US5453505A
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US
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N-heteroaromatic ion and iminium ion substituted cyanine dyes for use as fluorescence labels
Assignee: Biometric Imaging Inc
•
Filing: 1994-06-30
•
Granted: 1995-09-26
•
Expires: 2014-06-30
Abstract
Abstract The present invention relates to iminium ion substituted cyanine dyes having a fluoresence absorbance of between about 500 and 900 nm, a reduced tendency to aggregate and enhanced photostability. The cyanine dyes of the present invention are represented by the formula ##STR1## wherein n is 0, 1, 2 or 3; m is 0, 1, 2 or 3; R 1 and R 2 are taken together to form an aromatic ring or a fused polycyclic aromatic ring; R 3 and R 4 are taken together to form an aromatic ring or a fused polycyclic aromatic ring; R 5 and R 6 are independently selected from the group consisting of (CH 2 ) p X where p is 1-18 and X is a functional group that reacts with amino, hydroxyl and sulfhydryl nucleophiles; R 7 and R 8 are independently selected from the group consisting of hydrogen, C1-C10 alkyl groups and where R 7 and R 8 are taken together to form a five- or six- membered heterocyclic ring; R 9 are each independently selected from the group consisting of hydrogen, alkyl and where more than one R 9 are taken together to form a five- or six- membered ring; Y is selected from the group consisting of C(CH 3 ) 2 , S, O and Se; and Z is selected from the group consisting of C(CH 3 ) 2 , S, O and Se.
Inventors
- 👤 Linda G. Lee
- 👤 Sam L. Woo
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-02 01:35
CPC Classifications
A; A61; A61K; A61K49/00; A61K49/001; A61K49/0013; A61K49/0017; A61K49/0019; A61K49/0021; A61K49/0032; C; C09; C09B; C09B23/00; C09B23/0008; C09B23/0041; C09B23/0066; C09B23/02; G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/53; G01N33/531; G01N33/532; G01N33/533; Y; Y10; Y10S; Y10S435/00; Y10S435/968; Y10S436/00; Y10S436/80; Y10S530/00; Y10S530/802
Claims Analysis
Total Claims: 42
Claim 1
Independent Claim
190 words
A cyanine dye having the formula ##STR27## wherein n and m are each independently either 0, 1, 2 or 3; R 1 and R 2 are taken together to form an aromatic ring or a fused polycyclic aromatic ring; R 3 and R 4 are taken together to form an aromatic ring or a fused polycyclic aromatic ring; R 5 and R 6 are independently selected from the group consisting of (CH 2 ) p X where p is 1-18 and X is a functional group that reacts with amino, hydroxy or sulfhydryl nucleophiles; R 7 and R 8 are independently selected from the group consisting of hydrogen, C1-C10 alkyl groups and where R 7 and R 8 are taken together to form a five- or six- membered heterocyclic ring; R 9 are each independently selected from the group consisting of hydrogen, alkyl and where more than one R 9 are taken together to form a five- or six- membered ring; Y is selected from the group consisting of C(CH 3 ) 2 and S; and Z is selected from the group consisting of C(CH 3 ) 2 and S.
Claim 2
Dependent Claim
190 words
A cyanine dye having the formula ##STR27## wherein n and m are each independently either 0, 1, 2 or 3; R 1 and R 2 are taken together to form an aromatic ring or a fused polycyclic aromatic ring; R 3 and R 4 are taken together to form an aromatic ring or a fused polycyclic aromatic ring; R 5 and R 6 are independently selected from the group consisting of (CH 2 ) p X where p is 1-18 and X is a functional group that reacts with amino, hydroxy or sulfhydryl nucleophiles; R 7 and R 8 are independently selected from the group consisting of hydrogen, C1-C10 alkyl groups and where R 7 and R 8 are taken together to form a five- or six- membered heterocyclic ring; R 9 are each independently selected from the group consisting of hydrogen, alkyl and where more than one R 9 are taken together to form a five- or six- membered ring; Y is selected from the group consisting of C(CH 3 ) 2 and S; and Z is selected from the group consisting of C(CH 3 ) 2 and S.
Claim 3
Dependent Claim
37 words
A cyanine dye according to claim 1 wherein R 7 and R 8 are taken together to form a ring selected from the group consisting of pyridinium, imidazolium, pyrrolium, pyrazolium, pyrazinium, pyrimidinium, pyridazinium, purinium, quinolinium and isoquinolinium.
Claim 4
Dependent Claim
23 words
A cyanine dye according to claim 2 wherein R 7 and R 8 are taken together to form a pyridinium or imidazolium ring.
Claim 5
Dependent Claim
33 words
A cyanine dye according to claim 3 wherein R 7 and R 8 are taken together to form a substituent selected from the group consisting of: a 4-dimethylaminopyridinium, 4-(4-morpholinyl)-pyridinium, and a 1-methylimidazolium substitutent.
Claim 6
Dependent Claim
57 words
A cyanine dye according to claim 1 where X is independently selected from the group consisting of carboxylic acids, acid halides, sulfonic acids, esters, aldehydes, disulfides, isothiocyanates, isocyanates, monochlorotriazine, dichlorotriazine, mono- or di-halogen substituted pyridines, mono- or di-halogen substituted diazines, maleimide, aziridines, sulfonyl halides, hydroxysuccinimide esters, hydroxysulfosuccinimide esters, imido esters, hydrazines, azidonitrophenyl, azides, 3-(2-pyridyl dithio)propionamide and glyoxal.
Claim 7
Dependent Claim
13 words
A cyanine dye according to claim 5 where X is a carboxylic acid.
Claim 8
Dependent Claim
37 words
A cyanine dye according to claim 5 wherein R 7 and R 8 are taken together to form a ring selected from the group consisting of pyridinium, imidazolium, pyrrolium, pyrazolium, pyrazinium, pyrimidinium, pyridazinium, purinium, quinolinium and isoquinolinium.
Claim 9
Dependent Claim
16 words
A cyanine dye according to claim 1 wherein (n+m) is less than or equal to 3.
Claim 10
Dependent Claim
11 words
A cyanine dye according to claim 8 wherein n=1 and m=1.
Claim 11
Dependent Claim
18 words
A cyanine dye according to claim 1 wherein Y and Z each are C(CH 3 ) 2 .
Claim 12
Dependent Claim
152 words
A cyanine dye having the formula ##STR28## wherein r is 1, 2 or 3; R 1 and R 2 are taken together to form an aromatic ring or a fused polycyclic aromatic ring; R 3 and R 4 are taken together to form an aromatic ring or a fused polycyclic aromatic ring; R 5 and R 6 are independently selected from the group consisting of (CH 2 ) p X where p is 1-18 and X is a functional group that reacts with amino, hydroxy or sulfhydryl nucleophiles; R 7 and R 8 are independently selected from the group consisting of hydrogen, C1-C10 alkyl and where R 7 and R 8 are taken together to form a five- or six- membered heterocyclic ring; Y is selected from the group consisting of C(CH 3 ) 2 and S; and Z is selected from the group consisting of C(CH 3 ) 2 and S.
Claim 13
Dependent Claim
152 words
A cyanine dye having the formula ##STR28## wherein r is 1, 2 or 3; R 1 and R 2 are taken together to form an aromatic ring or a fused polycyclic aromatic ring; R 3 and R 4 are taken together to form an aromatic ring or a fused polycyclic aromatic ring; R 5 and R 6 are independently selected from the group consisting of (CH 2 ) p X where p is 1-18 and X is a functional group that reacts with amino, hydroxy or sulfhydryl nucleophiles; R 7 and R 8 are independently selected from the group consisting of hydrogen, C1-C10 alkyl and where R 7 and R 8 are taken together to form a five- or six- membered heterocyclic ring; Y is selected from the group consisting of C(CH 3 ) 2 and S; and Z is selected from the group consisting of C(CH 3 ) 2 and S.
Claim 14
Dependent Claim
37 words
A cyanine dye according to claim 11 wherein R 7 and R 8 are taken together to form a ring selected from the group consisting of pyridinium, imidazolium, pyrrolium, pyrazolium, pyrazinium, pyrimidinium, pyridazinium, purinium, quinolinium and isoquinolinium.
Claim 15
Dependent Claim
23 words
A cyanine dye according to claim 12 wherein R 7 and R 8 are taken together to form a pyridinium or imidazolium ring.
Claim 16
Dependent Claim
34 words
A cyanine dye according to claim 13 wherein R 7 and R 8 are taken together to form a substituent selected from the group consisting of: a 4-dimethylaminopyridinium, 4-(4-morpholinyl) pyridinium, and a 1-methylimidazolium substitutent.
Claim 17
Dependent Claim
57 words
A cyanine dye according to claim 11 where X is independently selected from the group consisting of carboxylic acids, acid halides, sulfonic acids, esters, aldehydes, disulfides, isothiocyanates, isocyanates, monochlorotriazine, dichlorotriazine, mono- or di-halogen substituted pyridines, mono- or di-halogen substituted diazines, maleimide, aziridines, sulfonyl halides, hydroxysuccinimide esters, hydroxysulfosuccinimide esters, imido esters, hydrazines, azidonitrophenyl, azides, 3-(2-pyridyl dithio)propionamide and glyoxal.
Claim 18
Dependent Claim
13 words
A cyanine dye according to claim 15 where X is a carboxylic acid.
Claim 19
Dependent Claim
37 words
A cyanine dye according to claim 15 wherein R 7 and R 8 are taken together to form a ring selected from the group consisting of pyridinium, imidazolium, pyrrolium, pyrazolium, pyrazinium, pyrimidinium, pyridazinium, purinium, quinolinium and isoquinolinium.
Claim 20
Dependent Claim
18 words
A cyanine dye according to claim 11 wherein Y and Z each are C(CH 3 ) 2 .
Claim 21
Dependent Claim
10 words
A cyanine dye selected from the group consisting of: ##STR29##
Claim 22
Dependent Claim
10 words
A cyanine dye selected from the group consisting of: ##STR29##
Claim 23
Dependent Claim
208 words
Method for fluorescent labeling a molecule comprising: labeling a molecule having an amino, hydroxy or sulfhydryl functional group with a cyanine dye having the formula ##STR30## wherein n and m are each independently either 0, 1, 2 or 3; R 1 and R 2 are taken together to form an aromatic ring or a fused polycyclic aromatic ring; R 3 and R 4 are taken together to form an aromatic ring or a fused polycyclic aromatic ring; R 5 and R 6 are independently selected from the group consisting of (CH 2 ) p X where p is 1-18 and X is a functional group that reacts with amino, hydroxy or sulfhydryl nucleophiles; R 7 and R 8 are independently selected from the group consisting of hydrogen, C1-C10 alkyl and where R 7 and R 8 are taken together to form a five- or six- membered heterocyclic ring; R 9 are each independently selected from the group consisting of hydrogen, alkyl and where more than one R 9 are taken together to form a five- or six- membered ring; Y is selected from the group consisting of C(CH 3 ) 2 and S; and Z is selected from the group consisting of C(CH 3 ) 2 and S.
Claim 24
Dependent Claim
208 words
Method for fluorescent labeling a molecule comprising: labeling a molecule having an amino, hydroxy or sulfhydryl functional group with a cyanine dye having the formula ##STR30## wherein n and m are each independently either 0, 1, 2 or 3; R 1 and R 2 are taken together to form an aromatic ring or a fused polycyclic aromatic ring; R 3 and R 4 are taken together to form an aromatic ring or a fused polycyclic aromatic ring; R 5 and R 6 are independently selected from the group consisting of (CH 2 ) p X where p is 1-18 and X is a functional group that reacts with amino, hydroxy or sulfhydryl nucleophiles; R 7 and R 8 are independently selected from the group consisting of hydrogen, C1-C10 alkyl and where R 7 and R 8 are taken together to form a five- or six- membered heterocyclic ring; R 9 are each independently selected from the group consisting of hydrogen, alkyl and where more than one R 9 are taken together to form a five- or six- membered ring; Y is selected from the group consisting of C(CH 3 ) 2 and S; and Z is selected from the group consisting of C(CH 3 ) 2 and S.
Claim 25
Dependent Claim
21 words
A method according to claim 20 wherein the molecule is selected from the group consisting of antibodies, DNA, carbohydrates and cells.
Claim 26
Dependent Claim
40 words
A method according to claim 20 wherein R 7 and R 8 of the cyanine dye are taken together to form a ring selected from the group consisting of pyridinium, imidazolium, pyrrolium, pyrazolium, pyrazinium, pyrimidinium, pyridazinium, purinium, quinolinium and isoquinolinium.
Claim 27
Dependent Claim
26 words
A method according to claim 22 wherein R 7 and R 8 of the cyanine dye are taken together to form a pyridinium or imidazolium ring.
Claim 28
Dependent Claim
37 words
A method according to claim 23 wherein R 7 and R 8 of the cyanine dye are taken together to form a substituent selected from the group consisting of: a 4-dimethylaminopyridinium, 4-(4-morpholinyl) pyridinium, and a 1-methylimidazolium substitutent.
Claim 29
Dependent Claim
15 words
A method according to claim 20 wherein (n+m) is less than or equal to 3.
Claim 30
Dependent Claim
10 words
A method according to claim 25 wherein n=1 and m=1.
Claim 31
Dependent Claim
20 words
A method according to claim 20 wherein Y and Z of the cyanine dye are C(CH 3 ) 2 .
Claim 32
Dependent Claim
171 words
Method for fluorescent labeling a molecule comprising: labeling a molecule having an amino, hydroxy or sulfhydryl functional group with a cyanine dye having the formula ##STR31## wherein r is 1, 2 or 3; R 1 and R 2 are taken together to form an aromatic ring or a fused polycyclic aromatic ring; R 3 and R 4 are taken together to form an aromatic ring or a fused polycyclic aromatic ring; R 5 and R 6 are independently selected from the group consisting of (CH 2 ) p X where p is 1-18 and X is a functional group that reacts with amino, hydroxy or sulfhydryl nucleophiles; R 7 and R 8 are independently selected from the group consisting of hydrogen, C1-C10 alkyl and where R 7 and R 8 are taken together to form a five- or six- membered heterocyclic ring; Y is selected from the group consisting of C(CH 3 ) 2 and S; and Z is selected from the group consisting of C(CH 3 ) 2 and S.
Claim 33
Dependent Claim
171 words
Method for fluorescent labeling a molecule comprising: labeling a molecule having an amino, hydroxy or sulfhydryl functional group with a cyanine dye having the formula ##STR31## wherein r is 1, 2 or 3; R 1 and R 2 are taken together to form an aromatic ring or a fused polycyclic aromatic ring; R 3 and R 4 are taken together to form an aromatic ring or a fused polycyclic aromatic ring; R 5 and R 6 are independently selected from the group consisting of (CH 2 ) p X where p is 1-18 and X is a functional group that reacts with amino, hydroxy or sulfhydryl nucleophiles; R 7 and R 8 are independently selected from the group consisting of hydrogen, C1-C10 alkyl and where R 7 and R 8 are taken together to form a five- or six- membered heterocyclic ring; Y is selected from the group consisting of C(CH 3 ) 2 and S; and Z is selected from the group consisting of C(CH 3 ) 2 and S.
Claim 34
Dependent Claim
36 words
A method according to claim 28 wherein R 7 and R 8 are taken together to form a ring selected from the group consisting of pyridinium, imidazolium, pyrrolium, pyrazolium, pyrazinium, pyrimidinium, pyridazinium, purinium, quinolinium and isoquinolinium.
Claim 35
Dependent Claim
22 words
A method according to claim 29 wherein R 7 and R 8 are taken together to form a pyridinium or imidazolium ring.
Claim 36
Dependent Claim
32 words
A method according to claim 30 wherein R 7 and R 8 are taken together to form a substituent selected from the group consisting of: a 4-dimethylaminopyridinium, 4-(4-morpholinyl)pyridinium, and a 1-methylimidazolium substitutent.
Claim 37
Dependent Claim
56 words
A method according to claim 28 where X is independently selected from the group consisting of carboxylic acids, acid halides, sulfonic acids, esters, aldehydes, disulfides, isothiocyanates, isocyanates, monochlorotriazine, dichlorotriazine, mono- or di-halogen substituted pyridines, mono- or di-halogen substituted diazines, maleimide, aziridines, sulfonyl halides, hydroxysuccinimide esters, hydroxysulfosuccinimide esters, imido esters, hydrazines, azidonitrophenyl, azides, 3-(2-pyridyl dithio)propionamide and glyoxal.
Claim 38
Dependent Claim
12 words
A method according to claim 32 where X is a carboxylic acid.
Claim 39
Dependent Claim
36 words
A method according to claim 33 wherein R 7 and R 8 are taken together to form a ring selected from the group consisting of pyridinium, imidazolium, pyrrolium, pyrazolium, pyrazinium, pyrimidinium, pyridazinium, purinium, quinolinium and isoquinolinium.
Claim 40
Dependent Claim
17 words
A method according to claim 28 wherein Y and Z each are C(CH 3 ) 2 .
Claim 41
Dependent Claim
29 words
Method for fluorescent labeling a molecule comprising: labeling a molecule having an amino, hydroxy or sulfhydryl functional group with a cyanine dye selected from the group consisting of: ##STR32##
Claim 42
Dependent Claim
29 words
Method for fluorescent labeling a molecule comprising: labeling a molecule having an amino, hydroxy or sulfhydryl functional group with a cyanine dye selected from the group consisting of: ##STR32##
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