James L Whitaker

US Patent:

52274870, Jul 13, 1993

Filed:

Apr 16, 1990

Appl. No.:

7/509360

Inventors:

Richard P. Haugland - Eugene OR
James E. Whitaker - Eugene OR

Assignee:

Molecular Probes, Inc. - Eugene OR

International Classification:

C07D22120
C07D491052
C07D41314

US Classification:

546 15

Abstract:

Novel fluorescent dyes based on the rhodol structure are provided. The new reagents contain functional groups capable of forming a stable fluorescent product with functional groups typically found in biomolecules or polymers including amines, phenols, thiols, acids, aldehydes and ketones. Reactive groups in the rhodol dyes include activated esters, isothiocyanates, amines, hydrazines, halides, acids, azides, maleimides, aldehydes, alcohols, acrylamides and haloacetamides. The products are detected by their absorbance or fluorescence properties. The spectral properties of the fluorescent dyes are sufficiently similar in wavelengths and intensity to fluorescein or rhodamine derivatives as to permit use of the same equipment. The dyes, however, show less spectral sensitivity to pH in the physiological range than does fluorescein, have higher solubility in non-polar solvents and have improved photostability and quantum yields.

US Patent:

51324326, Jul 21, 1992

Filed:

Sep 22, 1989

Appl. No.:

7/410837

Inventors:

Richard P. Haugland - Eugene OR
James E. Whitaker - Eugene OR

Assignee:

Molecular Probes, Inc. - Eugene OR

International Classification:

C07C24724
C07C30938
C01D20736
G01N 2200

US Classification:

548518

Abstract:

The invention relates to novel fluorescent dyes based on the following pyrenyloxy sulfonic acid structure: ##STR1## wherein at least one of R. sub. 1, R. sub. 2, R. sub. 3, and R. sub. 4 is --OCH. sub. 2 C(O)OCH. sub. 3, --OCH. sub. 2 CON(O)H, --OCH. sub. 2 CON. sub. 3, --OCH. sub. 2 CONHNH. sub. 2, ##STR2## or --CH. sub. 2 CONH(CH. sub. 2). sub. n NH. sub. 2 where n is an integer from 1 to 10; at least one of R. sub. 1, R. sub. 2, R. sub. 3, and R. sub. 4 is sulfonic acid or alkali salts of sulfonic acid; and all other of R. sub. 1, R. sub. 2, R. sub. 3, and R. sub. 4 are hydrogen or a hydroxyl group. The new reagents contain functional groups typically found in biomolecules or polymers. The spectral properties of the fluorescent dyes are sufficiently different in wavelengths and intensity from fluorescein as to permit simultaneous use of both dyes with minimum interference. The dyes have narrower spectral band-widths and smaller Stokes' shifts than other reactive dyes with similar spectral properties, do not show appreciable sensitivity to pH, have higher solubilities in aqueous solvents and have good quantum yields and photostability.

US Patent:

49451715, Jul 31, 1990

Filed:

Aug 10, 1987

Appl. No.:

7/083459

Inventors:

Richard P. Haugland - Junction City OR
James Whitaker - Eugene OR

Assignee:

Molecular Probes, Inc. - Eugene OR

International Classification:

C07D31178

US Classification:

549224

Abstract:

Synthesis and applications of fluorescent dyes which are derivatives of benzo[c]xanthenes is described. The dyes exhibit pH dependent absorption and fluorescence spectra with pKas near the normal physiological range. Unlike fluorescein, the dyes exhibit emission of different characteristic wavelengths dependent on the pH of the medium. This permits several methods of measuring the pH of the medium in contact with the indicator including measuring two emissions with one excitation, selectively exiting the acid and base forms independently and measuring their emission at either single or dual wavelengths, or measuring the characteristic pH dependent absorption or fluorescence excitation spectral. Methods are presented for making the indicators permeant to cell membranes for the measurement of intracellular pH.

US Patent:

54420458, Aug 15, 1995

Filed:

Mar 8, 1993

Appl. No.:

8/028319

Inventors:

Richard P. Haugland - Eugene OR
James E. Whitaker - Eugene OR

Assignee:

Molecular Probes, Inc. - Eugene OR

International Classification:

G01N 3700
C07K 113
C07D21100

US Classification:

5303913

Abstract:

Novel fluorescent dyes based on the rhodol structure are provided. The new reagents contain functional groups capable of forming a stable fluorescent product with functional groups typically found in biomolecules or polymers including amines, phenols, thiols, acids, aldehydes and ketones. Reactive groups in the rhodol dyes include activated esters, isothiocyanates, amines, hydrazines, halides, acids, azides, maleimides, aldehydes, alcohols, acrylamides and haloacetamides. The products are detected by their absorbance or fluorescence properties. The spectral properties of the fluorescent dyes are sufficiently similar in wavelengths and intensity to fluorescein or rhodamine derivatives as to permit use of the same equipment. The dyes, however, show less spectral sensitivity to pH in the physiological range than does fluorescein, have higher solubility in non-polar solvents and have improved photostability and quantum yields.