IP Library Granted Patent US 7,635,762
Granted Patent B2
US 7,635,762 · App. 10/690,806 · Granted Dec 22, 2009

Luminescent metal ion complexes

Assignee: Biosearch Technologies, Inc.
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Quick Facts
Patent No.
US 7,635,762
App. No.
10/690,806
Granted
Dec 22, 2009
Kind
B2
Abstract

The present invention provides luminescent metal ion complexes for use in a wide range of biological and chemical studies. The luminescent metal ion complexes of the invention comprise a metal ion chelating component covalently bound to a carrier molecule. Also provided are methods of making and using the luminescent metal ion complexes.

Claims (34)

1. A metal ion coordinating component of a luminescent metal ion complex comprising:

(i) a solid support covalently bonded to a non-nucleic acid spacer;

(ii) a nucleobase covalently bonded to said non-nucleic acid spacer, wherein said nucleobase comprises a nitrogenous base;

(iii) a linker covalently bonded to said nitrogenous base, wherein said linker has the formula:

wherein,

R 1 , R 2 , R 3 , and R 4 are individually selected from the group consisting of hydrogen, halogen, —OH, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and OR 5 , wherein

R 5 is selected from hydrogen and substituted or unsubstituted alkyl;

Q 1 and Q 2 are individually selected from the group consisting of a bond, substituted or unsubstituted alkyl, and substituted or unsubstituted heteroalkyl;

x and z are individually selected from the integers 0 to 100; and

y is selected from the integers 1 to 100;

(iv) a metal ion coordinating moiety covalently bonded to said linker to form said metal ion coordinating component.

2. The metal ion coordinating component of claim 1 , wherein said first nucleobase is covalently bonded to an oligonucleotide.

3. The metal ion coordinating component of claim 2 , wherein said oligonucleotide comprises from 1 to 5 additional metal ion coordinating moieties covalently bound to said oligonucleotide.

4. The metal ion coordinating component of claim 1 , wherein said metal ion coordinating moiety is a bidentate metal ion coordinating moiety.

5. The metal ion coordinating component of claim 4 , wherein said bidentate metal ion coordinating moiety is selected from the group consisting of substituted or unsubstituted bipyridyl, substituted or unsubstituted phenanthroline, substituted or unsubstituted 2,4 pentanediene, substituted or unsubstituted hydroxamate, substituted or unsubstituted terpyridine, substituted or unsubstituted dipyridophenazine, and substituted or unsubstituted acetylacetonate.

6. The metal ion coordinating component of claim 4 , wherein said nitrogenous base is selected from the group consisting of guanine, thymine, cytosine, adenine, and uracil.

7. The metal ion coordinating component of claim 4 , wherein said solid support is controlled pore glass.

8. The metal ion coordinating component of claim 4 , wherein said bidentate metal ion coordinating moiety has the formula:

wherein,

R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 are independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl, OR A , NR B R C , NR D OR E , SR F , and SO 2 R G wherein

R 4 and R 5 are optionally joined together with the atoms to which they are attached to form a 3 to 8 membered ring,

R A , R B , R C , R D , R E , R F , and R G are independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl, and

one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 is attached to said linker.

9. The metal ion coordinating component of claim 4 , further comprising a quencher of excited state energy.

10. The metal ion coordinating component of claim 4 , further comprising a metal ion, a second metal ion coordinating component, and a third metal ion coordinating component, wherein said metal ion coordinating component, said second metal ion coordinating component and said third metal ion coordinating component are coordinated to said metal ion to from said luminescent metal ion complex.

11. The metal ion coordinating component of claim 10 , wherein said metal ion coordinating component comprises a first bidentate metal ion coordinating moiety, said second metal ion coordinating component comprises a second bidentate metal ion coordinating moiety, and said third metal ion coordinating component comprises a third bidentate metal ion coordinating moiety.

12. The metal ion coordinating component of claim 10 , wherein said first bidentate metal ion coordinating moiety, said second bidentate metal ion coordinating moiety, and said third bidentate metal ion coordinating moiety are individually selected from the group consisting of substituted or unsubstituted bipyridyl, substituted or unsubstituted phenanthroline, substituted or unsubstituted 2,4 pentanediene, substituted or unsubstituted hydroxamate, substituted or unsubstituted terpyridine, and substituted or unsubstituted acetylacetonate.

13. The metal ion coordinating component of claim 10 , wherein said metal ion is selected from the group consisting of ruthenium, osmium, and rhenium.

14. The metal ion coordinating component of claim 10 , further comprising a quencher of excited state energy.

15. A method of making the metal ion coordinating component of claim 1 , comprising:

(a) covalently bonding said first nucleobase to said linker;

(b) covalently bonding the product of step (a) to said non-nucleic acid spacer;

(c) covalently bonding the product of step (b) to said solid support; and

(d) contacting the product of step (c) with said metal ion coordinating moiety.

Assignments (4)
RELEASE OF SECURITY INTEREST IN PATENTS PREVIOUSLY RECORDED AT REEL/FRAME (035957/0976) Recorded Mar 8, 2016
From: HSBC CORPORATE TRUSTEE COMPANY (UK) LIMITED
To: BIOSEARCH TECHNOLOGIES, INC.
Reel/Frame 038037/0669 →
CORRECTIVE ASSIGNMENT TO CORRECT THE INCORRECT APPL. NO. 61/996,902 PREVIOUSLY RECORDED AT REEL: 035957 FRAME: 0976. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded Aug 11, 2015
From: BIOSEARCH TECHNOLOGIES, INC.
To: HSBC CORPORATE TRUSTEE COMPANY (UK) LIMITED, AS SECURITY AGENT
Reel/Frame 036335/0516 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 30, 2015
From: BIOSEARCH TECHNOLOGIES, INC.
To: HSB CORPORATE TRUST COMPANY (UK) LIMITED, AS SECURITY AGENT
Reel/Frame 035957/0976 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 5, 2004
From: COOK, RONALD M.; LYTTLE, MATT; JOHANSSON, MARY KATHERINE
To: BIOSEARCH TECHNOLOGIES, INC.
Reel/Frame 015196/0418 →
Continuity (2)
Provisional Application 6042048500 · Oct 21, 2002
Related Publication 20040146895A1 · Jul 29, 2004