Large stoke shift dye used for optical imaging
The present invention relates to a diagnostic contrast agent comprising a water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye having a Stoke shift of greater than 50 and represented by five general formulae. The present invention also relates to a method for making a dye-conjugate utilizing the novel dye and a method of identifying a biological compound using the novel dye conjugate.
1. A water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye compound having a Stokes shift of greater than 50 nm and represented by at least one of the following five general formulae:
wherein:
R1 and R2 are substituted alkyl groups and may together form a ring and at least one of R1 or R2 comprises a linking group selected from the group comprising COOH, NH2, maleimide, thiol, isocyanate, isothiocyanate, disulfide, alkynyl, azidoyl, or trialkoxysilane, wherein the linking group may form part of the ring;
A is Ra—C—Rb, wherein Ra and Rb are substituted or unsubstituted alkyl groups;
Rc is hydrogen or SO3-, aryl, alkyl, alkoxy, or halogen;
Rd is alkyl or (CH2)nSO3- where n=2 to 4,
wherein:
R1 and R2 are substituted alkyl groups and are together capable of forming a ring, and at least one of R1 or R2 comprises a linking group selected from the group comprising COOH, NH2, maleimide, thiol, isocyanate, isothiocyanate, disulfide, alkynyl, azidoyl, or trialkoxysilane, wherein the linking group may form part of the ring;
A is Ra—C—Rb, wherein Ra and Rb are substituted or unsubstituted alkyl groups;
Rc is hydrogen or SO3-, aryl, alkyl, alkoxy, or halogen;
Rd is alkyl or (CH2)nSO3- where n=2 to 4,
wherein:
A is Ra—C—Rb;
R3, R4, Ra, and Rb are substituted or unsubstituted alkyl groups capable of joining together to form a ring;
R6 is a SO3-;
R5 is a substituted alkyl group and at least one of the substituents is selected from the group comprising OH, NH2, COOH, maleimide, thiol, isocyante, isothiocyanate, disulfide, alkynyl, azidoyl, or trialkoxysilane;
wherein:
A is Ra—C—Rb;
R3, R4, Ra, and Rb are substituted or unsubstituted alkyl groups capable of joining together to form a ring;
at least one of Rc and Rc′ is a SO3-;
R5 is a substituted alkyl group and at least one of the substituents is selected from the group consisting of OH, NH2, COOH, maleimide, thiol, isocyante, isothiocyanate, disulfide, alkynyl, azidoyl, or trialkoxysilane;
Rc is hydrogen or SO3-, aryl, alkyl, alkoxy, or halogen; and
wherein:
A is Ra—C—Rb;
R3, R4, Ra, and Rb are substituted or unsubstituted alkyl groups capable of joining together to form a ring;
R7 is a COOH;
R5 is substituted alkyl and contains a SO3- group.
2. The water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye compound of claim 1 , wherein the dye compound comprises a carboxyethylpiperazine (enamine) bridging group.
3. The water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye compound of claim 1 wherein Ra and Rb are methyl.
4. The water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye compound of claim 1 wherein at least one of R1, R2, R3, R4 independently represents COOH.
5. The water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye compound of claim 1 wherein said Stokes shift is from 70 to 140 nm.
6. The water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye compound of claim 1 wherein said dye compound has a maximum excitation wavelength between 500 and 900 nm.
7. The water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye compound of claim 1 , wherein said dye compound has a maximum excitation wavelength between 500 and 900 nm and a Stokes shift of at least 70 nm.
8. The water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye compound of claim 1 , wherein said dye compound is:
9. The water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye compound of claim 1 , wherein said dye compound is at least one member of the group represented by:
10. The water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye compound of claim 1 , wherein said dye compound is attached to biocompatible particles, biocompatible beads, microbeads or nanoparticles.
11. The water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye compound of claim 1 , wherein said dye compound is attached to peptides, proteins, antibodies or oligonucleotides.
12. The water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye compound of claim 1 , wherein said dye compound is attached to at least one drug.
13. The water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye compound of claim 1 , wherein said dye compound is attached to at least one cell.
14. The water dispersible, near-infrared tricarbocyanine, enamine-functionalized dye compound of claim 1 wherein said dye compound is attached to at least one non-biological material selected from the group consisting of soluble polymers, polymeric particles, glass and polymeric surfaces, and monomers.