Fluorescein-based metal sensors

• US 7,615,377 B2
• Filed: 08/27/2004
• Issued: 11/10/2009
• Est. Priority Date: 09/05/2003
• Status: Active Grant

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Nolan, Elizabeth Marie, Lippard, Stephen J.
• Primary Examiner(s): Warden; Jill
• Assistant Examiner(s): HYUN, PAUL SANG HWA
• Application Number:
  US10/928,924
• Publication Number:
  US 20050112769A1
• Time in Patent Office: 1,901 Days
• Field of Search: 544/1, 544/36, 544/58.1, 544/101, 544/102, 544/344, 546/102, 435/6, 436/73, 436/7, 436/172, 436/76, 436/77, 436 79- 84, 436/166, 436/173, 540/1, 549/26, 549/228, 549/265, 549223-226, 562/466, 422/55, 422/82.08
• US Class Current: 436/166
• CPC Class Codes: G01N 31/22 using chemical indicators G01N31/02 takes precedence
• CPC Class Codes: G01N 33/5308 for analytes not provided for elsewhere, e.g. nucleic acids, uric acid, worms, mites
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

The present invention is directed, in part, to fluorescein-based ligands for detection of metal ions, and methods of making and using the same.

Claims

1. A fluorescein-based ligand, comprising a ligand having any one of the following structures:

2. The fluorescein-based ligand of claim 1, wherein upon addition of about 500 nM of said ligand to an aqueous solution containing Hg²⁺ at about 2 ppb and at about pH 7.0, the fluorescence of the fluorescein-based ligand increases by at least about 5%.

3. The fluorescein-based ligand of claim 2, wherein upon addition of about 500 nM of said ligand to an aqueous solution containing Hg²⁺ at about 2 ppb and at about pH 7.0, the fluorescence of the fluorescein-based ligand increases by at least about 10%.

4. The fluorescein-based ligand of claim 3, wherein upon addition of about 500 nM of said ligand to an aqueous solution containing Hg²⁺ at about 2 ppb and at about pH 7.0, the fluorescence of the fluorescein-based ligand increases by at least about 50%.

5. The fluorescein-based ligand of claim 4, wherein upon addition of about 500 nM of said ligand to an aqueous solution containing Hg²⁺ at about 2 ppb and at about pH 7.0, the fluorescence of the fluorescein-based ligand increases by at least about 100%.

6. The fluorescein-based ligand of claim 1, wherein upon addition of about 1 μ

M of said ligand to an aqueous solution containing Hg²⁺ at about 1 ppm and at about pH 7.0, the fluorescence of the fluorescein-based ligand increases by at least about 5%.

7. The fluorescein-based ligand of claim 1, wherein upon addition of about 1 μ

M of said ligand to an aqueous solution containing Hg²⁺ at about 10 ppm and at about pH 7.0, the fluorescence of the fluorescein-based ligand increases by at least about 5%.

8. The fluorescein-based ligand of claim 1, wherein the fluorescein structure of said ligand has one or more K substituents at any of the aromatic ring carbon positions.

9. The fluorescein-based ligand of claim 1, wherein said ligand forms a chelating agent upon complexation of said ligand with a metal ion.

10. The fluorescein-based ligand of claim 1, wherein said ligand forms a bidentate or tridentate chelating agent upon said complexation.

11. A coordination complex, comprising a metal ion coordinated to one of the fluorescein-based ligands claimed above.

12. The coordination complex of claim 11, wherein said metal ion is a heavy metal ion.

13. The coordination complex of claim 11, comprising Hg²⁺ coordinated to one of the fluorescein-based ligands claimed above.