Luminescent lanthanide complexes

• US 7,517,701 B2
• Filed: 10/14/2005
• Issued: 04/14/2009
• Est. Priority Date: 09/30/2004
• Status: Expired due to Fees

• Current Assignee: Molecular Devices
• Original Assignee: MDS Analytical Technologies US Incorporated (Danaher Corporation)
• Inventors: Atkinson, Paul, Kielar, Filip, Gaudet, Elizabeth, Yi, George G., Parker, David, Boge, Annegret, Sportsman, J. Richard
• Primary Examiner(s): Shibuya; Mark L.
• Assistant Examiner(s): Haq; Shafiqul
• Application Number:
  US11/250,722
• Publication Number:
  US 20070087452A1
• Time in Patent Office: 1,278 Days
• Field of Search: 534/10, 534/15, 534/16, 436/546, 436/172, 436/544, 436/56, 436/81, 435/6, 435/7.5, 435/188, 530/391.5
• US Class Current: 436/546
• CPC Class Codes: C07D 403/02 containing two hetero rings
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 471/14 Ortho-condensed systems
• CPC Class Codes: C07D 491/04 Ortho-condensed systems
• CPC Class Codes: C07D 495/04 Ortho-condensed systems
• CPC Class Codes: C09B 57/10 Metal complexes of organic compounds not being dyes in uncomplexed form
• CPC Class Codes: G01N 2458/40 Rare earth chelates
• CPC Class Codes: G01N 33/582 with fluorescent label
• CPC Class Codes: Y10T 436/13 Tracers or tags

Abstract

Systems, including compositions, kits, and methods, particularly for photoluminescence applications. The systems may include, among others, (1) organic chelators, (2) complexes between the chelators and lanthanide ions, and (3) precursors, derivatives, and uses thereof. The chelators may include a 1,4,7,10-tetraazacyclododecane ring system, for example, having the formula:

Here, R¹, R², and R³ are substituents of the tetraazacyclododecane ring system, that is further substituted at the 10-position by a sensitizer Z that is typically a polyheterocyclic ring system. The organic chelator may be capable of forming a luminescent complex with a lanthanide ion, and is optionally further substituted by a reactive functional group or a conjugated substance. The resulting lanthanide complex may be useful in luminescence-based assays, such as energy transfer assays, among others.

Claims

1. A luminophore comprising a chelator, a polycyclic heteroaromatic sensitizer moiety, and a lanthanide, the luminophore having the formula

2. The luminophore of claim 1, where the luminophore is further substituted by one or more reactive functional groups or conjugated substances.

3. The luminophore of claim 2, where each reactive functional group or conjugated substance is independently bound to the luminophore via a covalent linking moiety.

4. The luminophore of claim 2 where the reactive functional group or conjugated substance is a substituent on the polycyclic heteroaromatic sensitizer moiety.

5. The luminophore of claim 2, where the conjugated substance is a member of a specific binding pair.

6. The luminophore of claim 3, where at least one of the covalent linking moieties includes a linkage metal.

7. The luminophore of claim 6, where at least one of the covalent linking moieties includes a metal-binding functional group that binds to the linkage metal.

8. The luminophore of claim 7, where the metal-binding functional group is a phosphate, sulfonic acid, or carboxylic acid functional group.

9. The luminophore of claim 6, where the linkage metal is aluminum, iron, or gallium.

10. The luminophore of claim 7, where the metal-binding functional group is a phosphate functional group, and the linkage metal is gallium(III).

11. A method of staining a sample, comprising:

combining a luminophore according to claim 1 with the sample; and

illuminating the combined sample under conditions that elicit an optical response from the luminophore.

12. The method of claim 11, further comprising comparing the optical response with a standard or expected response.

13. The method of claim 11, where the luminophore is further substituted by one or more reactive functional groups or conjugated substances.

14. The method of claim 13, where each reactive functional group or conjugated substance is bound to the luminophore via a covalent linking moiety.

15. The method of claim 14 where the reactive functional group or conjugated substance is a substituent on the polycyclic heteroaromatic sensitizer moiety.

16. The method of claim 13, where the conjugated substance is a member of a specific binding pair.

17. The method of claim 11 further comprising bringing the sample into contact with an energy transfer donor or an energy transfer acceptor capable of participating in luminescence energy transfer with the luminophore.

18. The method of claim 17, where the sample is brought into contact with an energy transfer acceptor capable of accepting energy transfer from the luminophore.

19. The luminophore of claim 4, where the polycyclic heteroaromatic sensitizer moiety is further substituted at one or more positions by alkyl, alkoxy, halogen, carboxylic acid, sulfonic acid, or phosphonate.

20. A luminophore comprising a chelator, a lanthanide ion, and a sensitizer moiety, the luminophore having the formula

21. The luminophore of claim 20, where the sensitizer moiety is further substituted at one or more positions by alkyl, alkoxy, halogen, carboxylic acid, sulfonic acid, or phosphonate.

22. The luminophore of claim 20, where the complexed lanthanide metal M is selected from cerium (Ce), praseodymium (Pr), neodymium (Nd), promethium (Pm), samarium (Sm), europium (Eu), gadolinium (Gd), terbium (Tb), dysprosium (Dy), holmium (Ho), erbium (Er), thulium (Tm), ytterbium (Yb), and lutetium (Lu).

23. The luminophore of claim 22, where the complexed lanthanide metal M is selected from terbium, europium, dysprosium, and samarium.

24. The luminophore of claim 22, where the complexed lanthanide metal M is terbium.

25. The luminophore of claim 20, where the luminophore is further substituted by one or more reactive functional groups or conjugated substances.

26. A method of staining a sample, comprising:

combining a luminophore according to claim 20 with the sample; and

illuminating the sample under conditions that elicit an optical response.