Near-infrared fluorescent dyes with large stokes shifts

A method for selectively detecting an analyte in a biological fluid, comprising:

• (a) combining a compound according to general formula (III) or (IV) with a biological fluid to form a solution
• where each bond depicted as “” is a single or double bond as needed to satisfy valence requirements;
• X1 is O, S, or N(H);
• R6 is hydroxyl, amino, alkyl amino, or —NHRc when the bond between R6 and ring A is a single bond, or R6 is oxygen, imino, iminium, alkyl imino, or alkyl iminium when the bond between R6 and ring A is a double bond, where RC is
• R7 is hydrogen or halogen;
• R9-R12 independently are hydrogen, lower alkyl, carboxyl, amino, or —SO3H;
• R13 is hydrogen, lower alkyl, lower alkoxy, —SO3H or —COOR14 where R14 is hydrogen or lower alkyl and the bond depicted as “” in ring B is a double bond, or R13 is one or more atoms forming a ring system with rings B and D and the bond depicted as “” in ring B is a single bond;
• R16 and R18 independently are hydrogen, hydroxyl, thiol, oxygen, lower alkoxy, amino, alkyl amino, or —NHRc, and at least one of R16 and R18 is other than hydrogen;
• R19 and R21 independently are hydrogen, hydroxyl, thiol, oxygen, amino, alkyl amino, imino, iminium, alkyl imino, alkyl iminium, or —NHRc where Rc is as defined above, and at least one of R19 and R21 is other than hydrogen;
• and
• wherein if X1 is oxygen in general formula (III), then R6 is other than oxygen or alkyl amino, or R13 is other than one or more atoms forming a ring system with rings B and D, or R16 is other than hydroxyl or hydrogen, or R18 is other than hydroxyl or hydrogen, or at least one of R7, R9, R10, R11, R12, R13 is other than hydrogen, or
• if the compound has a chemical structure according to general formula (IV), then at least one of R9-R13, R16, R18, R19, or R21is other than hydrogen, hydroxyl, halogen, oxygen, lower alkyl, amino, or thiol, or R13 is one or more atoms forming a ring system with rings B and D and the bond depicted as “” in ring B is a single bond;
• (b) exposing the solution to a light source;
• and
• (c) detecting the analyte by detecting fluorescence from the compound, wherein the analyte comprises cysteine, homocysteine, glutathione, succinyl-5-amino-4-imidazolecarboxamide riboside, succinyladenosine, or a combination thereof.