Lanthanide clusters and methods of use thereof

Patent metadata

Field	Value
Publication number	US-2016002269-A1
Application number	US-201414766996-A
Country	US
Kind code	A1
Filing date	Feb 13, 2014
Priority date	Feb 11, 2013
Publication date	Jan 7, 2016
Grant date	—

Abstract

The present invention is directed to multinuclear lanthanides chiral clusters, based on phenyl-oxazoline-amide (POxA) ligands, and to methods of use thereof. The chiral clusters of this invention are highly fluorescent with high stability.

First claim

1 . A multinuclear lanthanide chiral cluster comprising phenyl-oxazoline-amide (POxA) ligand or salt thereof represented by the structure of formula IA:

and lanthanide(III) ions;
wherein,
R 1 is hydrogen, alkyl, alkenyl, alkyldiazo, aryldiazo, alkynyl, aryl, halogen, —C≡C-Ph-R, —N═N-Ph-R, CN, NH 2 , OH, N 3 , NO 2 , COON, COOR, SO 3 H, SO 3 R, SO 2 NHR, O-alkyl, alkylamino, haloalkyl, or R 1 and R 2 combine together to form a 5-7 membered ring; wherein said 5-7 membered ring is saturated or unsaturated cycloalkyl or heterocycle; wherein said alkyl, alkenyl, alkyldiazo, aryldiazo, alkynyl, aryl and saturated or unsaturated cycloalkyl or heterocycle is substituted or unsubstituted;
R 2 is hydrogen, alkyl, alkenyl, alkyldiazo, aryldiazo, alkynyl, aryl, halogen, CN, NH 2 , OH, N 3 , NO 2 , COOH, COOR, SO 3 H, SO 3 R, SO 2 NHR, O-alkyl, alkylamino, haloalkyl, or R 1 and R 2 combine together to form a 5-7 membered ring; wherein said 5-7 membered ring is saturated or unsatureated cycloalkyl or heterocycle; wherein said alkyl, alkenyl, alkyldiazo, aryldiazo, alkynyl aryl, and saturated or unsaturated cycloalkyl or heterocycle is substituted or unsubstituted;
R 3 is alkyl, aryl, alkenyl, alkyldiazo, aryldiazo, alkynyl, halogen, CN, NH 2 , OH, N 3 , NO 2 , COOH, SO 3 H, SO 3 R, SO 2 NHR, COOR, O-alkyl, alkylamino or haloalkyl; wherein said alkyl, alkenyl, alkyldiazo, aryldiazo, alkynyl and aryl is substituted or unsubstituted;
R 4 is alkyl, alkenyl, alkyldiazo, aryldiazo, alkynyl, polyethylene glycol (PEG), sugars, glucose, manse, proteins, antibody, peptide, —CHR′COR, saturated or unsaturated cycloalkyl or heterocycle, or R 4 and R 5 combine together with the nitrogen to form a 5-7 membered ring; wherein said 5-7 membered ring is saturated or unsaturated cycloalkyl or heterocycle; wherein said alkyl, alkenyl, alkyldiazo, aryldiazo, alkynyl and saturated or unsaturated cycloalkyl or heterocycle is substituted or unsubstituted;
R 5 is hydrogen, alkyl, alkenyl or alkynyl, or R 3 and R 4 combine together with the nitrogen to form a 5-7 membered ring; wherein said 5-7 membered ring is saturated or unsaturated cycloalkyl or heterocycle;
R is hydrogen, alkyl, alkylamine, OH—N(Alkyl) 2 , alkenyl, alkynyl or saturated or unsaturated cycloalkyl or heterocycle; wherein said alkyl, alkenyl, alkynyl and saturated or unsaturated cycloalkyl or heterocycle is substituted or unsubstituted; and
R′ is an amino acid side chain.

2 . The chiral structure of claim 1 , wherein R 1 is H, halogen, —C≡C, SO 3 H, SO 3 Na, NH 2 or NO 2 .

3 . The chiral cluster of claim 1 , wherein R 3 is an alkyl.

4 . The chiral cluster of claim 1 . wherein R 4 is an alkyl or saturated or unsaturated cycloalkyl or heterocycle.

5 . (canceled)

6 . The chiral structure of claim 1 , wherein R 5 is hydrogen.

7 . The chiral cluster of claim 1 , wherein a three lanthanide cluster comprises three lanthanides which coordinate to said POxA ligand as presented by the structure of formula Ila and the structure of formula IIb in equal ratios:

wherein,
Ln is a lanthanide(III) ion;
oxygen bridges coordinate between said lanthanide ions; and said cluster further comprises one or more oxygen based ligands, one or more halogens, or combination thereof.

8 . The chiral cluster of claim 1 , wherein a seven lanthanide cluster comprises seven lanthanides which coordinate to said POxA ligand as presented by the structure of formula IIa, IIb and IIc in equal ratios:

wherein,
Ln is a lanthanide(III) ion:
oxygen bridges coordinate between said lanthanide ions: and said cluster further comprises one or more oxygen based ligands, one or more halogens, or combination thereof.

9 . The chiral cluster of claim 7 , wherein said oxygen based ligand is alcohol or water.

10 . The chiral cluster of claim 1 , wherein said lanthanide is La(III), Pr(III), Pm(III), Sm(III), Eu(III), Gd(III), Tb(III), Dy(III), Ho(III), Er(III), Yb(III) or Lu(III).

11 . The chiral cluster of claim 1 , wherein said lanthanide is the same or different.

12 . The chiral cluster of claim 1 , wherein said phenyl-oxazoline-amide (POxA) ligand is a cis isomer with 4R,5R or 4S,5S chiral centers and said cluster is a three lanthanides cluster with six phenyl-oxazoline-amide (POxA) ligands.

13 . The chiral cluster of claim 1 , wherein said phenyl-oxazoline-amide (POxA) ligand is a trans isomer with 4R,5S or 4S, 5R chiral centers and said cluster is a seven lanthanides cluster with nine phenyl-oxazoline-amide (POxA) ligands.

14 . (canceled)

15 . (canceled)

16 . The chiral cluster of claim 1 , wherein said cluster further comprises oxygen bridges between the lanthanides.

17 . The chiral cluster of claim 1 , wherein said cluster is emitting circularly polarized luminescence (CPL).

18 . A crystalline structure of said chiral cluster of claim 7 , wherein said three lanthanide cluster is represented by the structures of FIGS. 2B , 2 C, 3 A, 3 B, 4 A, 4 B, 5 A or 5 B.

19 . A crystalline structure of said chiral cluster of claim 8 , wherein said seven lanthanide cluster is represented by the structures of FIG. 2A .

20 . A multinuclear lanthanide chiral cluster comprising phenyl-oxazoline-amide (POxA) ligand or salt thereof represented by the structure of formula IIIA:

and lanthanide (III) ions;
wherein,
Q is a sensor, monomeric building-block for polymerization, a polymer, chromophore, surface adhesive group or combination thereof;
L is a bond or a linker;
R 2 is hydrogen, alkyl, alkenyl, alkyldiazo, aryldiazo, alkynyl, aryl, halogen, —C≡C-Ph-R, —N═N-Ph-R, CN, NH 2 , OH, N 3 , NO 2 , COOH, COOR, SO 3 H, SO 3 R, SO 2 NHR, O-alkyl, alkylamino, haloalkyl, or R 1 and R 2 combine together to form a 5-7 membered ring; wherein said 5-7 membered ring is saturated or unsatureated cycloalkyl or heterocycle; wherein said alkyl, alkenyl, alkyldiazo, aryldiazo, alkynyl, aryl and saturated or unsaturated cycloalkyl or heterocycle is substituted or unsubstituted;
R 3 is alkyl, aryl, alkenyl, alkyldiazo, aryldiazo, alkynyl, halogen, CN, NH 2 , OH, N 3 , NO 2 , COOH, SO 3 H, SO 3 R, SO 2 NHR, COOR, O-alkyl, alkylamino or haloalkyl; wherein said alkyl, alkenyl, alkyldiazo, aryldiazo, alkynyl and aryl is substituted or unsubstituted;
R4 is alkyl, alkenyl, alkyldiazo, aryldiazo, alkynyl, polyethylene glycol (PEG), sugars, glucose, manse, galactose, proteins, antibody, peptide, -CHR′COR, saturated or unsaturated cycloalkyl or heterocycle; or R 4 and R 5 combine together with the nitrogen to form a 5-7 membered ring; wherein said 5-7 membered ring is saturated or unsaturated cycloalkyl or heterocycle; wherein said alkyl, alkenyl, alkyldiazo, aryldiazo, alkynyl and saturated or unsaturated cycloalkyl or heterocycle is substituted or unsubstituted;
R 5 is hydrogen, alkyl, alkenyl or alkynyl or R 5 and R 4 combine together with the nitrogen to form a 5-7 membered ring; wherein said 5-7 membered ring is saturated or unsaturated cycloalkyl;
R is hydrogen, alkyl, alkylamine, OH, —N(Alkyl) 2 , alkenyl, alkynyl or saturated or unsaturated cycloalkyl or heterocycle

Assignees

• Yeda Res & Dev

Inventors

• Shanzer Abraham
• Melman Galina
• Barda Yaniv
• Kikkeri Raghavendra
• Kraiz Boris
• Ginat Larissa

Classifications

• C09D11/38

  characterised by non-macromolecular additives other than solvents, pigments or dyes · CPC title

• C09K2211/182

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

• C09K11/06

  containing organic luminescent materials · CPC title

• A61K49/106

  the complex-forming compound being cyclic, e.g. DOTA · CPC title

• C07F5/003 Primary

  without C-Metal linkages · CPC title