Swallowtail motifs for imparting water solubility to porphyrinic compounds

Abstract

Porphyrinic compounds that contain solubilizing groups are described, along with methods of making and using the same and compositions comprising such compounds. Examples of such compounds include compounds of Formula I: wherein: Z is a porphyrinic macrocycle, Alk 1 and Alk 2 are each independently an alkylidene chain; L is a linking group or is absent; R 1 is preferably an ionic group or polar group; R 2 is an ionic group, polar group, bioconjugatable group, or targeting group; R 3 is present or absent and when present is a halo group, bioconjugatable group, or targeting group, n is O or 1 (that is, the CH group is present, or Alk 1 and Alk 2 are bonded directly to a carbon of the porphyrinic macrocycle Z); or a salt thereof.

1 . A compound of Formula I: 
       
         
           
           
               
               
           
         
       
       wherein:
 Alk 1  and Alk 2  are each independently a C1-C50 alkylidene chain; 
 Z is a porphyrinic macrocycle; 
 L is a linking group or is absent; 
 R 1  is an ionic group, polar group, bioconjugatable group, or targeting group; 
 R 2  is an ionic group, polar group, bioconjugatable group, or targeting group; 
 R 3  is present or absent and when present is a halo group, bioconjugatable group, or targeting group, 
 n is O or 1; 
 or a salt thereof. 
 
     
     
         2 . The compound of  claim 1 , wherein said compound has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         3 . The compound of  claim 1 , wherein Z is selected from the group consisting of porphyrins, chlorins, bacteriochlorins, and isobacteriochlorins. 
     
     
         4 . The compound of  claim 1 , wherein Z is selected from the group consisting of:
 (a) porphyrins of Formula Ia:   
       
         
           
           
               
               
           
         
         (b) chlorins of Formula Ib: 
       
       
         
           
           
               
               
           
         
         (c) bacteriochlorins of Formula Ic 
       
       
         
           
           
               
               
           
         
       
       wherein:
 M is a metal or is absent; 
 X 1 , X 2 , X 3  and X 4  are each independently selected from the group consisting of Se, NH, CH 2 , O and S; 
 R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , and R 28  are each independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, heterocyclo, heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, aryl, aryloxy, arylalkyl, arylalkenyl, arylalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, alkoxy, halo, mercapto, azido, cyano, acyl, formyl, carboxylic acid, acylamino, ester, amide, hydroxyl, nitro, alkylthio, amino, alkylamino, arylalkylamino, disubstituted amino, acyloxy, sulfoxyl, sulfonyl, sulfonate, sulfonic acid, sulfonamide, urea, alkoxylacylamino, aminoacyloxy, linking groups, surface attachment groups, bioconjugatable groups, targeting groups, and groups of Formula II: 
 
       
         
           
           
               
               
           
         
         wherein R 4  and R 5  are each independently an ionic group or polar group, and Alk 3  and Alk 4  are each independently a C1-C50 alkylidene chain; 
         wherein each of R 11  and R 12 , R 13  and R 14 , R 21  and R 22 , or R 23  and R 24  can together form ═O; 
         and wherein each of R 11  and R 12 , R 13  and R 14 , R 21  and R 22 , or R 23  and R 24 , can together form spiroalkyl; 
         subject to the proviso that at least one of R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , and R 28  is a bond to L and at least one thereof is a bond to said CH group of Formula I; 
         and salts thereof. 
       
     
     
         5 . The compound of  claim 4 , wherein one of R 15 , R 18 , R 25  and R 28  is a bond to said CH group of Formula I. 
     
     
         6 . The compound of  claim 5 , wherein said compound is a porphyrin of formula Ia or a chlorin of formula II). 
     
     
         7 . The compound of  claim 4 , wherein:
 R 15  is a bond to L and R 25  is a bond to said CH group of Formula I;   R 25  is a bond to L and R 15  is a bond to said CH group of Formula I;   R 18  is a bond to L and R 28  is a bond to said CH group of Formula I; or   R 28  is a bond to L and R 18  is a bond to said CH group of Formula I.   
     
     
         8 . The compound of  claim 7 , wherein said compound is a porphyrin of formula Ia or chlorin of formula Ib. 
     
     
         9 . The compound of  claim 4 , wherein:
 R 15  is a bond to L and R 18  is a bond to said CH group of Formula I;   R 18  is a bond to L and R 25  is a bond to said CH group of Formula I;   R 25  is a bond to L and R 28  is a bond to said CH group of Formula I; or   R 28  is a bond to L and R 15  is a bond to said CH group of Formula I.   
     
     
         10 . The compound of  claim 9 , wherein said compound is a porphyrin of formula Ia or chlorin of formula Ib. 
     
     
         11 . The compound of  claim 4 , wherein:
 R 11 , R 12 , R 13 , R 14 , R 16 , R 17 , R 21 , R 22 , R 23 , R 24 , R 27  one of R K or R is a bond to said CH group of Formula I.   
     
     
         12 . The compound of  claim 11 , wherein said compound is a bacteriochlorin of Formula Ic. 
     
     
         13 . The compound of  claim 4 , wherein:
 one of R 11 , R 12 , R 13 , R 14 , R 16 , or R 17  is a bond to L, and one of R 21 , R 22 , R 23 , R 24 , R 26 , or R 27  is a bond to said CH group of Formula I.   
     
     
         14 . The compound of  claim 13 , wherein said compound is a bacteriochlorin of formula Ic. 
     
     
         15 . The compound of  claim 4 , wherein:
 one of R 16 , R 17 , R 26 , or R 27  is a bond to said CH group of Formula I.   
     
     
         16 . The compound of  claim 15 , wherein said compound is a bacteriochlorin of formula Ic. 
     
     
         17 . The compound of  claim 4 , wherein:
 R 16  is a bond to L and R 26  is a bond to said CH group of Formula I;   R 26  is a bond to L and R 16  is a bond to said CH group of Formula I;   R 17  is a bond to L and R 27  is a bond to said CH group of Formula I; or   R 27  is a bond to L and R 17  is a bond to said CH group of Formula I.   
     
     
         18 . The compound of  claim 17 , wherein said compound is a bacteriochlorin of formula Ic. 
     
     
         19 . The compound of  claim 18 , wherein M is present and is selected from the group consisting of Pd, Pt, Mg, Zn, Al, Ga, In, Sn, Cu, Ni, and Au. 
     
     
         20 - 35 . (canceled) 
     
     
         36 . In a method of detecting cells or particles by flow cytometry, wherein said cells or particles are labelled with a detectable luminescent compound, the improvement comprising utilizing a compound of  claim 1  as the detectable luminescent compound. 
     
     
         37 - 40 . (canceled) 
     
     
         41 . A chlorin of Formula Va or bacteriochlorin of Formula Vb: 
       
         
           
           
               
               
           
         
       
       wherein:
 M is a metal or is absent; 
 X 1 , X 2 , X 3  and X 4  are each independently selected from the group consisting of Se, NH, CH 2 , O and S; 
 at least one pair of R 11  and R 12 , R 13  and R 14 , R 21  and R 22 , and R 23  and R 24  are both independently selected Alk′R′, wherein Alk′ is a C1-C50 alkylidene chain, and R is an ionic group, polar group, bioconjugatable group, or targeting group; 
 R 11 , R 12 , R 15 , R 16 , R 17 , R 18 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , and R 28  are as described above or otherwise each independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, heterocyclo, heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, aryl, aryloxy, arylalkyl, arylalkenyl, arylalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, alkoxy, halo, mercapto, azido, cyano, acyl, formyl, carboxylic acid, acylamino, ester, amide, hydroxyl, nitro, alkylthio, amino, alkylamino, arylalkylamino, disubstituted amino, acyloxy, sulfoxyl, sulfonyl, sulfonate, sulfonic acid, sulfonamide, urea, alkoxylacylamino, aminoacyloxy, linking groups, surface attachment groups, and groups of Formula II: 
 
       
         
           
           
               
               
           
         
       
       wherein R 4  and R 5  are each independently an ionic group or polar group, and Alk 3  and Alk 4  are each independently a C1-C50 alkylidene chain;
 wherein each of R 11  and R 12 , R 13  and R 14 , R 21  and R 22 , or R 23  and R 24  can together form ═O; 
 and wherein each of R 11  and R 12 , R 13  and R 14 , R 21  and R 22 , or R 23  and R 24 , can together form spiroalkyl; 
 or R 23  is Alk 41 R 41  wherein Alk 41  is a C1-C50 alkylidene chain, and R 41  is an ionic group, polar group, bioconjugatable group, or targeting group; 
 or R 24  is Alk 42 R 42  wherein Alk 42  is a C1-C50 alkylidene chain, and R 42  is an ionic group, polar group, bioconjugatable group or targeting group; 
 or a salt thereof. 
 
     
     
         42 . The compound of  claim 41 , subject to the proviso that R 21  and R 22 , or R 23  and R 24  are not both H when said compound is a bacteriochlorin of Formula Vb. 
     
     
         43 . The compound of  claim 41 , wherein M is present and is selected from the group consisting of Pd, Pt, Mg, Zn, Al, Ga, In, Sn, Cu, Ni, and Au. 
     
     
         44 - 55 . (canceled) 
     
     
         56 . In a method of detecting cells or particles by flow cytometry, wherein said cells or particles are labelled with a detectable luminescent compound, the improvement comprising utilizing a compound of  claim 41  as the detectable luminescent compound. 
     
     
         57 . (canceled)