Synthesis of nitrodibenzylfuran chromophore for photodeprotection of organic molecules

Abstract

Inventors have developed a chromophore (nitrodibenzylfuranyl, or NBDF) for ultra efficient uncaging of a caged substrate (e.g., an organic molecule such as, for example, an amino acid, a biological molecules, such as, for example, second messengers inside cells). Photolysis of a NBDF derivative of EGTA (i.e. caged calcium) is about 50 times more efficient than others calcium cages (the quantum yield of photolysis is 0.6 and the extinction coefficient is 18,400. NDBF-EGTA has a 2-photon cross section of about 0.3-0.6 GM).

1 . A photolabile compound comprising a chromophore having a structure based on a three ring fusion wherein two rings are benzyl rings one of which has a nitro group in a 3-position and wherein the two benzyl rings are fused with a heterocycle having 4 carbons and a heteroatom. 
     
     
         2 . The photolabile compound of  claim 1 , wherein the heteroatom is nitrogen or oxygen. 
     
     
         3 . The photolabile compound of  claim 1 , wherein the chromophore is depicted by the formula: 
       
         
           
           
               
               
           
         
       
     
     
         4 . The photolabile compound of  claim 1 , wherein the chromophore is depicted by the formula: 
       
         
           
           
               
               
           
         
       
       wherein Y═H, OMe, OEt, OPr, O(CH 2 ) n CO 2 H, (CH 2 ) n CO 2 H and Z═H, OMe, OEt, OPr, O(CH 2 ) n CO 2 H, (CH 2 ) n CO 2 H; or 
       
         
           
           
               
               
           
         
       
       wherein Y and Z are as defined above, and W═H, Me, Et, Pr, CO 2 H, (CH 2 ) n CO 2 H, CH 2 , CHMe, CMe 2 , (CH 2 ) n PO 3 H 2 , (CH 2 ) n SO 3 H. 
     
     
         5 . The photolabile compound of  claim 2 , further comprising a functional group suitable for covalent or ionic binding of an effector wherein the functional group is bound to the chromophore to form a functionalized chromophore. 
     
     
         6 . The photolabile compound of  claim 3 , further comprising an effector to form a caged compound, wherein the effector is a member selected from the group consisting of a bioactive molecule, a multivalent cation, a fluorophore, biotin, and a crosslinker. 
     
     
         7 . The photolabile compound of  claim 6 , wherein the biomolecule is at least one of amino acids, peptides, proteins, calcium mobilizing agents (IP2, IP3, IP4, IPS, IP6, PIP2, cyclic-ADPribose, sphingosine-1-phosphate, sphingosine, NAADP, diacylglycerol), neurotransmitters, arachidonic acid, sugars, nucleotides and nucleosides and adrenergic agonists. 
     
     
         8 . The photolabile compound of  claim 6 , wherein the multivalent cation is a member selected from the group consisting of Ca +2  and Mg +2 . 
     
     
         9 . The photolabile compound of  claim 6 , wherein the caged compound is an EDTA derivative or an EGTA derivative. 
     
     
         10 . The photolabile compound of  claim 6 , wherein the effector molecule is an amino acid. 
     
     
         11 . The photolabile compound of  claim 10 , wherein the amino acid is a neuroactive amino acid. 
     
     
         12 . The photolabile compound of  claim 11 , wherein the neuroactive amino acid is glutamate or gama-aminobutyric acid. 
     
     
         13 . The photolabile compound of  claim 10 , wherein the chromophore is nitrodibenzylfuran or nitrocarbazole. 
     
     
         14 . The photolabile compound of  claim 1 , wherein the chromophore is depicted by at least one of the following formulas: 
       
         
           
           
               
               
           
         
       
     
     
         15 . The photolabile compound of  claim 6 , wherein the caged compound is: 
       
         
           
           
               
               
           
         
       
     
     
         16 . A caged compound as depicted by at least one of the following formulas: 
       
         
           
           
               
               
           
         
       
       or a derivative thereof having at least one hydrogen substituted by OMe, OEt, OPr, O(CH 2 ) n CO 2 H, or (CH 2 ) n CO 2 H and wherein V is an amino acid. 
     
     
         17 . A caged compound as depicted by at least one of the following formulas: 
       
         
           
           
               
               
           
         
       
       wherein W═H, Me, Et, Pr, CO 2 H, (CH 2 ) n CO 2 H, CH 2 , CHMe, CMe 2 , (CH 2 ) n PO 3 H 2 , (CH 2 ) n SO 3 H; R═H, OMe, OEt, OPr, O(CH 2 ) n CO 2 H, (CH 2 ) n CO 2 H, (CH 2 ) n PO 3 H 2  and n is 0 to 10; 
       
         
           
           
               
               
           
         
         or a derivative thereof having at least one hydrogen substituted by OMe, OEt, OPr, O(CH 2 ) n CO 2 H, or (CH 2 ) n CO 2 H and n=0-10 and wherein X is an effector, said effector is a member selected from the group consisting of a bioactive molecule, a multivalent cation, a fluorophore, biotin, and a crosslinker. 
       
     
     
         18 . A method of photochemical release an effector molecule from a caged compound, the method comprising:
 (a) preparing a caged compound comprising a chromophore of  claim 1 ; and   (b) photolyzing the caged compound with light to release the effector molecule, wherein the effector molecule is selected from gamma-aminobutyric acid and glutamate and wherein the caged compound comprises at least one structure depicted by at least one of the formulas (I)-(XXIX).