Nir to swir fluorescent compounds for imaging and detection

Abstract

This disclosure provides a family of compounds that absorb and fluoresce in the short wave infrared region (SWIR, optionally 1000 nm to 1300 nm), including hydrophilic compounds that exhibit absorption and emission spectral profiles in aqueous solutions substantially similar to those observed in organic solvents such as methanol or DMSO. The compounds can be chemically linked to biomolecules including proteins, nucleic acids, and therapeutic small molecules. The compounds are useful for imaging in a variety of medical, biological and diagnostic applications, including SWIR in vivo imaging of regions of interest within a mammal.

1 . A compound represented by one of the following structures: 
       
         
           
           
               
               
           
         
         or a salt thereof, wherein: 
         R 1  is independently for each occurrence, hydrogen substituted or unsubstituted C 1  to C 24  alkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, sulfonate, aryl sulfonate, alkyl sulfonate, taurine, carboxylate, amine, alkylamine, arylamine, alkylammonium, arylammonium, sulfonamide, halogen, hydroxy, amide, nitro, cyano, azide, O-alkyl, S-alkyl, silyl, trialkylsilyl, O-silyl, haloalkyl, alkylsulfhydryl, trifluoromethyl, hydrazide, substituted or unsubstituted aryl, heteroaryl, or heterocyclic (e.g. morpholine) alkynyl, carboxyalkyl, aminoalkyl, haloalkyl, azidoalkyl, amide, amino acid, or peptide, O, S, N, P, Si, C, (C═C), or L; 
         L is absent or is a linker moiety, optionally bearing a functional group or reactive group, wherein said functional group or reactive group is a carboxylate, carboxyalkyl, maleimide, succinimidyl ester, carboxamide, propargyl, azidoalkyl, alkyne, isothiocyanate, of —NH 2 —OH, —SH, —SO 3 H, carboxyl, —COCl, —CONHNH 2 , acetoxymethyl esters, substituted and unsubstituted N-hydroxysuccinimidyl esters, substituted and unsubstituted N-hydroxysulfosuccinimido esters, nitro- or fluoro or phenol esters, azide, —COCH 2 I, phosphoramidite, phthalamido, acyl fluoride, acyl chloride, acyl azide, tyramide, cinnamamide, hydroxycinnamamide, aldehyde, ketone, phosphoramidite, isocyanate, isothiocyanate, sulfonyl chloride, maleimide or biotin; 
         R 2  is a substituted or unsubstituted C 1  to C 24  alkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, aryl sulfonate, C 1  to C 24  alkyl sulfonate, C 1 -C 24  alkyl carboxylate, aryl carboxylate, C 1 -C 24  alkylamine, arylamine, C 1 -C 24  alkylammonium, arylammonium, or substituted or unsubstituted polyethylene glycol. 
       
     
     
         2 . The compound of  claim 1 , wherein R 2  is a substituted or unsubstituted C 1  to C 24  alkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted aryl, aryl sulfonate, C 1  to C 24  alkyl sulfonate, C 1 -C 24  alkyl carboxylate, or aryl carboxylate. 
     
     
         3 . The compound of  claim 1 , wherein R 1  is in each occurrence a sulfonate, alkyl sulfonate, arylsulfonate or taurine. 
     
     
         4 . The compound of  claim 1 , wherein:
 R 1  is in each occurrence a sulfonate, alkyl sulfonate, arylsulfonate or taurine; and   R 2  is a substituted or unsubstituted C 1  to C 24  alkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted aryl, aryl sulfonate, C 1  to C 24  alkyl sulfonate, C 1 -C 24  alkyl carboxylate, or aryl carboxylate.   
     
     
         5 . The compound of  claim 4 , wherein R 1  in each occurrence is a sulfonate.