Dichromic fluorescent compounds

Abstract

The present invention provides dichromic fluorescent compounds, as well as processes for making and methods for using the dichromic fluorescent compounds.

1 . A dichromic compound, the compound comprising:
   A-L-B   
       wherein:
 A and B are each either structurally symmetrical moieties, or are each structurally asymmetrical moieties; 
 L is a linker comprising a chromophore; and 
 the compound further comprising R 1  and R 2 , wherein R 1  and R 2  are structurally distinct groups that are each either conjugated to the compound comprising structurally symmetrical A and B moieties in a manner that yields asymmetry such that the compound has two distinct fluorescence lifetimes at two different emission wavelengths; or R 1  and R 2  are each conjugated to the compound comprising structurally asymmetrical A and B moieties in a manner that yields symmetry such that the compound has two distinct fluorescence lifetimes at two different emission wavelengths. 
 
     
     
         2 . The dichromic compound of  claim 1 , the compound comprising Formula (I): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  and R 2  are independently selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, amino acid sequence, and nucleic acid sequence; provided that R 1  and R 2  are different groups; 
 X is a heteroatom selected from the group consisting of nitrogen, phosphorus, silicon, and sulfur; 
 X 1  and X 2  are atoms independently selected from the group consisting of carbon, nitrogen, phosphorus, silicon, sulfur, and oxygen; 
 L is a linker comprising a chromophore; and 
 R 3 , R 4 , R 5 , and R 6  are selected from the group consisting of hydrogen, halogen, hydrocarbyl, and substituted hydrocarbyl; provided that R 3  and R 4  and R 5  and R 6  may form a ring or a ring system. 
 
     
     
         3 . The dichromic compound of  claim 2 , the compound comprising Formula (Ia): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  and R 2  are independently selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, amino acid sequence, and nucleic acid sequence; provided that R 1  and R 2  are different groups; 
 X 1  and X 2  are atoms independently selected from the group consisting of carbon, nitrogen, phosphorus, silicon, sulfur, and oxygen; 
 L is a linker comprising a chromophore; and 
 R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10  are selected from the group consisting of hydrogen, halogen, hydrocarbyl and substituted hydrocarbyl; provided that any of R 3  and R 4 , R 4  and R 5 , R 5  and R 6 , R 7  and R 8 , R 8  and R 9 , and R 9  and R 10  may form a ring or a ring system. 
 
     
     
         4 . The dichromic compound of  claim 3 , the compound comprising Formula (Ib): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  and R 2  are independently selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, amino acid sequence, and nucleic acid sequence; provided that R 1  and R 2  are different groups; 
 R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , and R 18  are each independently selected from the group consisting of hydrogen, halogen, hydrocarbyl and substituted hydrocarbyl; and 
 n is an integer from 0 to 10. 
 
     
     
         5 . The compound of  claim 4 , the compound comprising Formula (Ic): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  and R 2  are independently selected from the group consisting of hydrogen, amide, amino, carboxyl, halogen, hydroxy, phosphate, sulfonate, thiol, azido, alkyne, amino acid sequence, and nucleic acid sequence; provided that R 1  and R 2  are different groups; 
 R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , and R 18  are each independently selected from the group consisting of hydrogen, halogen, hydrocarbyl and substituted hydrocarbyl; 
 m is an integer from 1 to 10; and 
 n is an integer from 1 to 10. 
 
     
     
         6 . The dichromic compound of  claim 5 , wherein R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 13 , R 14 , R 15 , R 16 , R 17 , and R 13  are each hydrogen; and R 9 , R 10 , R 11 , and R 12  are each methyl. 
     
     
         7 . The dichromic compound of  claim 6 , wherein the compound is selected from the group consisting of A-1, A-2, A-3, and A-4: 
       
         
           
                 
                 
               
                     
                 
                   A-1 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   A-2 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   A-3 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   A-4 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
             
                
               
               
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         8 . The dichromic compound of  claim 1 , the compound comprising Formula (II): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  and R 2  are independently selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, amino acid sequence, and nucleic acid sequence; provided that R 1  and R 2  are different groups; 
 R 3 , R 4 , R 5 , and R 6  are selected from the group consisting of halogen, hydrocarbyl and substituted hydrocarbyl; provided that R 3  and R 4  and R 5  and R 6  may form a ring or a ring system. 
 R 19  and R 20  are independently selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, amino acid sequence, and nucleic acid sequence; 
 X is a heteroatom selected from the group consisting of nitrogen, phosphorus, silicon, and sulfur; 
 X 1  and X 2  are atoms independently selected from the group consisting of carbon, nitrogen, phosphorus, silicon, sulfur, and oxygen; 
 Z is a cyclic group selected from the group consisting of a carbocyclic ring and a heterocyclic ring; 
 m is an integer from 1 to 3; and 
 n is an integer from 1 to 3. 
 
     
     
         9 . The dichromic compound of  claim 8 , the compound comprising Formula (IIa): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  and R 2  are independently selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, amino acid sequence, and nucleic acid sequence; provided that R 1  and R 2  are different groups; 
 R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10  are selected from the group consisting of hydrogen, halogen, hydrocarbyl and substituted hydrocarbyl; provided that any of R 3  and R 4 , R 4  and R 5 , R 5  and R 6 , R 7  and R 8 , R 8  and R 9 , and R 9  and R 10  may form a ring or a ring system; 
 R 19  and R 20  are independently selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, amino acid sequence, and nucleic acid sequence; 
 X 1  and X 2  are atoms independently selected from the group consisting of carbon, nitrogen, phosphorus, silicon, sulfur, and oxygen; 
 Z is a cyclic group selected from the group consisting of a carbocyclic ring and a heterocyclic ring; 
 n is an integer from 1 to 3; and 
 m is an integer from 1 to 3. 
 
     
     
         10 . The dichromic compound of  claim 9 , the compound comprising Formula (IIb): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  and R 2  are independently selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, amino acid sequence, and nucleic acid sequence; provided that R 1  and R 2  are different groups; 
 R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , and R 18  are each independently selected from the group consisting of hydrogen, halogen, hydrocarbyl and substituted hydrocarbyl; 
 R 19  and R 20  are independently selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, amino acid sequence, and nucleic acid sequence; 
 Z is a cyclic group selected from the group consisting of a carbocyclic ring and a heterocyclic ring; 
 m is an integer from 1 to 3; and 
 n is an integer from 1 to 3. 
 
     
     
         11 . The dichromic compound of  claim 10 , the compound comprising Formula (IIc): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  and R 2  are independently selected from the group consisting of hydrogen, amide, amino, carboxyl, halogen, hydroxy, phosphate, sulfonate, thiol, azido, alkyne, amino acid sequence, and nucleic acid sequence; provided that R 1  and R 2  are different groups; 
 R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 21 , R 22 , R 23 , R 24 , and R 25  are each independently selected from the group consisting of hydrogen, halogen, hydrocarbyl and substituted hydrocarbyl; 
 R 19  and R 20  are independently selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, amino acid sequence, and nucleic acid sequence; 
 m is an integer from 1 to 10; and 
 n is an integer from 1 to 10. 
 
     
     
         12 . The dichromic compound of  claim 11 , the compound comprising Formula (IId): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  and R 2  are independently selected from the group consisting of hydrogen, amide, amino, carboxyl, halogen, hydroxy, phosphate, sulfonate, thiol, azido, alkyne, amino acid sequence, and nucleic acid sequence; provided that R 1  and R 2  are different groups; 
 R 26  is selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, amino acid sequence, and nucleic acid sequence; 
 X 4  is a single bond or a heteroatom selected from the group consisting of sulfur, nitrogen, and oxygen; and 
 m is an integer from 1 to 10; and 
 n is an integer from 1 to 10. 
 
     
     
         13 . The dichromic compound of  claim 1 , wherein the two different emission wavelengths have absorption spectra from about 200 nm to about 1200 nm. 
     
     
         14 . The dichromic compound of  claim 1 , wherein the two different emission wavelengths are separated by about 25 nm to about 400 nm. 
     
     
         15 . A method for monitoring a biological event in a subject, the method comprising administering a dichromic compound to the subject and detecting whether the structural symmetry of the compound changes, thereby indicating the biological event; the dichromic compound comprising:
   A-L-B   
       wherein:
 A and B are either structurally symmetrical moieties or are each structurally asymmetrical moieties; 
 L is a linker comprising a chromophore; and 
 the compound further comprising R 1  and R 2 , wherein R 1  and R 2  are structurally distinct groups that are each either conjugated to the compound comprising structurally symmetrical A and B moieties in a manner that yields asymmetry such that the compound has two distinct fluorescence lifetimes at two different emission wavelengths; or R 1  and R 2  are each conjugated to the compound comprising structurally asymmetrical A and B moieties in a manner that yields symmetry such that the compound has two distinct fluorescence lifetimes at two different emission wavelengths. 
 
     
     
         16 . The method of  claim 15 , the dichromic compound comprising Formula (I): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  and R 2  are independently selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, amino acid sequence, and nucleic acid sequence; provided that R 1  and R 2  are different groups; 
 X is a heteroatom selected from the group consisting of nitrogen, phosphorus, silicon, and sulfur; 
 X 1  and X 2  are atoms independently selected from the group consisting of carbon, nitrogen, phosphorus, silicon, sulfur, and oxygen; 
 R 3 , R 4 , R 5 , and R 6  are selected from the group consisting of hydrogen, halogen, hydrocarbyl, and substituted hydrocarbyl; provided that R 3  and R 4  and R 5  and R 6  may form a ring or a ring system. 
 
     
     
         17 . The method of  claim 15 , the dichromic compound comprising Formula (II): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  and R 2  are independently selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, amino acid sequence, and nucleic acid sequence; provided that R 1  and R 2  are different groups; 
 R 3 , R 4 , R 5 , and R 6  are selected from the group consisting of hydrogen, halogen, hydrocarbyl and substituted hydrocarbyl; provided that R 3  and R 4  and R 5  and R 6  may form a ring or ring system. 
 R 19  and R 20  are independently selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, amino acid sequence, and nucleic acid sequence; 
 X is a heteroatom selected from the group consisting of nitrogen, phosphorus, silicon, and sulfur; 
 X 1  and X 2  are atoms independently selected from the group consisting of carbon, nitrogen, phosphorus, silicon, sulfur, and oxygen; 
 Z is a cyclic group selected from the group consisting of a carbocyclic ring and a heterocyclic ring; 
 m is an integer from 1 to 3; and 
 n is an integer from 1 to 3. 
 
     
     
         18 . A process for producing a dichromic compound, the compound comprising:
   A-L-B   
       wherein:
 A and B are either structurally symmetrical moieties or are each structurally asymmetrical moieties; L is a linker comprising a chromophore; the compound further comprising R 1  and R 2 ; the process comprising conjugating R 1  and R 2 , which are structurally distinct groups, to the compound comprising structurally symmetrical A and B moieties in a manner that yields asymmetry such that the compound has two distinct fluorescence lifetimes at two different emissions wavelengths; or conjugating R 1  and R 2  to the compound comprising structurally asymmetrical A and B moieties in a manner that yields symmetry such that the compound has two distinct fluorescence lifetimes at two different emissions wavelengths. 
 
     
     
         19 . The process of  claim 18 , the dichromic compound comprising Formula (I): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  and R 2  are independently selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, amino acid sequence, and nucleic acid sequence; provided that R 1  and R 2  are different groups; 
 X is a heteroatom selected from the group consisting of nitrogen, phosphorus, silicon, and sulfur; 
 X 1  and X 2  are atoms independently selected from the group consisting of carbon, nitrogen, phosphorus, silicon, sulfur, and oxygen; 
 R 3 , R 4 , R 5 , and R 6  are selected from the group consisting of hydrogen, halogen, hydrocarbyl, and substituted hydrocarbyl; provided that R 3  and R 4  and R 5  and R 6  may form a ring or ring system. 
 
     
     
         20 . The process of  claim 18 , the dichromic compound comprising Formula (II): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  and R 2  are independently selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, amino acid sequence, and nucleic acid sequence; provided that R 1  and R 2  are different groups; 
 R 3 , R 4 , R 5 , and R 6  are selected from the group consisting of hydrogen, halogen, hydrocarbyl and substituted hydrocarbyl; provided that R 3  and R 4  and R 5  and R 6  may form a ring or a ring system. 
 R 19  and R 20  are independently selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, amino acid sequence, and nucleic acid sequence; 
 X is a heteroatom selected from the group consisting of nitrogen, phosphorus, silicon, and sulfur; 
 X 1  and X 2  are atoms independently selected from the group consisting of carbon, nitrogen, phosphorus, silicon, sulfur, and oxygen; 
 Z is a cyclic group selected from the group consisting of a carbocyclic ring and a heterocyclic ring; 
 m is an integer from 1 to 3; and 
 n is an integer from 1 to 3.