Formation and uses of europium

Abstract

An MRI contrast composition includes a liposome and a europium metal complex disposed within the liposome. The europium metal complex includes a europium metal ion and a multi-dentate ligand selected from the group consisting of cryptands and thiacryptands and one or more counter-ions that balances a charge of the europium metal ion and the multi-dentate ligand, the europium metal ion being switchable between a 2+ and 3+ oxidation state. The contrast composition advantageously provides an oxidation-responsive dual-mode contrast agent because it would enhance either T1-weighted images or CEST images depending on the oxidation state of Eu.

1 .- 34 . (canceled) 
     
     
         35 . A compound having formula II: 
       
         
           
           
               
               
           
         
         wherein: 
         n, o are each independently 1 or 2; 
         L 1  is a multi-dentate ligand moiety that bonds to Eu; 
         L 2  is a multi-dentate ligand moiety that bonds to Gd; 
         Xp are counter-ions to maintain charge neutrality; and 
         Sp is a spacer moiety that provides separation between Eu and Gd. 
       
     
     
         36 . The compound of  claim 35  wherein L 1  is has formula III: 
       
         
           
           
               
               
           
         
         Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , and Y 6  are each independently O or S; 
         R 1 , R 2 , R 3  are each independently H, C 1-12  alkyl, C 1-12  fluoroalkyl, Cl, F, Br, I, N(R) 2 , NH 2 , CH 2 CO 2 H, nitro, cyano, or C 6-14  aryl, C 5-14  hetereoaryl, or 5 and 6 membered rings formed by combining R 1  on adjacent carbon atoms or R 2  and R 3  on adjacent carbon atoms, ═O by combining R 1 , R 2 , or R 3  on the same carbon atom, ═S by combining R 1 , R 2 , or R 3  on the same carbon atom, or ═NR by combining R 1 , R 2 , or R 3  on the same carbon atom; and 
         R is H or C 1-12  alkyl with the proviso that at least one R 1 , R 2 , or R 3  is a bond to Sp or has a bond to Sp. 
       
     
     
         37 . The compound of  claim 35  wherein L 2  include a plurality of groups having the following formula: 
       
         
           
           
               
               
           
         
       
     
     
         38 . The compound of  claim 35  wherein L 2  includes a moiety having the following formula: 
       
         
           
           
               
               
           
         
       
     
     
         39 . The compound of  claim 35  having formula 5: 
       
         
           
           
               
               
           
         
       
     
     
         40 . The compound of  claim 35  having the following formula: