Ethenyl-substituted dipyrrometheneboron difluoride dyes and their synthesis

• US 5,187,288 A
• Filed: 05/22/1991
• Issued: 02/16/1993
• Est. Priority Date: 05/22/1991
• Status: Expired due to Term

• Current Assignee: Molecular Probes Incorporated (Thermo Fisher Scientific Incorporated)
• Original Assignee: Molecular Probes Incorporated (Thermo Fisher Scientific Incorporated)
• Inventors: Haugland, Richard P., Kang, Hee C.
• Primary Examiner(s): Lee, Mary C.
• Assistant Examiner(s): McKane, Joseph K.
• Application Number:
  US07/704,287
• Time in Patent Office: 636 Days
• Field of Search: 548/110, 548/405
• US Class Current: 548/110
• CPC Class Codes: C07F 5/022 without C-boron linkages
• CPC Class Codes: C09B 57/00 Other synthetic dyes of known constitution
• CPC Class Codes: C09K 11/06 containing organic luminescent materials

Abstract

This invention relates to ethenyl-substituted derivatives of dipyrrometheneboron difluoride dyes that have an absorption maximum at wavelengths longer than about 525 nm, and are electrically neutral, highly photostable and, in most cases, highly fluorescent with relatively narrow absorption and emission spectra. The ethenyl-substituted dyes generally have the structure: ##STR1## wherein at least one of the fluorophore substituents R₁ -R₇, is an ethenyl group of the formula --CX_m ═CY_m --Z_m, where m is any combination of locations 1, 2, 3, 4, 5, 6, and 7 corresponding to the location of parent fluorophore substituents R_1-7. The initial ethenyl substituents X_m, Y_m, and Z_m, which may be the same or different, are halogen, alkyl (containing 1-10 carbon atoms), cyano, ester, amide, ethenyl or polyethenyl, aryl or heteroaryl. The non-ethenyl substituents, which may be the same or different, are hydrogen, halogen, alkyl (containing 1-18 carbon atoms), aryl, arylalkyl, heteroaryl, acyl or sulfo.

Claims

1. A compound of the general formula:

##STR22## wherein at least one of the fluorophore substituents R₁ -R₇ is an initial ethenyl group having initial ethenyl substituents;

or a conjugated dienyl group having initial and secondary ethenyl substituents;

or a conjugated trienyl group having initial, secondary and tertiary ethenyl substituents, and

where said initial, secondary, and tertiary ethenyl substituents which may be the same or different, are hydrogen;

halogen;

alkyl (containing 1-10 carbon atoms);

cyano;

carboxylate ester;

carboxamide;

or aryl or heteroaryl, where said heteroaryl is pyrrole, thiophene, furan, oxazole, isoxazole, oxadiazole, imidazole, benzoxazole, benzothiazole, benzimidazole, benzofuran, or indole, which aryl or heteroaryl may be further substituted, one or more times, by alkyl (containing 1-5 carbon atoms), or alkoxy groups the alkyl portions of which groups have less than 5 carbon atoms, or combinations thereof; and

the remaining fluorophore substituents R₁ -R₇ that are non-ethenyl, -dienyl, or -trienyl, which may be the same or different, are hydrogen;

alkyl (containing 1-18 carbon atoms);

acyl;

sulfo;

arylalkyl, the alkyl portion of which contains 1-18 carbon atoms;

or aryl or heteroaryl, which may be further substituted, one or more times, by alkyl (containing 1-5 carbon atoms), or alkoxy or dialkylamino groups wherein the alkyl portions of such groups have less than 5 carbon atoms, or combinations thereof;

said compound having an absorption maximum at a wavelength longer than about 525 nm.

2. A compound, as claimed in claim 1, where there is one initial ethenyl group of the formula--CX═

CY--Z, located at R₁, R₂, R₃, or R₄ ;

at least one of the corresponding initial ethenyl substituents X, Y, or Z, which may be the same or different, is hydrogen;

at least one other of the corresponding initial ethenyl substituents is hydrogen;

halogen;

alkyl (containing 1-10 carbon atoms);

cyano;

carboxylate ester;

carboxamide;

or aryl or heteroaryl, which may be further substituted, one or more times; and

the remaining six non-ethenyl fluorophore substituents at R_1-7, which may be the same or different, are hydrogen;

alkyl (containing 1-5carbon atoms);

aryl;

heteroaryl;

or aryl or heteroaryl that is further substituted, one or more times.

3. A compound, as claimed in claim 2, where the initial ethenyl group is located at R₁, R₂, or R₃ ;

and

at least one of the corresponding initial ethenyl substituents is aryl or heteroaryl;

or aryl or heteroaryl that is further substituted, one or more times.

4. A compound, as claimed in claim 3, where the initial ethenyl substituent Z is heteroaryl which heteroaryl may be further substituted, one or more times.

5. A compound, as claimed in claim 3, where the initial ethenyl substituent Z is aryl that is phenyl;

1-napthyl;

2-naphthyl;

1-pyrenyl;

or 9-anthryl;

which aryl may be further substituted, one or more times.

6. A compound, as claimed in claim 2, where the initial ethenyl group is located at R₄ and X, Y, or Z is aryl or heteroaryl;

or aryl or heteroaryl that is further substituted one or more times.

7. A compound, as claimed in claim 6, where the initial ethenyl substituent Z is aryl that is phenyl;

1-naphthyl;

2-naphthyl;

1-pyrenyl;

or 9-anthryl;

which aryl may be further substituted, one or more times.

8. A compound, as claimed in claim 6, where the initial ethenyl substituent Z is heteroaryl;

which heteroaryl may be further substituted, one or more times.

9. A compound, as claimed in claim 1, where there are two initial ethenyl groups symmetrically located at R₁ and R₇, R₂ and R₆, or R₃ and R₅, each having the formula --CX═

CY--Z;

at least one of the three corresponding initial ethenyl substituents X, Y and Z from each symmetrical ethenyl group, which may be the same or different, is hydrogen; and

at least one other of the three corresponding initial ethenyl substituents from each symmetrical ethenyl group, which may be the same or different, is hydrogen;

halogen;

alkyl (containing 1-10 carbon atoms);

cyano;

carboxylate ester;

carboxamide;

or aryl or heteroaryl, which may be further substituted, one or more times; and

the remaining five non-ethenyl fluorophore substituents at R_1-7, which may be the same or different, are hydrogen;

alkyl (containing 1-5 carbon atoms);

aryl;

heteroaryl;

or aryl or heteroaryl that is further substituted, one or more times.

10. A compound, as claimed in claim 9, where at least one of the six corresponding initial ethenyl substituents, which may be the same or different, is aryl or heteroaryl;

or aryl or heteroaryl that is further substituted, one or more times.

11. A compound, as claimed in claim 10, where at least two of the six corresponding initial ethenyl substituents, which may be the same or different, are aryl or heteroaryl;

or aryl or heteroaryl that is further substituted, one or more times.

12. A compound, as claimed in claim 11, where the corresponding initial ethenyl substituents Z, from each of the symmetrically located initial ethenyl groups, are each heteroaryl, which may be the same or different, which heteroaryl may be further substituted, one or more times.

13. A compound, as claimed in claim 11, where the initial ethenyl substituents Z, from each of the symmetrically located initial ethenyl groups, are each aryl, which may be the same or different, where each aryl is phenyl;

1-naphthyl;

2-naphthyl;

1-pyrenyl;

or 9-anthryl;

which aryl may be further substituted, one or more times.

14. A compound, as claimed in claim 11, where each initial ethenyl substituent that is aryl, which may be the same or different, is phenyl;

1-naphthyl;

2-naphthyl;

1-pyrenyl;

or 9-anthryl;

which aryl may be further substituted, one or more times.

15. A compound, as claimed in claim 1, where there is one conjugated dienyl group having initial and secondary ethenyl substituents;

or conjugated trienyl group having initial, secondary and tertiary ethenyl substituents located at R₁, R₂, R₃, or R₄ ;

at least one of the corresponding initial ethenyl substituents is hydrogen; and

at least one of the corresponding secondary ethenyl substituents is hydrogen.

16. A compound, as claimed in claim 15, where the conjugated dienyl or trienyl group has the formula:

--CX═

CY--(CH═

CH)_n --Z, where n=0 or 1;

the secondary or tertiary ethenyl substituent Z is aryl;

heteroaryl;

or aryl or heteroaryl that is further substituted, one or more times; and

the remaining six non-dienyl or -trienyl fluorophore substituents at R_1-7 are hydrogen;

alkyl (containing 1-5 carbon atoms);

aryl;

heteroaryl;

or aryl or heteroaryl that is further substituted, one or more times.

17. A compound, as claimed in claim 1, where there are two conjugated dienyl or trienyl groups symmetrically substituted at R₁ and R₇, R₂ and R₆, or R₃ and R₅ ;

at least one of the three corresponding initial ethenyl substituents from each symmetrical dienyl or trienyl group, which may be the same or different, is hydrogen; and

at least one of the corresponding secondary ethenyl substituents from each symmetrical group, which may be the same or different, is hydrogen.

18. A compound, as claimed in claim 17, where each of the symmetrically located conjugated dienyl or trienyl groups, which may be the same or different, has the formula:

--CX═

CY--(CH═

CH)_n --Z, where n=0 or 1;

the corresponding secondary or tertiary ethenyl substituents Z, which may be the same or different, are aryl;

heteroaryl;

or aryl or heteroaryl that is further substituted, one or more times; and

the remaining five non-ethenyl fluorophore substituents at R_1-7 are hydrogen;

alkyl (containing 1-5 carbon atoms);

or aryl or heteroaryl, which may be further substituted, one or more times.

19. A compound, as claimed in claim 18, where each substituent that is aryl, which may be the same or different, is phenyl;

1-naphthyl;

2-naphthyl;

1-pyrenyl;

or 9-anthryl;

which aryl may be further substituted, one or more times.

20. A compound of the general formula:

##STR23## wherein one or two of the fluorophore substituents R₁ -R₇ is an initial ethenyl or conjugated dienyl or trienyl group of the formula --(CH═

CH)_n --Z, where n is 1, 2, or 3, where one or two of the corresponding initial, secondary, or tertiary ethenyl substituents Z, which may be the same or different, are hydrogen;

halogen;

alkyl (containing 1-10 carbon atoms);

cyano;

carboxylate ester;

carboxamide;

or aryl that is phenyl, 1-naphthyl, 2-naphthyl, 1-pyrenyl, or 9-anthryl;

or heteroaryl that is pyrrole, thiophene, furan, oxazole, isoxazole, oxadiazole, imidazole, benzoxazole, benzothiazole, benzimidazole, benzofuran, or indole;

which aryl or heteroaryl may be further substituted, one or more times, by alkyl (containing 1-5 carbon atoms), or alkoxy groups the alkyl portions of which groups have less than 5 carbon atoms, or combinations thereof and

the remaining five or six fluorophore substituents R₁ -R₇ that are non-ethenyl, dienyl, or trienyl, which may be the same or different, are hydrogen;

halogen;

alkyl (containing 1-18 carbon atoms);

acyl;

sulfo;

arylalkyl, the alkyl portion of which contains 1-18 carbon atoms;

or aryl that is phenyl, 1-naphthyl, 2-naphthyl, 1-pyrenyl, or 9-anthryl;

or heteroaryl that is pyrrole, thiophene, furan, oxazole, isoxazole, oxadiazole, imidazole, benzoxazole, benzothiazole, benzimidazole, benzofuran, or indole;

which aryl or heteroaryl may be further substituted, one or more times, by alkyl (containing 1-5 carbon atoms), or alkoxy or dialkylamino groups wherein the alkyl portions of such groups have less than 5 carbon atoms, or combinations thereof;

said compound having an absorption maximum at a wavelength longer than about 530 nm and an emission maximum at a wavelength longer than about 550.