Lanthanide complexes comprising at least two betaine groups, which can be used as luminescent markers

Patent metadata

Field	Value
Publication number	US-10047106-B2
Application number	US-201414775244-A
Country	US
Kind code	B2
Filing date	Apr 3, 2014
Priority date	Apr 4, 2013
Publication date	Aug 14, 2018
Grant date	Aug 14, 2018

Abstract

The present invention relates to luminescent lanthanide complexes including a chelating agent, formed with a macrocycle or a set of ligands, complexing a lanthanide ion Ln3+, wherein the chelating agent is substituted with at least two groups. The invention is most particularly applied to lanthanide complexes, the chelating agent of which is formed the with three ligands integrating a 2,6 pyridine-di(carboxylic acid) or is formed with a macrocycle having a 1,4,7 triazacyclononane structure.

First claim

The invention claimed is:

1. Lanthanide complexes selected among lanthanide complexes of formula (IV):

wherein:
Ln is a lanthanide, chosen among Eu, Sm, Tb or Dy,
Z represents —C— or —PR 3 —,
R 3 represents a phenyl, benzyl, methyl, ethyl, propyl, n-butyl, sec-butyl, iso-butyl or tert-butyl group,
Chrom1, Chrom2 and Chrom3, either identical or different, are selected from the groups:

wherein:
L 1 represents a direct bond, —C═C— or —C≡C—,
Ar 1 represents an aromatic group selected among phenyl, thiophenyl, furanyl, pyrrolyl, imidazolyl or triazolyl groups, substituted with s R 0 groups, either identical or different,
s is equal to 1, 2 or 3, and
R 0 is selected from:
alkyl groups comprising from 1 to 10 carbon atoms bearing at least one betaine function and/or one reactive function; and
electron donor groups selected from O donors, S donors, NHCO donors, SCO donors, NHCS donors, and SCS donors, said electron donor groups may either bear or not bear one or several betaine groups, and/or a reactive function,

wherein, when all the groups Ar1 represent a phenyl group, at least one of these phenyl groups is substituted with at least one R 0 group including an electron donor group;
wherein at least two of the groups Chrom1, Chrom2 and Chrom3 are substituted with at least one R 0 group bearing at least one betaine group.

2. The lanthanide complexes according to claim 1 , having, at most, 12 betaine groups.

3. The lanthanide complexes according to claim 1 , wherein the at least one reactive function is selected from —COOH, —NH 2 , an acrylamide, an activated amine, an activated ester, an aldehyde, an alkyl halide, an anhydride, an aniline, an azide, an aziridine, a carboxylic acid, a diazoalkane, a haloacetamide, a halotriazine, a hydrazine, an imido ester, an isocyanate, an isothiocyanate, a maleimide, a sulfonyl halide, a thiol, a ketone, an amine, an acid halide, a hydroxysuccinimidyl ester, a succinimidyl ester, a hydroxysulfosuccinimidyl ester, an azidonitrophenyl, an azidophenyl, a 3-(2-pyridyl-dithio)-propionamide, a glyoxal, a triazine, an acetylene group, and groups of formula:

wherein w is an integer belonging to the range from 0 to 8 and v is equal to 0 or 1, and Ar is a saturated or unsaturated heterocycle with 5 or 6 members, comprising from 1 to 3 heteroatoms, optionally substituted with a halogen atom.

4. The lanthanide complexes according to claim 1 , wherein Chrom1, Chrom2 and Chrom3 are defined as follows:
a. either Chrom1, Chrom2 and Chrom3, either identical or different, are selected from the groups:

b. or Chrom1, Chrom2 and Chrom3, either identical or different, are selected from the groups:

with Ar1 which represents a phenyl, thiophenyl, furanyl, pyrrolyl or imidazolyl group substituted with s R 0 groups, either identical or different.

5. The lanthanide complexes according to claim 1 , wherein the substituents R 0 , either identical or different, are selected among:
-L 2 -Alk, -L 2 -L 3 -Q 1 and -L 2 -L 3 -Q 2 ;
the NHCO donor groups selected among: —NHCO(OAlk), —NHCO(NHAlk), —NHCO(NAlk1Alk2), —NHCO(SAlk),
the SCO donor groups selected among: —SCO(OAlk), —SCO(NHAlk), —SCO(NAlk1Alk2), —SCO(SAlk),
the NHCS donor groups selected among: —NHCS(OAlk), —NHCS(NHAlk), —NHCS(NAlk1Alk2), and
the SCS donor groups selected among: —SCS(OAlk), —SCS(NHAlk), —SCS(NAlk1Alk2), —SCS(SAlk),
Alk, Alk1 and Alk2, either identical or different, are alkyl groups comprising from 1 to 10 carbon atoms, optionally substituted with at least one betaine group,
Q 1 represents a betaine group or a branched group bearing at least two betaine groups,
L 2 is a direct bond, —O—, —S—, —NHCO—, —SCO—, —NHCS— or —SCS—,
L 3 is a linker, and
Q 2 is a reactive group able to allow a covalent bonding with a molecule of interest to be marked,
wherein at least two of the present R 0 substituents bear at least one betaine group, so that at least two of the groups Chrom1, Chrom2 and Chrom3 are substituted with at least one R 0 group bearing at least one betaine group.

6. The lanthanide complexes according to claim 1 , wherein Chrom1=Chrom2=Chrom3.

7. The lanthanide complexes according to claim 1 , wherein Chrom1=Chrom2 and are substituted with at least one R 0 group bearing at least one betaine group and Chrom3 is substituted with at least one R 0 group bearing a function -L 2 -L 3 -Q 2 , wherein Q 2 represents a group selected among —COOH, —NH 2 , an acrylamide, an activated amine, an activated ester, an aldehyde, an alkyl halide, an anhydride, an aniline, an azide, an aziridine, a carboxylic acid, a diazoalkane, a haloacetamide, a halotriazine, a hydrazine, an imido ester, an isocyanate, an isothiocyanate, a maleimide, a sulfonyl halide, a thiol, a ketone, an amine, an acid halide, a hydroxysuccinimidyl ester, a succinimidyl ester, a hydroxysulfosuccinimidyl ester, an azidonitrophenyl, an azidophenyl, an 3-(2-pyridyl-dithio)-propionamide, a glyoxal, a triazine, an acetylene group, and the groups of formula:

wherein w is an integer belonging to the range from 0 to 8 and v is equal to 0 or 1, and Ar is a saturated or unsaturated heterocycle with 5 or 6 members, comprising 1 to 3 heteroatoms, optionally substituted with a halogen atom.

8. The lanthanide complexes according to claim 1 , wherein L 1 represents a direct bond or —C≡C—, and the groups Ar1, either identical or different, each represent a phenyl group, substituted with s R 0 groups, either identical or different.

9. The lanthanide complexes according to claim 1 , wherein, in all the groups Ar1, s is equal to 1.

10. The lanthanide complexes according to claim 1 , wherein the groups Ar1, either identical or different, each represent a phenyl group selected from the groups:

11. The lanthanide complexes according to claim 1 , selected among the lanthanide complexes of formula (III):

wherein
Ln is a lanthanide, chosen among Eu, Sm, Tb or Dy,
Chrom4 is selected from the groups:

wherein:
L 1 represents a direct bond, —C═C— or —C≡C—,
Ar2 represents an aromatic group selected among the phenyl, thiophenyl, furanyl, pyrrolyl, imidazolyl or triazolyl groups, said groups Ar2 being substituted with s R 1 groups, either identical or different,
s is equal to 1, 2 or 3, and
R 1 is selected among alkyl groups comprising from 1 to 10 carbon atoms bearing at least one betaine group; and electron donor groups selected from O donors, S donors, NHCO donors, SCO donors, NHCS donors, and SCS donors, said electron donor groups bearing one or several betaine groups,

wherein, when the group Ar2 represents a phenyl group, it is substituted with at least one R 1 group including an electron donor group.

12.

Assignees

• Ecole Normale Superieure Lyon
• Univ Claude Bernard Lyon
• Centre Nat Rech Scient

Inventors

• Maury Olivier
• Andraud Chantal
• Placide Virginie
• Pitrat Delphine

Classifications

• C09K9/02 Primary

  Organic tenebrescent materials · CPC title

• G01N33/582

  with fluorescent label · CPC title

• G01N33/533

  with fluorescent label · CPC title

• C09K2211/182

  of the rare earth metals, i.e. Sc, Y or lanthanide · CPC title

• C09K2211/1029

  containing one nitrogen atom as the heteroatom · CPC title