Redox polymers
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.
1. A method for monitoring a level of an analyte in a subject, the method comprising:
positioning at least a portion of an analyte sensor into a skin of a subject, wherein the analyte sensor comprises:
a working electrode; and
a counter electrode,
wherein the working electrode comprises:
a non-conductive base material;
a conductive layer disposed on the base material; and
reagent positioned on the conductive layer, the reagent comprising a polymeric transition metal complex comprising:
a transition metal complex comprising the formula:
wherein M is a transition metal;
L 1 is a ligand comprising a heterocycle and is coordinatively bound to M via a heteroatom of the heterocycle;
L 2 , L 3 , L 4 , L 5 , and L 6 are ligands comprising a nitrogen-containing heterocycle, wherein each of L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 is independently a monodentate ligand or is combined with at least one other ligand to form a multidentate ligand; and
wherein at least one of L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 is covalently coupled to the at least one spacer;
a polymer backbone; and
at least one spacer covalently coupled to the polymer backbone, the at least one spacer comprising at least one non-cyclic functional group selected from the group consisting of —(CR r R s )—, —O—, —S—, —C(O)O—, —S(O) 2 NR k —, —OC(O)NR m —, —OC(S)NR n , —C(O)NR t —, —CR v ═N—O—, —CR w ═NNR x —, and —(SiR y R z )—, and 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 , R n , R t , R u , R v , R w , R x , R y , and R z are independently hydrogen or substituted or unsubstituted alkyl, wherein the transition metal complex is covalently coupled to the spacer;
determining a level of an analyte over a period of time from signals generated by the analyte sensor,
wherein the determining over a period of time provides for monitoring the level of the analyte in the subject.
2. The method of claim 1 , further comprising an analyte-responsive enzyme.
3. The method of claim 2 , wherein the analyte-responsive enzyme is an enzyme selected from the group consisting of glucose oxidase and glucose dehydrogenase.
4. The method of claim 2 , wherein the analyte-responsive enzyme is covalently coupled to the polymer backbone.
5. The method of claim 1 , wherein the polymer backbone comprises a nitrogen containing heterocyclic ring.
6. The method of claim 1 , wherein the spacer comprises —C(O)NR t —.
7. The method of claim 1 , wherein the nitrogen-containing heterocycle comprises a substituted or unsubstituted pyridine, imidazole, 2,2′-bipyridine, 2-(2-pyridyl)imidazole, or 2,2′-biimidazole.
8. The method of claim 1 , wherein at least two of L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 are combined to form at least one multidentate ligand.
9. The method of claim 1 , wherein at least four of L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 are combined to form at least two multidentate ligand.
10. The method of claim 1 , wherein at least four of L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 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.
11. The method of claim 10 , wherein the transition metal complex comprises at least one substituted or unsubstituted 2,2′-biimidazole or 2-(2-pyridyl)imidazole.
12. The method of claim 1 , wherein the polymer is crosslinked.
13. The method of claim 1 , wherein the transition metal complex has the formula:
wherein M is a transition metal;
R 1 and R 2 are independently substituted or unsubstituted alkyl;
R 3 , R 4 , R 5 , and R 6 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 method of claim 1 , wherein the transition metal complex has the formula:
wherein M is a transition metal;
R′ 1 are substituted or unsubstituted alkyl;
R′ 3 and R′ 4 and 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, —CO 2 H, —SO 3 H, —NO 2 , —NH 2 , —NHNH 2 , —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 method of claim 1 , wherein the transition metal complex has the formula:
wherein M is a transition metal;
R 18 and R 21 are independently —H, —F, —Cl, —Br, —CN, —CO 2 H, —SO 3 H, —NO 2 , —NH 2 , —NHNH 2 , —SH, or substituted or unsubstituted C1 to C12 alkylamino, C2 to C24 dialkylamino, C1 to C12 alkoxy, or C1 to C12 alkyl;
R 16 , R 17 , R 19 , R 20 , R 22 and R 23 —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. The method of claim 1 , wherein the spacer comprises —(CR r R s )—, wherein R r and R s are independently hydrogen, chlorine, fluorine, or substituted or unsubstituted alkyl, alkoxy, alkenyl, or alkynyl.
17. The method of claim 1 , wherein the spacer comprises —O— or —S—.
18. The method of claim 1 , wherein the spacer comprises —C(O)O— or —S(O) 2 NR k —, wherein R k , is hydrogen or substituted or unsubstituted alkyl.
19. The method of claim 1 , wherein the spacer comprises —CR v ═N—O— or —CR w ═NNR x —, wherein R v , is hydrogen or substituted or unsubstituted alkyl and wherein R w and R x are independently hydrogen or substituted or unsubstituted alkyl.
20. The method of claim 1 , wherein the spacer comprises —(SiR y R z )—, wherein R y and R z are independently hydrogen or substituted or unsubstituted alkyl.