Luminescent 1-hydroxy-2-pyridinone chelates of lanthanides

• US 9,556,122 B2
• Filed: 10/08/2013
• Issued: 01/31/2017
• Est. Priority Date: 07/10/2006
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Raymond, Kenneth N., Xu, Jide, Moore, Evan G., Werner, Eric J.
• Primary Examiner(s): KOSACK, JOSEPH R
• Application Number:
  US14/048,475
• Publication Number:
  US 20140039169A1
• Time in Patent Office: 1,211 Days
• US Class Current: 1/1
• CPC Class Codes: C07D 213/89 with hetero atoms directly attached to the ring nitrogen atom
• CPC Class Codes: C07D 217/26 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C09K 11/06 containing organic luminescent materials
• CPC Class Codes: C09K 2211/1022 bridged by heteroatoms, e.g. N, P, Si or B
• CPC Class Codes: C09K 2211/1029 containing one nitrogen atom as the heteroatom
• CPC Class Codes: C09K 2211/1044 containing two nitrogen atoms as heteroatoms
• CPC Class Codes: C09K 2211/1088 containing oxygen as the only heteroatom
• CPC Class Codes: C09K 2211/185 of the platinum group, i.e. Os, Ir, Pt, Ru, Rh or Pd
• CPC Class Codes: H05B 33/14 characterised by the chemical or physical composition or the arrangement of the electroluminescent material , or by the simultaneous addition of the electroluminescent material in or onto the light source

Abstract

The present invention provides luminescent complexes between a lanthanide ion and an organic ligand which contains 1,2-hydroxypyridinone units. The complexes of the invention are stable in aqueous solutions and are useful as molecular probes, for example in medical diagnostics and bioanalytical assay systems. The invention also provides methods of using the complexes of the invention.

Claims

1. A compound having the structure:

2. The compound according to claim 1, wherein the scaffold moiety is a member selected from substituted or unsubstituted alkyl and substituted or unsubstituted heteroalkyl.

3. The compound according to claim 1, wherein at least one of Z, Y¹, Y², L¹, and L² is substituted with a functional moiety.

4. The compound according to claim 1, wherein Z is O, and L and L² are each ethyl.

5. The compound according to claim 1, wherein said targeting moiety comprises a member selected from a small-molecule ligand, a peptide, a protein, a fusion protein, an enzyme, an antibody, an antibody fragment, an antigen, a nucleic acid, a carbohydrate, a lipid, and a pharmacologically active molecule.

6. The compound according to claim 1, wherein said reactive functional group is a member selected from —

OH, —

SH, —

NH₂, —

C(O)NHNH₂ (hydrazide), maleimide, activated ester, aldehyde, ketone, hydroxylamine, imidoester, isocyanate, isothiocyanate, sulfonylchloride, acylhalide, and —

COOY, wherein Y is a member selected from H, a negative charge and a salt counter-ion.

7. The compound according to claim 1, wherein the functional moiety is a member selected from:

8. The compound according to claim 1, wherein said functional moiety has the structure:

9. The compound according to claim 1, wherein said functional moiety comprises a polyether.

10. The compound according to claim 9, wherein said polyether is a member selected from polyethylene glycol (PEG) and derivatives thereof.

11. The compound according to claim 10, wherein said polyether has a molecular weight of about 50 to about 10,000 daltons.

12. The compound according to claim 1, having a structure selected from:

13. A complex comprising a compound according to claim 1 and a metal ion.

14. The complex according to claim 13, wherein said metal ion is selected from a lanthanide ion, an actinide ion, and a transition metal ion.

15. The complex according to claim 14, wherein said lanthanide ion is selected from La³⁺, Nd³⁺, Sm³⁺, Eu³⁺, Gd³⁺, Tb³⁺, Dy³⁺, Er³⁺, Tm³⁺, Yb³⁺, and Lu³⁺.

16. The complex according to claim 14, wherein said actinide ion is selected from U⁶⁺, Np⁴⁺, Np⁵⁺, Pu⁴⁺, and Am³⁺.

17. The complex according to claim 14, wherein said transition metal ion is Fe³⁺.

18. The complex according to claim 13, wherein the metal is a radioactive isotope.