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WO2001032665A2 - Complexes a ligands de ruthenium metallique - Google Patents

Complexes a ligands de ruthenium metallique Download PDF

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Publication number
WO2001032665A2
WO2001032665A2 PCT/US2000/041758 US0041758W WO0132665A2 WO 2001032665 A2 WO2001032665 A2 WO 2001032665A2 US 0041758 W US0041758 W US 0041758W WO 0132665 A2 WO0132665 A2 WO 0132665A2
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WO
WIPO (PCT)
Prior art keywords
metal ligand
complexes
complex
ligand complex
fluorescent
Prior art date
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Ceased
Application number
PCT/US2000/041758
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English (en)
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WO2001032665A3 (fr
Inventor
Zakir Murtaza
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FLUORRX Inc
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FLUORRX Inc
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Filing date
Publication date
Application filed by FLUORRX Inc filed Critical FLUORRX Inc
Priority to AU37913/01A priority Critical patent/AU3791301A/en
Publication of WO2001032665A2 publication Critical patent/WO2001032665A2/fr
Publication of WO2001032665A3 publication Critical patent/WO2001032665A3/fr
Anticipated expiration legal-status Critical
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
    • C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
    • C07F15/0046—Ruthenium compounds
    • C07F15/0053—Ruthenium compounds without a metal-carbon linkage
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2458/00—Labels used in chemical analysis of biological material
    • G01N2458/40—Rare earth chelates

Definitions

  • This invention relates to metal ligand complexes useful as fluorescent probes in assays for biological molecules and more specifically m immunoassays making use of fluorescence resonance energy transfer (FRET) and fluorescence polarization (FP) techniques.
  • FRET fluorescence resonance energy transfer
  • FP fluorescence polarization
  • Polarization immunoassays using measurements of the fluorescent lifetime of metal ligand complexes is described in US Patent 5.660,991, dated Aug 26, 1997, issued to J.R. Lakowicz, et. al. Successful use of this method is known to be dependent on selection of the complex. Proper selection can give better sensitivity. Selection of the complex is dependant, among other things, upon the size of the analyte. In cases where the analyte is a protein, such as m immunoassays, a complex having a longer fluorescent lifetime will give better results. However, it is known that in every case a high amsotropy value will give better results.
  • metal ligand complexes contain functional groups enabling their conjugation with biological molecules ("biomolecules") such as antibodies and other proteins thus enabling their use m FRET and FP immunoassays
  • biomolecules biological molecules
  • fluorescence properties of these metal ligand complexes differ from each other based on the ligand used and on the group attached to the complex by the ligand.
  • Known metal ligand complexes that can be linked with biomolecules usually produce amsotropy values of less than 0.3. Fluorescent metal ligand complexes that would produce anisotropy values of greater than 0.3 would expand the usefulness of such complexes especially in FP immunoassays. It has been a problem that such complexes have not been known in the past. It is an object of the present invention to overcome this problem.
  • the present invention which, in one aspect, comprises metal ligand complexes that are fluorescent in response to electromagnetic radiation and that include groups for attachment to biological molecules.
  • the invention comprises FRET or FP assays for biological molecules that make use of such complexes.
  • the metal ligand complex of the present invention comprises a transition metal associated with a complement of diamine ligands, one of which is amino reactive for attachment to a biomolecule.
  • the complex of the present invention is Ru(bpy) 2 (dpa)](PF 6 ) 2 ((A) in FIG. 3.)
  • the complex of the present invention is Ru(phen)(aphen)(deebpy)](PF 6 ) 2 ((B) in FIG. 3.)
  • FIG. 1 shows the absorption and emission spectra of Ru(phn)(aphn)(decbpy), one complex according to the present invention, compared with that of Ru(bpy) 2 (dcbpy), a prior art material.
  • FIG. 2 shows the absorption and emission spectra of Ru(bpy) 2 (dpa), another complex according to the present invention, compared with that of Ru(bpy) 2 (dcpy), a prior art material.
  • FIG. 3 shows the structural formula for two complexes according to the present invention: [Ru(phen)(aphen)(deebpy)](PF(;)2 and [Ru(bpy) 2 (dpa)(PFG)2.
  • Table 1 shows the photophysical parameters, measured by well known techniques on the spectrophotometer, for the embodiments of the present invention (as shown in FIG. 3) and those for Ru(bpy)2(dcbpy)](PF ⁇ )2.
  • the complexes (A) and (B) in FIG. 3 according to the present invention have anisotropy values of 0.32 and 0.36. respectively, (maximum possible value is 0.4) compared with 0.24 for the prior art material. Fluorescent lifetimes for the complexes of the present invention are 155 ns and 557 ns compared with 373 ns for the prior art material, confirming that complex (B) of FIG. 3 is more suitable for FP immunoassays than the prior art material for large molecules. While material (A) will to be useful in FP assays for small molecules.
  • the complexes of the present invention are conjugated to an antibody that is specific to an antigen (the target analyte). After labeling to the antibody the complex gives a value of anisotropy, due to the rotational motion of complex and the antibody with which it is conjugated. On adding this labeled antibody to a target antigen, its anisotropy changes because the rotation is further slowed by the increased size of the resulting system (antibody and antigen). The change in the anisotropy value can be use to study information about the target analyte.
  • the molecular weight of the target antigen based on the complex (A) of FIG.
  • these complexes can be used as the donor, and an appropriate acceptor can be selected based on the emission maximum of the chosen complex.
  • these complexes may be attached to the one of antibodies and will act as donors.
  • An acceptor dye can be attached to the other antibody.
  • antigen an analyte
  • these two antibodies bind to the antigen and show energy transfer. The energy transfer is sensed and used to determine the presence or amount of analyte.
  • J.R. Lakowicz in Principles of Fluorescence Spectroscopy Second Edition, Kluwer Academic Press, 1999, page 368-391.
  • metal ligand complex of the present invention may use other transition metals, such as, for example, Os and Re, and these embodiments are intended to be within the scope of the claims, below.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)

Abstract

L'invention concerne un complexe métallique à ligand fluorescent comprenant un métal de transition associé à un complément de ligands diamine, similaires ou différents, l'un d'eux étant un groupe amino susceptible de se lier à des molécules biologiques. La durée de vie étonnamment longue et le coefficient d'anisotropie des complexes les rendent particulièrement utiles dans des analyses de polarisation de fluorescence ainsi que dans des analyses de transfert d'énergie de résonance de la fluorescence.
PCT/US2000/041758 1999-11-01 2000-10-31 Complexes a ligands de ruthenium metallique Ceased WO2001032665A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU37913/01A AU3791301A (en) 1999-11-01 2000-10-31 New ruthenium metal ligand complexes

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US16280799P 1999-11-01 1999-11-01
US60/162,807 1999-11-01

Publications (2)

Publication Number Publication Date
WO2001032665A2 true WO2001032665A2 (fr) 2001-05-10
WO2001032665A3 WO2001032665A3 (fr) 2001-10-11

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PCT/US2000/041758 Ceased WO2001032665A2 (fr) 1999-11-01 2000-10-31 Complexes a ligands de ruthenium metallique

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AU (1) AU3791301A (fr)
WO (1) WO2001032665A2 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103044494A (zh) * 2013-01-21 2013-04-17 中国科学院福建物质结构研究所 钌金属有机聚合物发光材料及其合成与应用
CN103044495A (zh) * 2013-01-21 2013-04-17 中国科学院福建物质结构研究所 钌发光材料及其合成与应用
CN106866990A (zh) * 2017-02-15 2017-06-20 中国科学院福建物质结构研究所 一种具有可见光催化还原co2性能的钌配位聚合物及其制备方法与用途
CN106893108A (zh) * 2017-02-15 2017-06-27 中国科学院福建物质结构研究所 一种利用可见光敏化近红外稀土发光的钌‑钕双金属配位聚合物及其制备方法和用途
CN113461956A (zh) * 2021-05-31 2021-10-01 广东工业大学 一种钌聚合物及其制备方法和pH值检测荧光探针

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5578498A (en) * 1991-05-22 1996-11-26 Behringwerke Ag Metal chelate containing compositions for use in chemiluminescent assays
US5660991A (en) * 1994-10-28 1997-08-26 Lakowicz; Joseph R. Long lifetime anisotropy (polarization) probes for clinical chemistry, immunoassays, affinity assays and biomedical research
AU3488700A (en) * 1999-02-12 2000-08-29 Ljl Biosystems, Inc. Luminescent metal-ligand complexes

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103044494A (zh) * 2013-01-21 2013-04-17 中国科学院福建物质结构研究所 钌金属有机聚合物发光材料及其合成与应用
CN103044495A (zh) * 2013-01-21 2013-04-17 中国科学院福建物质结构研究所 钌发光材料及其合成与应用
CN103044495B (zh) * 2013-01-21 2017-12-12 中国科学院福建物质结构研究所 钌发光材料及其合成与应用
CN103044494B (zh) * 2013-01-21 2018-02-16 中国科学院福建物质结构研究所 钌金属有机聚合物发光材料及其合成与应用
CN106866990A (zh) * 2017-02-15 2017-06-20 中国科学院福建物质结构研究所 一种具有可见光催化还原co2性能的钌配位聚合物及其制备方法与用途
CN106893108A (zh) * 2017-02-15 2017-06-27 中国科学院福建物质结构研究所 一种利用可见光敏化近红外稀土发光的钌‑钕双金属配位聚合物及其制备方法和用途
CN106893108B (zh) * 2017-02-15 2019-04-16 中国科学院福建物质结构研究所 一种利用可见光敏化近红外稀土发光的钌-钕双金属配位聚合物及其制备方法和用途
CN106866990B (zh) * 2017-02-15 2019-06-21 中国科学院福建物质结构研究所 一种具有可见光催化还原co2性能的钌配位聚合物及其制备方法与用途
CN113461956A (zh) * 2021-05-31 2021-10-01 广东工业大学 一种钌聚合物及其制备方法和pH值检测荧光探针

Also Published As

Publication number Publication date
AU3791301A (en) 2001-05-14
WO2001032665A3 (fr) 2001-10-11

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