DOE Patents title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Luminescent 1-hydroxy-2-pyridinone chelates of lanthanides


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.

; ; ;
Issue Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
OSTI Identifier:
Patent Number(s):
Application Number:
Patent Classifications (CPCs):
DOE Contract Number:  
Resource Type:
Resource Relation:
Patent File Date: 2013 Oct 08
Country of Publication:
United States

Citation Formats

Raymond, Kenneth N., Xu, Jide, Moore, Evan G., and Werner, Eric J. Luminescent 1-hydroxy-2-pyridinone chelates of lanthanides. United States: N. p., 2017. Web.
Raymond, Kenneth N., Xu, Jide, Moore, Evan G., & Werner, Eric J. Luminescent 1-hydroxy-2-pyridinone chelates of lanthanides. United States.
Raymond, Kenneth N., Xu, Jide, Moore, Evan G., and Werner, Eric J. Tue . "Luminescent 1-hydroxy-2-pyridinone chelates of lanthanides". United States.
title = {Luminescent 1-hydroxy-2-pyridinone chelates of lanthanides},
author = {Raymond, Kenneth N. and Xu, Jide and Moore, Evan G. and Werner, Eric J.},
abstractNote = {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.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {2017},
month = {1}

Works referenced in this record:

2,3-Dihydroxybenzoic acid amides of tetraazaalkanes and tetaaza cycloalkanes
patent, January 1980

In vitro removal of actinide (IV) ions
patent, January 1982

Polycatecholamide chelating agents
patent, April 1984

Pharmaceutical compositions of hydroxypyridones
patent, May 1987

Hydroxypyridonate chelating agents
patent, October 1987

Aryl substituted aminomethyl benzene derivatives having antiarrhythmic utility
patent, May 1988

Method of detecting electrophoretically separated oligonucleotides
patent, August 1989

Analyte detection by means of energy transfer
patent, September 1989

Template synthesis of macrocyclic catecholamide complexes
patent, July 1990

Imaging agents for in vivo magnetic resonance and scintigraphic imaging
patent, April 1991

patent, September 1991

2,3-dihydroxyterephthalamides as highly effective metal ion sequestering compounds
patent, September 1991

Macrocyclic congugates and their use as diagnostic and therapeutic agents
patent, July 1995

Storage-stable solutions of accelerator systems
patent, November 1995

Antibodies to the HRPII protein of plasmodium falciparum
patent, December 1995

3-hydroxy-2(1H)-pyridinone chelating agents
patent, April 1997

Cascade polymer complexes, process for their production and pharamceutical agents containing said complexes
patent, October 1998

3-hydroxy-2(1H)-pyridinone chelating agents
patent, April 1999

Homogeneous luminescence assay method based on energy transfer
patent, December 1999

Polymeric membranes functionalized with polyhydroxypyridinone ligands
patent, April 2001

Salicylamide-lanthanide complexes for use as luminescent markers
patent, June 2002

Phthalamide lanthanide complexes for use as luminescent markers
patent, February 2003

Hydroxypyridonate and hydroxypyrimidinone chelating agents
patent, January 2005

Phthalamide-lanthanide complexes for use as luminescent markers
patent, March 2005

Salicylamide-lanthanide complexes for use as luminescent markers
patent, March 2006

Salicylamide-lanthanide complexes for use as luminescent markers
patent, July 2008

Phthalamide-lanthanide complexes for use as luminescent markers
patent, October 2008

Hydroxypyridonate and hydroxypyrimidinone chelating agents
patent, May 2010

Radionuclides for medical use
patent, September 2010

Luminescent macrocyclic lanthanide complexes
patent, May 2012

Multi-color time resolved fluorophores based on macrocyclic lanthanide complexes
patent, August 2013

Aromatic triamide-lanthanide complexes
patent, October 2013

Luminescent 1-hydroxy-2-pyridinone chelates of lanthanides
patent, October 2013

Luminescent macrocyclic lanthanide complexes
patent, May 2014

Phthalamide-lanthanide complexes for use as luminescent markers
patent-application, September 2002

Phthalamide lanthanide complexes for use as luminescent markers
patent-application, December 2002

Macrocyclic module compositions
patent-application, October 2003

Hydroxypyridonate and hydroxypyrimidinone chelating agents
patent-application, January 2005

Phthalamide-lanthanide complexes for use as luminescent markers
patent-application, March 2005

Reagent system and method for modifying the luminescence of lanthanide(III) macrocyclic complexes
patent-application, June 2007

Multi-Color Time Resolved Fluorophores Based on Macrocyclic Lanthanide Complexes
patent-application, September 2008

Luminescent Macrocyclic Lanthanide Complexes
patent-application, September 2008

Phthalamide-Lanthanide Complexes for Use as Luminescent Markers
patent-application, January 2009

Aromatic Triamide-Lanthanide Complexes
patent-application, February 2009

Luminescent 1-Hydroxy-2-Pyridinone Chelates of Lanthanides
patent-application, January 2010

Multi-color Time Resolved Fluorophores Based on Macrocyclic Lanthanide Complexes
patent-application, July 2010

Radiopharmaceutical Complexes
patent-application, August 2011

Combination Treatment of Hydroxpyridonate Actinide/Lanthanide Decorporation Agents
patent-application, August 2012

Determination of the Prototropic Exchange Rate at the Water Molecule Coordinated to an Anionic Paramagnetic GdIII Chelate
journal, September 1998

Nouvelle méthode de synthèse du 3,4,3 LI 1,2 HOPO (1,5,10,14-tétra (1-hydroxy-2-pyridone-6 oyl) 1,5,10,14 tétraazatétradécane) [A new synthesis of 3,4,3 LI 1,2 HOPO]
journal, April 1998

Synthesis and relaxometry of high-generation (G = 5, 7, 9, and 10) PAMAM dendrimer-DOTA-gadolinium chelates
journal, February 1999

Study of metal complexes of a tripodal hydroxypyridinone ligand by electrospray tandem mass spectrometry
journal, June 2005

  • Budimir, Natali; Fournier, Françoise; Bailly, Théodorine
  • Rapid Communications in Mass Spectrometry, Vol. 19, Issue 13, p. 1822-1828

Synthesis of 3,4,3 LI 1,2 HOPO labelled with 14C: Synthesis of 3,4,3
journal, February 2001

New compounds of tetradentate Schiff bases with vanadium(IV) and vanadium(V) †
journal, January 1999

  • Choudhary, Nosheen F.; Connelly, Neil G.; Hitchcock, Peter B.
  • Journal of the Chemical Society, Dalton Transactions, Issue 24, p. 4437-4446

Syntheses and Relaxation Properties of Mixed Gadolinium Hydroxypyridinonate MRI Contrast Agents
journal, December 2000

Detection of pulmonary emboli by using MR angiography with MPEG-PL-GdDTPA: an experimental study in rabbits.
journal, May 1994

Synthesis of a Ligand Based upon a New Entry into the 3-Hydroxy-N-alkyl-2(1H)-pyridinone Ring System and Thermodynamic Evaluation of Its Gadolinium Complex
journal, June 2000

Tris(pyrone) Chelates of Gd(III) as High Solubility MRI-CA
journal, February 2006

Next Generation, High Relaxivity Gadolinium MRI Agents
journal, December 2004

Oxygen‐17 NMR and EPR studies of water exchange from the first coordination sphere of gadolinium(III) aquoion and gadolinium(III) propylenediaminetetra‐acetate
journal, December 1980

  • Southwood‐Jones, Rosalind V.; Earl, William L.; Newman, Kenneth E.
  • The Journal of Chemical Physics, Vol. 73, Issue 12, p. 5909-5918

Rational reduction of the conformational space of a siderophore analog through nonbonded interactions: the role of entropy in enterobactin
journal, July 1993

A solid-state study of eight-coordinate lanthanide(iii) complexes (Ln = Eu, Gd, Tb, Dy) with 1-hydroxy-2-pyridinone
journal, March 2003

Specific sequestering agents for the actinides. 21. Synthesis and initial biological testing of octadentate mixed catecholate-hydroxypyridinonate ligands
journal, February 1993

Gadolinium-containing copolymeric chelates—a new potential MR contrast agent
journal, August 1999

  • Unger, Evan C.; Shen, Dekang; Wu, Guanli
  • Magma: Magnetic Resonance Materials in Physics, Biology, and Medicine, Vol. 8, Issue 3, p. 154-162

Force Field Parametrization for Gadolinium Complexes Based on ab Initio Potential Energy Surface Calculations
journal, April 2000

Highly Soluble Tris-hydroxypyridonate Gd(III) Complexes with Increased Hydration Number, Fast Water Exchange, Slow Electronic Relaxation, and High Relaxivity1
journal, February 2007

Specific sequestering agents for the actinides. 16. Synthesis and initial biological testing of polydentate oxohydroxypyridinecarboxylate ligands
journal, January 1988

Gadolinium complex of tris[(3-hydroxy-1-methyl- 2-oxo-1,2-didehydropyridine-4-carboxamido)ethyl]-amine: A New Class of gadolinium magnetic resonance relaxation agents
journal, July 1995

Gadolinium(III) 1,2-Hydroxypyridonate-Based Complexes: Toward MRI Contrast Agents of High Relaxivity1
journal, September 2004

Paramagnetic GdIIIFeIII heterobimetallic complexes of DTPA-bis-salicylamide
journal, August 1993

A family of novel DNA sequencing instruments based on single-photon detection
journal, August 2002

A Time-Resolved Fluorescence Immunoassay (DELFIA) Increases the Sensitivity of Antigen-Driven Cytokine Detection
journal, January 2003

Luminescence Probes: The Eu3⊕- and Tb3⊕-Cryptates of Polypyridine Macrobicyclic Ligands
journal, December 1987

Radiometal-Labeled Agents (Non-Technetium) for Diagnostic Imaging
journal, September 1999

Synthesis of macrocyclic polyhydroxy tetralactams derived from L-tartaric acid and β-hydroxyglutaric acid
journal, October 1997

Photocleavage of a 2-nitrobenzyl linker bridging a fluorophore to the 5' end of DNA
journal, January 2003

Luminescence imaging microscopy and lifetime mapping using kinetically stable lanthanide(III) complexes
journal, September 2000

Development of radioimmunotherapeutic and diagnostic antibodies: an inside-out view
journal, October 2007

Semiconductor Nanocrystals as Fluorescent Biological Labels
patent, September 1998

Rapid DNA sequencing by horizontal ultrathin gel electrophoresis
journal, August 1991

Towards materials with planned properties: dinuclear f-f helicates and d-f non-covalent podates based on benzimidazole-pyridine binding units
journal, March 1997

Quantum Dot Bioconjugates for Ultrasensitive Nonisotopic Detection
journal, September 1998

Lifetime- and Color-Tailored Fluorophores in the Micro- to Millisecond Time Regime
journal, February 2000

Thiol-Reactive Luminescent Chelates of Terbium and Europium
journal, March 1999

Crystal structure of the tris 1,2-dimethyl-3-hydroxy-4-pyridinone (DMHP) complex with the Fe(III) ion
journal, June 1992

A Novel Salicylate-Based Macrobicycle with a “Split Personality”
journal, October 1999

Stable 8-Hydroxyquinolinate-Based Podates as Efficient Sensitizers of Lanthanide Near-Infrared Luminescence
journal, December 2005

Spectroscopic properties and design of highly luminescent lanthanide coordination complexes
journal, January 2000

Measurement of photoluminescence quantum yields. Review
journal, April 1971

A Theory of Sensitized Luminescence in Solids
journal, May 1953

Time-resolved detection of lanthanide luminescence for ultrasensitive bioanalytical assays
journal, January 1995

Real-Time DNA Sequencing from Single Polymerase Molecules
journal, January 2009

Optical properties of Cm(III) in crystals and solutions and their application to Cm(III) speciation
journal, April 2006

Equilibrium studies on copper(II)- and iron(III)-monohydroxamates
journal, September 1998

Zwischenmolekulare Energiewanderung und Fluoreszenz
journal, January 1948

Light Harvesting by Phycobilisomes
journal, June 1985

Crescent Oligoamides From Acyclic “Macrocycles” to Folding Nanotubes
journal, October 2001

A Tris-hydroxymethyl-Substituted Derivative of Gd-TREN-Me-3,2-HOPO: An MRI Relaxation Agent with Improved Efficiency
journal, November 2000

Real time quantitative PCR.
journal, October 1996

Development of luminescent lanthanide chelate labels for diagnostic assays
journal, March 1997

Europium as a label in time-resolved immunofluorometric assays
journal, March 1984

LANCE™: Homogeneous Assay Platform for HTS
journal, December 1999

Luminescent lanthanide chelates—a way to more sensitive diagnostic methods
journal, July 1995

Simultaneous Amplification and Detection of Specific DNA Sequences
journal, April 1992

Distance distribution in a dye-linked oligonucleotide determined by time-resolved fluorescence energy transfer
journal, December 1992

Detection of specific polymerase chain reaction product by utilizing the 5'----3' exonuclease activity of Thermus aquaticus DNA polymerase.
journal, August 1991

Solid-Phase Synthesis of Oligonucleotides Labeled with Luminescent Lanthanide(III) Chelates
journal, May 2005

Time Gating Improves Sensitivity in Energy Transfer Assays with Terbium Chelate/Dark Quencher Oligonucleotide Probes
journal, December 2004

  • Johansson, Mary Katherine; Cook, Ronald M.; Xu, Jide
  • Journal of the American Chemical Society, Vol. 126, Issue 50, p. 16451-16455

Stereoselectivity in chiral iron(III) and gallium(III) tris(catecholate) complexes effected by nonbonded weakly polar interactions
journal, July 1993

Total Synthesis of Dimethyl Sulfomycinamate
journal, July 1996

DNA sequencing using a four-color confocal fluorescence capillary array scanner
journal, January 1996

Ultrafast DNA sequencing
journal, December 2003

Molecular Beacons: Spectral Genotyping of Human Alleles
journal, February 1998

Electrochemiluminescent labels for applications in fully aqueous solutions at oxide-covered aluminium electrodes
journal, April 1999

Photoluminescence of thorium(IV) 2-methyl-8-quinolinolate
journal, April 1999

Time-Resolved Fluorescence Imaging of Slab Gels for Lifetime Base-Calling in DNA Sequencing Applications
journal, November 2000

Allelic discrimination by nick-translation PCR with fluorgenic probes
journal, August 1993

New energy transfer dyes for DNA sequencing
journal, July 1997

A photocleavable fluorescent nucleotide for DNA sequencing and analysis
journal, January 2003

Shape-Persistent Aromatic Amide Oligomers: New Tools for Supramolecular Chemistry
journal, December 2006

Multiplex Dye DNA Sequencing in Capillary Gel Electrophoresis by Diode Laser-Based Time-Resolved Fluorescence Detection
journal, November 1998

Genome sequencing in microfabricated high-density picolitre reactors
journal, July 2005

Self-Assembly of CdSe−ZnS Quantum Dot Bioconjugates Using an Engineered Recombinant Protein
journal, December 2000

  • Mattoussi, Hedi; Mauro, J. Matthew; Goldman, Ellen R.
  • Journal of the American Chemical Society, Vol. 122, Issue 49, p. 12142-12150

Electrophoretically Uniform Fluorescent Dyes for Automated DNA Sequencing
journal, March 1996

Emerging technologies in DNA sequencing
journal, December 2005

Syntheses and Properties of Luminescent Lanthanide Chelate Labels and Labeled Haptenic Antigens for Homogeneous Immunoassays
journal, May 1995

Crystal structure of dimeric HIV-1 capsid protein
journal, September 1996

Cymothoe sangaris”:  An Extremely Stable and Highly Luminescent 1,2-Hydroxypyridinonate Chelate of Eu(III)
July 2006

An Octadentate Luminescent Eu(III) 1,2-HOPO Chelate with Potent Aqueous Stability
journal, July 2007

Eu(III) Complexes of Functionalized Octadentate 1-Hydroxypyridin-2-ones: Stability, Bioconjugation, and Luminescence Resonance Energy Transfer Studies
journal, November 2010

Enhanced liquid–liquid anion exchange using macrocyclic anion receptors: effect of receptor structure on sulphate–nitrate exchange selectivity
journal, August 2010

Liposome-mediated gentamicin delivery: development and activity against resistant strains of Pseudomonas aeruginosa isolated from cystic fibrosis patients
journal, February 2005

A closed tube format for amplification and detection of DNA based on energy transfer
journal, June 1997

Characterization of Visible Dyes for Four-Decay Fluorescence Detection in DNA Sequencing
journal, July 1997

Binuclear Metal Complexes. V. Template Synthesis of a Binuclear Copper(II) Complex of a Macrocycle Containing Amido Groups
journal, October 1972

Synthese mehrbasischer Säuren aus Salicylsäure und Kohlensäure
journal, July 1876

Stable Lanthanide Luminescence Agents Highly Emissive in Aqueous Solution: Multidentate 2-Hydroxyisophthalamide Complexes of Sm3+, Eu3+, Tb3+, Dy3+
journal, November 2003

  • Petoud, Stephane; Cohen, Seth M.; Bünzli, Jean-Claude G.
  • Journal of the American Chemical Society, Vol. 125, Issue 44, p. 13324-13325

Synthesis and characterisation of highly emissive and kinetically stable lanthanide complexes suitable for usage ‘in cellulo’
journal, March 2005

A system for rapid DNA sequencing with fluorescent chain-terminating dideoxynucleotides
journal, October 1987

Luminescent Terbium Protein Labels for Time-Resolved Microscopy and Screening
journal, June 2009

Circularly polarized luminescence spectroscopy
journal, February 1986

Design and synthesis of a 3'-O-allyl photocleavable fluorescent nucleotide as a reversible terminator for DNA sequencing by synthesis
journal, April 2005

Luminescent lanthanide complexes as photochemical supramolecular devices
journal, February 1993

Time-resolved fluorescence of a new europium-chelate complex: demonstration of highly sensitive detection of protein and DNA samples
journal, November 1993

Ferric ion sequestering agents. 14. 1-Hydroxy-2(1H)-pyridinone complexes: properties and structure of a novel iron-iron dimer
journal, November 1985

Principles and Biophysical Applications of Lanthanide-Based Probes
journal, June 2002

Four-color DNA sequencing by synthesis on a chip using photocleavable fluorescent nucleotides
journal, April 2005

Fluorescence detection in automated DNA sequence analysis
journal, June 1986

Time-Resolved Fluorescence of Lanthanide Probes and Applications in Biotechnology
journal, January 1987

Selective Inhibition of Fe-versus Cu/Zn-Superoxide Dismutases by 2,3-Dihydroxybenzoic Acid Derivatives
journal, January 2002

Water-Soluble Neutral Calix[4]arene−Lanthanide Complexes: Synthesis and Luminescence Properties
journal, June 1997

Long-Range Nonradiative Transfer of Electronic Excitation Energy in Proteins and Polypeptides
journal, June 1971

Novel 3-hydroxy-2(1H)-pyridinones. Synthesis, iron(III)-chelating properties and biological activity
journal, June 1990

Fluorescence Energy Transfer as a Spectroscopic Ruler
journal, June 1978

6-Carboxamido-5,4-Hydroxypyrimidinones: A New Class of Heterocyclic Ligands and Their Evaluation as Gadolinium Chelating Agents
journal, December 2001

Time-resolved fluorometry: a sensitive method to quantify DNA-hybrids
journal, January 1986

Synthesis of Europium(III) Chelates Suitable for Labeling of Bioactive Molecules
journal, June 1994

The Green Fluorescent Protein
journal, June 1998

Molecular Beacons: Probes that Fluoresce upon Hybridization
journal, March 1996

Multicolor molecular beacons for allele discrimination
journal, January 1998

Stereospecific binding of MRI contrast agents to human serum albumin: the case of Gd-(S)-EOB-DTPA (Eovist) and its (R) isomer
journal, February 2001

Comparative study of fluorescent ternary terbium complexes. Application in enzyme amplified fluorimetric immunoassay for α-fetoprotein
journal, December 1996

Temporally and Spectrally Resolved Imaging Microscopy of Lanthanide Chelates
journal, May 1998

Luminescence and structure of europium compounds
journal, January 2000

Direct genomic fluorescent on-line sequencing and analysis using in vitro amplification of DNA
journal, April 1989

Design and synthesis of new fluorogenic HIV protease substrates based on resonance energy transfer
journal, January 1990

Rapid Sizing of Short Tandem Repeat Alleles Using Capillary Array Electrophoresis and Energy-Transfer Fluorescent Primers
journal, April 1995

Unnatural Amino Acid Mutagenesis of Green Fluorescent Protein
journal, November 2002

Engineering of Highly Luminescent Lanthanide Tags Suitable for Protein Labeling and Time-Resolved Luminescence Imaging
journal, April 2004

  • Weibel, Nicolas; Charbonnière, Loic J.; Guardigli, Massimo
  • Journal of the American Chemical Society, Vol. 126, Issue 15, p. 4888-4896

Detection of PCR products using self-probing amplicons and fluorescence
journal, August 1999

Quantum Yields of Luminescent Lanthanide Chelates and Far-Red Dyes Measured by Resonance Energy Transfer
journal, July 2001

Plutonium(IV) Sequestration: Structural and Thermodynamic Evaluation of the Extraordinarily Stable Cerium(IV) Hydroxypyridinonate Complexes1
journal, September 2000

Selective modification of aspartic acid-101 in lysozyme by carbodiimide reaction
journal, August 1981