Charge-balanced imaging agents

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 -L-TL, where TL is a targeting ligand comprising at least one binding moiety that binds to a biological target;
• L has the formula:
• E is absent or S;
• Q is (CH2)q or a non-ionic oligomeric or polymeric solubilizing moiety;
• J is C(O), C(O)O, or C(O)NH;
• R17, R18, R19, and R12 are independently selected from H, an ionic group, a non-ionic oligomeric or polymeric solubilizing group, halo, cyano, nitro, C1-4 alkyl, C1-4 alkoxy, and C1-4 haloalkyl;
• q is 0, 1, 2, 3, 4, 5, 6, 7, or 8;
• R1, R2, R3, R4, R5, R6, R7, and R8 are independently selected from H, an ionic group, a non-ionic oligomeric or polymeric solubilizing group, halo, C1-6 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 C1-4 haloalkyl;
• or two adjacent R1, R2, R3, R4, R5, R6, R7, and R8 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 C1-4 haloalkyl;
• R9, and R10, are independently selected from an ionic group, a non-ionic oligomeric or polymeric solubilizing group, C1-6 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 C1-4 haloalkyl;
• R11 and R12 are independently selected from C1-4 alkyl optionally substituted with 1, 2, or 3 halo;
• R13 and R14 are independently selected from C1-4 alkyl optionally substituted with 1, 2, or 3 halo;
• R15 and R16 are independently selected from H and C1-6 alkyl;
• R22, R23, R24, R25, R26, and R27 are independently selected from independently an ionic group, a non-ionic oligomeric or polymeric solubilizing group, halo, C1-6 alkyl, aryl, and heteroaryl;
• and
• v is 0, 1, 2, 3, 4, or 5,
• wherein at least one of R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 is an ionic group,
• or an ester thereof, which permits covalent conjugation of the fluorophore to targeting ligands.