Charged-balanced imaging agents

1. A method of imaging tissue or cells, the method comprising:

(a) contacting the tissue or cells with an imaging agent comprising a dye;

(b) irradiating the tissue or cells at a wavelength absorbed by the dye;

(c) detecting an optical signal from the irradiated tissue or cells, wherein the signal-to-background ratio of the detected optical signal is at least about 1.1, thereby imaging the tissue or cells;

wherein the dye has the formula V:

wherein:

G is independently selected from H, C 1-6 alkyl, a moiety comprising a linking group, and a moiety comprising a targeting ligand;

R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 are independently selected from H, an ionic group, a non-ionic oligomeric or polymeric solubilizing group, halo, C 1-6 alkyl, aryl, and heteroaryl, wherein said alkyl, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, 4, or 5 groups independently selected from halo, cyano, nitro, and C 1-4 haloalkyl;

or two adjacent R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 groups, together with the atoms to which they are attached, form a fused 5-7 membered aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group, each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, cyano, nitro, and C 1-4 haloalkyl;

R 9 , and R 10 , are independently selected from an ionic group, a non-ionic oligomeric or polymeric solubilizing group, C 1-6 alkyl, aryl, and heteroaryl, wherein said alkyl, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, 4, or 5 groups independently selected from halo, cyano, nitro, and C 1-4 haloalkyl;

R 11 and R 12 are independently selected from C 1-4 alkyl optionally substituted with 1, 2, or 3 halo;

R 13 and R 14 are independently selected from C 1-4 alkyl optionally substituted with 1, 2, or 3 halo;

R 15 and R 16 are independently selected from H and C 1-6 alkyl;

R 22 , R 23 , R 24 , R 25 , R 26 , and R 27 are independently selected from independently an ionic group, a non-ionic oligomeric or polymeric solubilizing group, halo, C 1-6 alkyl, aryl, and heteroaryl; and

n is −1, 0 or +1,

wherein at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 is an ionic group.

2. A dye, having the formula V:

wherein:

G is independently selected from H, C 1-6 alkyl, a moiety comprising a linking group, and a moiety comprising a targeting ligand;

R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 are independently selected from H, an ionic group, a non-ionic oligomeric or polymeric solubilizing group, halo, C 1-6 alkyl, aryl, and heteroaryl, wherein said alkyl, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, 4, or 5 groups independently selected from halo, cyano, nitro, and C 1-4 haloalkyl;

or two adjacent R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 groups, together with the atoms to which they are attached, form a fused 5-7 membered aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group, each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, cyano, nitro, and C 1-4 haloalkyl;

R 9 , and R 10 , are independently selected from an ionic group, a non-ionic oligomeric or polymeric solubilizing group, C 1-6 alkyl, aryl, and heteroaryl, wherein said alkyl, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, 4, or 5 groups independently selected from halo, cyano, nitro, and C 1-4 haloalkyl;

R 11 and R 12 are independently selected from C 1-4 alkyl optionally substituted with 1, 2, or 3 halo;

R 13 and R 14 are independently selected from C 1-4 alkyl optionally substituted with 1, 2, or 3 halo;

R 15 and R 16 are independently selected from H and C 1-6 alkyl;

R 22 , R 23 , R 24 , R 25 , R 26 , and R 27 are independently selected from independently an ionic group, a non-ionic oligomeric or polymeric solubilizing group, halo, C 1-6 alkyl, aryl, and heteroaryl; and

n is −1, 0 or +1,

wherein the ester is a conjugate of one or more of an ionic group and/or the linking group.

3. An ester conjugate of a dye, having the formula V:

wherein:

G is independently selected from H, C 1-6 alkyl, a moiety comprising a linking group, and a moiety comprising a targeting ligand;

R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 are independently selected from H, an ionic group, a non-ionic oligomeric or polymeric solubilizing group, halo, C 1-6 alkyl, aryl, and heteroaryl, wherein said alkyl, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, 4, or 5 groups independently selected from halo, cyano, nitro, and C 1-4 haloalkyl;

or two adjacent R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 groups, together with the atoms to which they are attached, form a fused 5-7 membered aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group, each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, cyano, nitro, and C 1-4 haloalkyl;

R 9 , and R 10 , are independently selected from an ionic group, a non-ionic oligomeric or polymeric solubilizing group, C 1-6 alkyl, aryl, and heteroaryl, wherein said alkyl, aryl, and heteroaryl groups are optionally substituted with 1, 2, 3, 4, or 5 groups independently selected from halo, cyano, nitro, and C 1-4 haloalkyl;

R 11 and R 12 are independently selected from C 1-4 alkyl optionally substituted with 1, 2, or 3 halo;

R 13 and R 14 are independently selected from C 1-4 alkyl optionally substituted with 1, 2, or 3 halo;

R 15 and R 16 are independently selected from H and C 1-6 alkyl;

R 22 , R 23 , R 24 , R 25 , R 26 , and R 27 are independently selected from independently an ionic group, a non-ionic oligomeric or polymeric solubilizing group, halo, C 1-6 alkyl, aryl, and heteroaryl; and

n is −1, 0 or +1,

wherein at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 is an ionic group;

wherein the ester conjugate permits covalent conjugation of the fluorophore to targeting ligands.

4. The ester conjugate of claim 3 , wherein the ester is an N-hydroxysuccinimide ester.