US2004137638A1PendingUtilityA1

Chromatography of metal complexes

42
Priority: Mar 4, 2002Filed: Mar 4, 2002Published: Jul 15, 2004
Est. expiryMar 4, 2022(expired)· nominal 20-yr term from priority
Inventors:Urszula SlomczynskaBobby N. TrawickDennis P. RileyArati Naik
B01D 15/3828G01N 30/96G01N 30/74B01D 15/3833G01N 30/02G01N 2030/027G01N 30/50
42
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Claims

Abstract

A high performance liquid chromatography method to routinely and reproducibly detect and quantitate metal complexes. The method comprises loading a solution containing metal complexes onto a column, eluting the metal complex from the column with a mobile phase, the mobile phase comprising an excess of a salt of a coordinating anion in a solvent system, and detecting the metal complex with a detector. Eluting the complex from the column with the mobile phase generates a metal complex in which the coordinating anion (which is a competent ligand) out-competes all other potential ligands present for the available coordination sites on the metal. The metal complexes used in the method of the invention can be different metal complexes, or they can be stereoisomers of the same metal complexes. The high performance liquid chromatography method of the present invention is suitable for the separation of diastereomers of the same metal complexes. Also provided is a chiral high performance liquid chromatography method to separate enantiomers of metal complexes. In this chiral high performance liquid chromatography method a chiral column is employed to achieve the separation of the enantiomers of metal complexes.

Claims

exact text as granted — not AI-modified
What is claimed is:  
     
         1 . A high performance liquid chromatography method comprising: 
 loading a solution containing metal complexes onto a column, wherein the metal complexes are selected from a group consisting of superoxide dismutase mimetic compounds, MRI imaging enhancement agents, catalase mimics, and peroxynitrite decomposition catalysts,    eluting the metal complexes from the column with a mobile phase, said mobile phase comprising an excess of a salt of a coordinating anion in a solvent system, and    detecting the metal complexes with a detector.    
     
     
         2 . The method of  claim 1  wherein the metal complexes comprise superoxide dismutase mimetic compounds.  
     
     
         3 . The method of  claim 1  wherein the metal complexes comprise different metal complexes.  
     
     
         4 . The method of  claim 1  wherein the metal complexes comprise stereoisomers of the same metal complex.  
     
     
         5 . The method of  claim 1  wherein the metal complexes comprise diastereomers of the same metal complex.  
     
     
         6 . The method of  claim 1  wherein the metal complexes comprise enantiomers of the same metal complex.  
     
     
         7 . The method of  claim 1  wherein the metal complexes comprise products of a reaction stream.  
     
     
         8 . The method of  claim 1  wherein the metal complexes are selected from a group consisting of Fe III (salen) complexes, Fe II (1,4,7,10,13-pentaazacyclopentadecane) derivatives, Fe III (porphyrinato) complexes, Mn III (porphyrinato) complexes, M(salen) complexes, and Mn II (1,4,7,10,13-pentaazacyclopentadecane) complexes.  
     
     
         9 . The method of  claim 1  wherein the metal complexes are selected from a group consisting of Mn III (porphyrinato) complexes, Mn III (salen) complexes, and Mn II (1,4,7,10,13-pentaazacyclopentadecane) complexes.  
     
     
         10 . The method of  claim 1  wherein the metal complexes comprise Mn II (1,4,7,10,13-pentaazacyclopentadecane) complexes.  
     
     
         11 . The method of  claim 1  wherein the metal complexes comprise stereoisomers of a Mn II (1,4,7,10,13-pentaazacyclopentadecane) complex.  
     
     
         12 . The method of  claim 1  wherein the metal complexes comprise stereoisomers of a metal complex having the following structure:  
       
         
           
           
               
               
           
         
       
     
     
         13 . The method of  claim 1  wherein the metal complexes comprise diastereomers of a Mn II (1,4,7,10,13-pentaazacyclopentadecane)complex.  
     
     
         14 . The method of  claim 1  wherein the metal complexes comprise enantiomers of a Mn II (1,4,7,10,13-pentaazacyclopentadecane)complex.  
     
     
         15 . The method of  claim 14  wherein the enantiomers are selected from the following structures:  
       
         
           
           
               
               
           
         
       
     
     
         16 . The method of  claim 1  wherein the coordinating anions comprise chloride anions, thiocyanate anions, stearate anions, acetate anions, trifluoroacetate anions, carboxylate anions, formate anions or azide anions.  
     
     
         17 . The method of  claim 1  wherein the salt comprises sodium chloride, lithium chloride, potassium chloride, ammonium chloride, tetrabutylammonium chloride, sodium thiocyanate, potassium thiocyanate, ammonium thiocyanate, lithium thiocyanate, potassium acetate, sodium acetate, ammonium acetate, ammonium trifluoroacetate, lithium acetate, potassium formate, sodium formate, ammonium formate, lithium formate, sodium cyanate, potassium cyanate, ammonium cyanate, potassium carboxylate, sodium carboxylate, lithium stearate, sodium stearate, sodium azide, potassium azide or lithium azide.  
     
     
         18 . The method of  claim 1  wherein the salt comprises sodium chloride, lithium chloride or tetrabutylammonium chloride.  
     
     
         19 . The method of  claim 1  wherein the salt comprises ammonium thiocyanate, sodium thiocyanate or potassium thiocyanate.  
     
     
         20 . The method of  claim 1  wherein the salt comprises a mixture of salts.  
     
     
         21 . The method of  claim 20  wherein the mixture of salts comprises two or more of sodium chloride, lithium chloride, potassium chloride, ammonium chloride, tetrabutylammonium chloride, sodium thiocyanate, potassium thiocyanate, ammonium thiocyanate, lithium thiocyanate, potassium acetate, sodium acetate, ammonium acetate, ammonium trifluoroacetate, lithium acetate, potassium formate, sodium formate, ammonium formate, lithium formate, sodium cyanate, potassium cyanate, ammonium cyanate, potassium carboxylate, sodium carboxylate, lithium stearate, sodium stearate, sodium azide, potassium azide, or lithium azide.  
     
     
         22 . The method of  claim 1  wherein the solvent system comprises a solvent.  
     
     
         23 . The method of  claim 22  wherein the solvent comprises acetonitrile, dioxane, ethanol, methanol, isopropanol, tetrahydrofuran, or water.  
     
     
         24 . The method of  claim 1  wherein the solvent system comprises a mixture of solvents.  
     
     
         25 . The method of  claim 24  wherein the mixture of solvents comprises two or more of acetonitrile, dioxane, ethanol, methanol, isopropanol, tetrahydrofuran, and water.  
     
     
         26 . The method of  claim 25  wherein the solvents comprise acetonitrile and water.  
     
     
         27 . The method of  claim 25  wherein the solvents comprise methanol and water.  
     
     
         28 . The method of  claim 1  wherein the salt is present in the mobile phase at a concentration of between about 0.004 M to about 6 M.  
     
     
         29 . The method of  claim 1  wherein the salt is present in the mobile phase at a concentration of between about 0.1 M to about 1 M.  
     
     
         30 . The method of  claim 1  wherein the salt is present in the mobile phase at a concentration of between about 0.15 M to about 0.6 M.  
     
     
         31 . The method of  claim 18  wherein the sodium chloride is present in the mobile phase at a concentration of between about 0.1 M to about 1 M.  
     
     
         32 . The method of  claim 18  wherein the sodium chloride is present in the mobile phase at a concentration of between about 0.3 M to about 0.7 M.  
     
     
         33 . The method of  claim 18  wherein the sodium chloride is present in the mobile phase at a concentration of between about 0.4 M to about 0.6 M.  
     
     
         34 . The method of  claim 18  wherein the tetrabutylammonium chloride is present in the mobile phase at a concentration of between about 0.005 M to about 0.15 M.  
     
     
         35 . The method of  claim 18  wherein the tetrabutylammonium chloride is present in the mobile phase at a concentration of between about 0.01 M to about 0.13 M.  
     
     
         36 . The method of  claim 18  wherein the tetrabutylammonium chloride is present in the mobile phase at a concentration of between about 0.05 M to about 0.125 M.  
     
     
         37 . The method of  claim 1  wherein the mobile phase comprises acetonitrile in water containing between about 0.1 M to about 0.7 M of salt.  
     
     
         38 . The method of  claim 1  wherein the mobile phase comprises methanol in water containing between about 0.15 M to about 0.6 M of salt.  
     
     
         39 . The method of  claim 1  wherein the mobile phase comprises acetonitrile containing between about 0.3 M to about 0.7 M of sodium chloride.  
     
     
         40 . The method of  claim 1  wherein the mobile phase comprises 5-15% acetonitrile in water containing between about 0.01 M to about 0.13 M of tetrabutylammonium chloride.  
     
     
         41 . The method of  claim 1  wherein the mobile phase comprises 5-15% acetonitrile in water containing between about 0.01 M to about 0.13 M of tetrabutylammonium chloride and between about 0.3 M to about 0.7 M lithium chloride.  
     
     
         42 . The method of  claim 1  wherein the mobile phase comprises 5-10% acetonitrile in water containing between about 0.4 M to about 0.6 M of sodium chloride.  
     
     
         43 . The method of  claim 1  wherein the mobile phase comprises 5-10% acetonitrile in water containing between about 0.05 M to about 0.125 M of tetrabutylammonium chloride.  
     
     
         44 . The method of  claim 1  wherein the mobile phase comprises 5-10% acetonitrile in water containing between about 0.05 M to about 0.125 M of tetrabutylammonium chloride and between about 0.4 M to about 0.6 M lithium chloride.  
     
     
         45 . The method of  claim 1  wherein the mobile phase comprises 1-5% methanol in water containing between about 0.1 M to about 2.5 M of ammonium thiocyanate.  
     
     
         46 . The method of  claim 1  wherein the mobile phase comprises 1-5% methanol in water containing between about 0.05 M to about 0.3 M of tetrabutylammonium chloride.  
     
     
         47 . The method of  claim 1  wherein the mobile phase comprises 1-5% methanol in water containing between about 0.2 M to about 0.3 M of ammonium thiocyanate.  
     
     
         48 . The method of  claim 1  wherein the mobile phase comprises 1-5% methanol in water containing between about 0.05 M to about 0.15 M of tetrabutylammonium chloride.  
     
     
         49 . The method of  claim 1  wherein the column is selected from the group consisting of a C1 modified column, a C3 modified column, a C4 modified column, an octyl (C8) modified column, an octadecyl (C18) modified column, a C18 polymer column, a phenyl column, and an amino-cyano column.  
     
     
         50 . The method of  claim 1  wherein the column is selected from the group consisting of an octadecyl column, a phenyl column, and an amino-cyano column.  
     
     
         51 . The method of  claim 1  wherein the column comprises an octadecyl column.  
     
     
         52 . The method of  claim 51  wherein the octadecyl column comprises a YMC ODS-AQ S5 column®, a Vydac column®, or a Symmetry Shield RP 18  column®.  
     
     
         53 . The method of  claim 1  wherein the column comprises a chiral column.  
     
     
         54 . The method of  claim 53  wherein the chiral column comprises a cellulose column or a Pirkle column.  
     
     
         55 . The method of  claim 54  wherein the cellulose column comprises a Chiralcel-OD-RH column®.  
     
     
         56 . The method of  claim 1  wherein the detector comprises a UV detector.  
     
     
         57 . A high performance liquid chromatography method comprising: 
 loading a solution containing metal complexes onto a column, wherein the metal complexes are selected from a group consisting of superoxide dismutase mimetic compounds, MRI imaging enhancement agents, catalase mimics, and peroxynitrite decomposition catalysts,    eluting the metal complexes from the column with a mobile phase, said mobile phase comprising an excess of a salt of a coordinating anion in a solvent system, wherein eluting with said mobile phase drives the substantial formation of metal complexes containing the coordinating anion as ligands, and    detecting the metal complexes with a detector.    
     
     
         58 . The method of  claim 57  wherein the metal complexes comprise superoxide dismutase mimetic compounds.  
     
     
         59 . The method of  claim 57  wherein the metal complexes are selected from a group consisting of Fe III (salen) complexes, Fe II (1,4,7,10,13-pentaazacyclopentadecane) derivatives, Fe III (porphyrinato) complexes, Mn III (porphyrinato) complexes, M III (salen) complexes, and Mn II (1,4,7,10,13-pentaazacyclopentadecane) complexes.  
     
     
         60 . The method of  claim 57  wherein the metal complexes comprise Mn II (1,4,7,10,13-pentaazacyclopentadecane) complexes.  
     
     
         61 . The method of  claim 57  wherein the metal complexes comprise stereoisomers of a Mn II (1,4,7,10,13-pentaazacyclopentadecane) complex.  
     
     
         62 . The method of  claim 57  wherein the metal complexes comprise stereoisomers of a metal complex having the following structure:  
       
         
           
           
               
               
           
         
       
     
     
         63 . The method of  claim 57  wherein the salt comprises sodium chloride, lithium chloride, potassium chloride, ammonium chloride, tetrabutylammonium chloride, sodium thiocyanate, potassium thiocyanate, ammonium thiocyanate, lithium thiocyanate, potassium acetate, sodium acetate, ammonium acetate, ammonium trifluoroacetate, lithium acetate, potassium formate, sodium formate, ammonium formate, lithium formate, sodium cyanate, potassium cyanate, ammonium cyanate, potassium carboxylate, sodium carboxylate, lithium stearate, sodium stearate, sodium azide, potassium azide, or lithium azide.  
     
     
         64 . The method of  claim 57  wherein the salt comprises sodium chloride, lithium chloride or tetrabutylammonium chloride, ammonium thiocyanate or potassium thiocyanate.  
     
     
         65 . The method of  claim 57  wherein the salt is present in the mobile phase at a concentration of between about 0.1 M to about 1 M.  
     
     
         66 . The method of  claim 57  wherein the salt is present in the mobile phase at a concentration of between about 0.15 M to about 0.6 M.  
     
     
         67 . The method of  claim 57  wherein the column comprises a chiral column.  
     
     
         68 . A high performance liquid chromatography method comprising: 
 loading a solution containing metal complexes onto a column, wherein the metal complexes are selected from a group consisting of manganese complexes and iron complexes,    eluting the metal complexes from the column with a mobile phase, said mobile phase comprising an excess of a salt of a coordinating anion in a solvent system, and    detecting the metal complexes with a detector.    
     
     
         69 . The method of  claim 68  wherein the metal complexes are selected from a group consisting of superoxide dismutase mimetic compounds, MRI imaging enhancement agents, catalase mimics, and peroxynitrite decomposition catalysts.  
     
     
         70 . The method of  claim 68  wherein the metal complexes comprise superoxide dismutase mimetic compounds.  
     
     
         71 . The method of  claim 68  wherein the metal complexes are selected from a group consisting of Fe II (salen) complexes, Fe III (1,4,7,10,13-pentaazacyclopentadecane) derivatives, Fe II (porphyrinato) complexes, Mn III (porphyrinato) complexes, Mn III (salen) complexes, and Mn II (1,4,7,10,13-pentaazacyclopentadecane) complexes.  
     
     
         72 . The method of  claim 68  wherein the metal complexes are selected from a group consisting of Mn III (porphyrinato) complexes, Mn III (salen) complexes, and Mn II (1,4,7,10,13-pentaazacyclopentadecane) complexes.  
     
     
         73 . The method of  claim 68  wherein the metal complexes comprise Mn II (1,4,7,10,13-pentaazacyclopentadecane) complexes.  
     
     
         74 . The method of  claim 68  wherein the metal complexes comprise stereoisomers of a Mn II (1,4,7,10,13-pentaazacyclopentadecane) complex.  
     
     
         75 . The method of  claim 68  wherein the metal complexes comprise stereoisomers of a metal complex having the following structure:  
       
         
           
           
               
               
           
         
       
     
     
         76 . The method of  claim 68  wherein the salt comprises sodium chloride, lithium chloride, potassium chloride, ammonium chloride, tetrabutylammonium chloride, sodium thiocyanate, potassium thiocyanate, ammonium thiocyanate, lithium thiocyanate, potassium acetate, sodium acetate, ammonium acetate, ammonium trifluoroacetate, lithium acetate, potassium formate, sodium formate, ammonium formate, lithium formate, sodium cyanate, potassium cyanate, ammonium cyanate, potassium carboxylate, sodium carboxylate, lithium stearate, sodium stearate, sodium azide, potassium azide, or lithium azide.  
     
     
         77 . The method of  claim 68  wherein the salt comprises sodium chloride, lithium chloride, tetrabutylammonium chloride, sodium thiocyanate or potassium thiocyanate.  
     
     
         78 . The method of  claim 68  wherein the salt is present in the mobile phase at a concentration of between about 0.1 M to about 1.0 M.  
     
     
         79 . The method of  claim 68  wherein the salt is present in the mobile phase at a concentration of between about 0.15 M to about 0.6 M.  
     
     
         80 . A high performance liquid chromatography method for the analysis of metal complexes comprising: 
 combining metal complexes with an excess of a salt of a coordinating anion in an aqueous solution,    loading a solution containing the metal complexes onto a column,    eluting the metal complexes from the column with a mobile phase, said mobile phase comprising an excess of a salt of a coordinating anion in a solvent system, and    detecting the metal complexes with a detector.    
     
     
         81 . The method of  claim 80  wherein the salt comprises sodium chloride, lithium chloride, potassium chloride, ammonium chloride, tetrabutylammonium chloride, sodium thiocyanate, potassium thiocyanate, ammonium thiocyanate, lithium thiocyanate, potassium acetate, sodium acetate, ammonium acetate, ammonium trifluoroacetate, lithium acetate, potassium formate, sodium formate, ammonium formate, lithium formate, sodium cyanate, potassium cyanate, ammonium cyanate, potassium carboxylate, sodium carboxylate, lithium stearate, sodium stearate, sodium azide, potassium azide, or lithium azide.  
     
     
         82 . The method of  claim 80  wherein the salt comprises sodium thiocyanate, potassium thiocyanate, ammonium thiocyanate, or lithium thiocyanate.  
     
     
         83 . The method of  claim 80  wherein the metal complexes are selected from a group consisting of superoxide dismutase mimetic compounds, catalase mimics, peroxynitrite decomposition catalysts, and MRI imaging agents.  
     
     
         84 . The method of  claim 80  wherein the metal complexes comprise superoxide dismutase mimetic compounds.  
     
     
         85 . The method of  claim 80  wherein the metal complexes are selected from a group consisting of Fe III (salen) complexes, Fe III (1,4,7,10,13-pentaazacyclopentadecane) derivatives, Fe II (porphyrinato) complexes, Mn II (porphyrinato) complexes, Mn III (salen) complexes, and Mn II (1,4,7,10,13-pentaazacyclopentadecane) complexes.  
     
     
         86 . The method of  claim 80  wherein the metal complexes comprise Mn II (1,4,7,10,13-pentaazacyclopentadecane) complexes.  
     
     
         87 . A high performance liquid chromatography method comprising: 
 loading a solution containing metal complexes onto a column,    eluting the metal complexes from the column with a mobile phase, said mobile phase comprising an excess of a salt of a coordinating anion in a solvent system, wherein eluting with said mobile phase drives the formation of metal complexes containing the coordinating anion as ligands, and    detecting the metal complexes with a detector.    
     
     
         88 . The method of  claim 87  wherein the metal complexes are selected from the group consisting of superoxide dismutase mimetic compounds, MRI imaging enhancement agents, catalase mimics, and peroxynitrite decomposition catalysts.  
     
     
         89 . The method of  claim 87  wherein the metal complexes are selected from a group consisting of Fe III (salen) complexes, Fe II (1,4,7,10,13-pentaazacyclopentadecane) derivatives, Fe III (porphyrinato) complexes, Mn III (porphyrinato) complexes, Mn III (salen) complexes, and Mn II (1,4,7,10,13-pentaazacyclopentadecane) complexes.  
     
     
         90 . The method of  claim 87  wherein the metal complexes have the following structure:

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