNC2H4)p,(RNC3H6)q or [(RNC2H4)(RNC3H6)]s, wherein
- w is an integer selected from the integers 1-5,
- v is an integer selected from the integers 3-6,
- each of p and q is an integer independently selected from the integers 1-3 whereby the sum of p and q is 4, 5 or 6,
- s is either 2 or 3 and
- each of R and R1 is independently hydrogen or alkyl;
- C is a ligand other than A or B;
- and
- X is a counter ion,
- wherein the number of coordinating atoms is 6, with the exception of [RuIII(Me3tacn)(acac)(Py)](NO3)2;
- and
- wherein B is selected from the group consisting of 1,4,7-trimethyl-1,4,7-triazacyclononane, 1,1,4,7,10,10-hexamethyltriethylenetetramine, 1,2-dimethylethylenediamine and 1,1,2,2-tetramethylethylenediamine.
17 more elements
Dependencies are inferred from the claim text.