Cleavable agents

Abstract

The present disclosure is directed to a cleavable agent for enhanced magnetic resonance generally corresponding to the formula Y-L-R, wherein Y represents a catalyst-binding moiety having at least one isotopically labeled heteroatom, L represents a cleavable bond, and R represents a hyperpolarized payload having at least one isotopically labeled carbon. Also disclosed herein is a method of cleaving the cleavable agent for enhanced magnetic resonance.

1 . A method of cleaving a cleavable agent for enhanced magnetic resonance, wherein the cleavable agent is of formula:
   Y-L-R   
       wherein Y is a catalyst-binding moiety, L is a cleavable bond, and R is a hyperpolarized payload; wherein Y contains at least one isotopically labeled heteroatom and R contains at least one isotopically labeled carbon, and wherein the method comprises:
 hyperpolarizing the cleavable agent via SABRE within a magnetic shield; and 
 depressurizing a container containing the hyperpolarized cleavable agent to cause rapid hydrolytic, aminolytic, or enzymatic cleavage of the bond between the catalyst-binding moiety and the hyperpolarized payload. 
 
     
     
         2 . The method of  claim 1 , wherein Y is bound to a SABRE catalyst. 
     
     
         3 . The method of  claim 2 , wherein the SABRE catalyst is an iridium-type catalyst. 
     
     
         4 . The method of  claim 1 , wherein Y contains at least one isotopically labeled nitrogen. 
     
     
         5 . The method of  claim 1 , wherein R comprises a carboxylic acid or carboxylate thereof, urea, an amino acid, a molecule involved in lipid metabolism, a neurotransmitter, a sugar, a nucleic acid, a drug, a metabolite, or another molecule that binds to or is a substrate of enzymes or other proteins or biomacromolecules. 
     
     
         6 . The method of  claim 5 , wherein R comprises a carboxylic acid or carboxylate thereof involved in a metabolic cycle, an amino acid selected from the group consisting of alanine, glutamine, and arginine, choline or a derivative thereof, glucose, or fructose. 
     
     
         7 . The method of  claim 5 , wherein R is a carboxylic acid or a carboxylate thereof. 
     
     
         8 . The method of  claim 5 , wherein R is an amino acid. 
     
     
         9 . The method of  claim 1 , wherein the cleavable agent corresponds in structure to Formula I, Formula II, Formula III, Formula IV, Formula V, Formula VI, Formula VII, Formula VIII, or Formula IX: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       wherein:
 R 1  is a bond or optionally substituted alkylene; 
 R 2  is optionally substituted alkylene carboxylate or alkyl; and 
 R 3  is optionally substituted alkyl, alkenyl, heteroaryl, haloalkyl, guanidine, alkylene carboxylate, alkenylene carboxylate, or R 3  corresponds in structure to: 
 
       
         
           
           
               
               
           
         
         R 4 , R 5 , R 6 , R 7  or Ware independently selected from the group consisting of hydrogen and optionally substituted alkyl, alkenyl, heteroaryl, haloalkyl, guanidine, alkylene carboxylate, alkenylene carboxylate; 
         wherein at least one nitrogen is  15 N labeled and at least one carbon on R 1 , R 2 , or R 3  is  13 C labeled. 
       
     
     
         10 . The method of  claim 9 , wherein R 1  is methylene. 
     
     
         11 . The method of  claim 9 , wherein R 1  is a bond. 
     
     
         12 . The method of  claim 9 , wherein R 2  is methyl or C(O)OH. 
     
     
         13 . The method of  claim 9 , wherein R 3  is methyl, ethenyl, pyridyl, CF 3 , guanidine, or acrylic carboxylate. 
     
     
         14 . A method of cleaving a cleavable agent for enhanced magnetic resonance, the method comprising:
 hyperpolarizing the cleavable agent via SABRE within a magnetic shield; and   depressurizing a container containing the hyperpolarized cleavable agent to cause rapid hydrolytic, aminolytic, or enzymatic cleavage of the bond between the catalyst-binding moiety and the hyperpolarized payload;   wherein the cleavable agent is selected from the group consisting of:   
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein at least one nitrogen is  15 N labeled and at least one acyclic carbon is  13 C labeled.