Methods of treating oral mucositis

Abstract

Methods and kits for treating oral mucositis are disclosed. The treatment comprises administering to a patient in need thereof a Reactive Oxygen Species scavenger in a pharmaceutically acceptable formulation.

What is claimed is: 
     
         1 . A method of treating an oral mucositis in a subject, the method comprising administering a superoxide dismutase mimetic to a subject in need thereof. 
     
     
         2 . A method of treating an oral mucositis in accordance with  claim 1 , wherein the administering lessens the severity of the oral mucositis in a subject. 
     
     
         3 . A method of treating an oral mucositis in accordance with  claim 1 , wherein the superoxide dismutase mimetic is a compound represented by the formula: 
       
         
           
           
               
               
           
         
       
       wherein R 1 , R′ 1 , R 2 , R′ 2 , R 3 , R′ 3 , R 4 , R′ 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R′ 7 , R 8 , R′ 8 , R 9 , R′ 9 , R 10 , and R′ 10  are each independently selected from the group consisting of hydrogen, alkenyl, alkenylcycloalkenyl, alkenylcycloalkyl, alkyl, alkylcycloalkenyl, alkylcycloalkyl, alkynyl, aralkyl, aryl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylcycloalkyl, cycloalkenylalkyl, and heterocyclyl, and aralkyl radicals and radicals attached to the α-carbon or α-amino acids, and —OR 11 , —NR 11 R 12 , —COR 11 , —CO 2 R 11 , —CONR 11 R 12 , —SR 11 , —SOR 11 , —SO 2 R 11 , —SO 2 NR 11 R 12 , —N(OR 11 )(R 12 ), —P(O)(OR 11 )(OR 12 ), —P(O)(OR 11 )(R 12 ), —OP(O)(OR 11 )(OR 12 ), and substituents attached to the α-carbon of α-amino acids, wherein R 11  and R 12  are independently hydrogen or alkyl;
 and optionally, one or more of R 1  or R′ 1  and R 2  or R′ 2 , R 3  or R′ 3  and R 4  or R′ 4 , R 5  or R′ 5  and R 6  or R′ 6 , R 7  or R′ 7  and R 8  or R′ 8 , R 9  or R′ 9  and R 10  or R′ 10  together with the carbon atoms to which they are attached independently form a substituted or unsubstituted and saturated, partially saturated, or unsaturated cycle or heterocycle having 3 to 20 carbon atoms; 
 and optionally, one or more of R 1  and R′ 1 , R 2  and R′ 2 , R 3  and R′ 3 , R 4  and R′ 4 , R 5  and R′ 5 , R 6  and R′ 6 , R 7  and R′ 7 , R 8  and R′ 8 , R 9  and R′ 9 , and R 10  and R′ 10 , together with the carbon atom to which they are attached independently form a substituted or unsubstituted and saturated, partially saturated, or unsaturated cycle or heterocycle having 3 to 20 carbon atoms; 
 and optionally, one or more of R 10  or R′ 10  and R 1  or R′ 1 , R 2  or R′ 2  and R 3  or R′ 3 , R 4  or R′ 4  and R 5  or R′ 5 , R 6  or R′ 6  and R 7  or R′ 7 , or R 8  or R′ 8  and R 9  or R′ 9  together with the carbon atoms to which they are attached independently form a substituted or unsubstituted nitrogen containing heterocycle having 3 to 20 carbon atoms, which may be an aromatic heterocycle in which case the hydrogen attached to the nitrogen which is both part of the heterocycle and the macrocycle and the R groups attached to the carbon atoms which are both part of the heterocycle and the macrocycle are absent; 
 and optionally, one or more of R 1 , R′ 1 , R 2 , R′ 2 , R 3 , R′ 3 , R 4 , R′ 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R′ 7 , R 8 , R′ 8 , R 9 , R′ 9 , R 10 , and R′ 10 , together with a different one of R 1 , R′ 1 , R 2 , R′ 2 , R 3 , R′ 3 , R 4 , R′ 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R′ 7 , R 8 , R′ 8 , R 9 , R′ 9 , R 10 , and R′ 10 , which is attached to a different carbon atom in the macrocyclic ligand may be bound to form a strap represented by the formula:
   —(CH 2 ) I -Q-(CH 2 ) J —R—(CH 2 ) K —S—(CH 2 ) L —
 
 
 
       wherein I, J, K and L independently are integers from 0 to 10 and Q, R and S are independently selected from the group consisting of alkenyl, alkenylcycloalkenyl, alkenylcycloalkyl, alkyl, alkylcycloalkenyl, alkylcycloalkyl, alkynyl, aralkyl, aryl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylcycloalkyl, cycloalkenylalkyl, and heterocyclyl, aza, amide, ammonium, oxa, thia, sulfonyl, sulfinyl, sulfonamide, phosphoryl, phosphinyl, phosphino, phosphonium, keto, ester, alcohol, carbamate, urea, thiocarbonyl, borates, boranes, boraza, silyl, siloxy, silaza, and combinations thereof; and combinations of any of the above;
 wherein M is a cation of a transition metal; 
 and wherein X, Y and Z are independently selected from the group consisting of halide, oxo, aquo, hydroxo, alcohol, phenol, dioxygen, peroxo, hydroperoxo, alkylperoxo, arylperoxo, ammonia, alkylamino, arylamino, heterocycloalkyl amino, heterocycloaryl amino, amine oxides, hydrazine, alkyl hydrazine, aryl hydrazine, nitric oxide, cyanide, cyanate, thiocyanate, isocyanate, isothiocyanate, alkyl nitrile, aryl nitrile, alkyl isonitrile, aryl isonitrile, nitrate, nitrite, azido, alkyl sulfonic acid, aryl sulfonic acid, alkyl sulfoxide, aryl sulfoxide, alkyl aryl sulfoxide, alkyl sulfenic acid, aryl sulfenic acid, alkyl sulfinic acid, aryl sulfinic acid, alkyl thiol carboxylic acid, aryl thiol carboxylic acid, alkyl thiol thiocarboxylic acid, aryl thiol thiocarboxylic acid, alkyl carboxylic acid, aryl carboxylic acid, urea, alkyl urea, aryl urea, alkyl aryl urea, thiourea, alkyl thiourea, aryl thiourea, alkyl aryl thiourea, sulfate, sulfite, bisulfate, bisulfite, thiosulfate, thiosulfite, hydrosulfite, alkyl phosphine, aryl phosphine, alkyl phosphine oxide, aryl phosphine oxide, alkyl aryl phosphine oxide, alkyl phosphine sulfide, aryl phosphine sulfide, alkyl aryl phosphine sulfide, alkyl phosphonic acid, aryl phosphonic acid, alkyl phosphinic acid, aryl phosphinic acid, alkyl phosphinous acid, aryl phosphinous acid, phosphate, thiophosphate, phosphite, pyrophosphite, triphosphate, hydrogen phosphate, dihydrogen phosphate, alkyl guanidino, aryl guanidino, alkyl aryl guanidino, alkyl carbamate, aryl carbamate, alkyl aryl carbamate, alkyl thiocarbamate, aryl thiocarbamate, alkylaryl thiocarbamate, alkyl dithiocarbamate, aryl dithiocarbamate, alkylaryl dithiocarbamate, bicarbonate, carbonate, perchlorate, chlorate, chlorite, hypochlorite, perbromate, bromate, bromite, hypobromite, tetrahalomanganate, tetrafluoroborate, hexafluoroantimonate, hypophosphite, iodate, periodate, metaborate, tetraaryl borate, tetra alkyl borate, tartrate, salicylate, succinate, citrate, ascorbate, saccharinate, amino acid, hydroxamic acid, thiotosylate, and anions of ion exchange resins, or the corresponding anions thereof; 
 or X, Y and Z are independently selected from the group consisting of charge-neutralizing anions which are derived from any monodentate or polydentate coordinating ligand and a ligand system and the corresponding anion thereof; 
 or X, Y and Z are independently attached to one or more of R 1 , R′ 1 , R 2 , R′ 2 , R 3 , R′ 3 , R 4 , R′ 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R′ 7 , R 8 , R′ 8 , R 9 , R′ 9 , R 10 , and R′ 10 ; 
 and n is an integer from 0 to 3. 
 
     
     
         4 . A method in accordance with  claim 3 , wherein M is selected from the group consisting of Mn 2+ , Mn 3+ , Mn 4+ , Mn 6+ , Mn 7+ , Fe 2+ , Fe 3+ , Fe 4+ , Fe 6+ , Ni 2+ , Ni 3+ , Cu 1+ , Cu 2+ , V 2+ , V 3+ , V 4+ , or V 5+ . 
     
     
         5 . A method in accordance with  claim 3 , wherein M is selected from the group consisting of Mn 2+ , Mn 3+ , Mn 4+ , Mn 6+ , Mn 7+ , Fe 2+ , Fe 3+ , Fe 4+ , and Fe 6+ . 
     
     
         6 . A method in accordance with  claim 3 , wherein M is Mn 2 . 
     
     
         7 . A method of treating an oral mucositis in accordance with  claim 1 , wherein the superoxide dismutase mimetic is a compound represented by the formula. 
       
         
           
           
               
               
           
         
       
       wherein a nitrogen of the macrocycle and two adjacent carbon atoms to which the nitrogen is attached independently form a substituted or unsubstituted, saturated, partially saturated or unsaturated nitrogen-containing heterocycle W having 2 to 20 carbon atoms, which may be an aromatic heterocycle in which case the hydrogen attached to the nitrogen which is both part of the heterocycle and the macrocycle and the R groups attached to the carbon atoms which are both part of the heterocycle and the macrocycle are absent;
 and wherein R 1 , R′ 1 , R 2 , R′ 2 , R 3 , R′ 3 , R 4 , R′ 4 , R 5 , R′ 5 , R 6 , R′ 6 , Ry, R′ 7 , R 8 , R′ 8 , R 9 , R′ 9 , R 10 , and R′ 10  are each independently selected from the group consisting of hydrogen, alkenyl, alkenylcycloalkenyl, alkenylcycloalkyl, alkyl, alkylcycloalkenyl, alkylcycloalkyl, alkynyl, aralkyl, aryl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylcycloalkyl, cycloalkenylalkyl, and heterocyclyl, and aralkyl radicals and radicals attached to the α-carbon or α-amino acids, and —OR 11 , —NR 11 R 12 , —COR 11 , —CO 2 R 11 , —CONR 11 R 12 , —SR 11 , —SOR 11 , —SO 2 R 11 , —SO 2 NR 11 R 12 , —N(OR 11 )(R 12 ), —P(O)(OR 11 )(OR 12 ), —P(O)(OR 11 )(R 12 ), —OP(O)(OR 11 )(OR 12 ), and substituents attached to the α-carbon of α-amino acids, wherein R11 and R 12  are independently hydrogen or alkyl; 
 and, optionally, one or more of R 1  and R 2  or R′ 2 , R 3  or R′ 3  and R 4  or R′ 4 , R 5  or R′ 5  and R 6  or R′ 6 , R 7  or R′ 7  and R 8  or R′ 8 , R 9  or R′ 9  and R 10  together with the carbon atoms to which they are attached independently form a substituted or unsubstituted and saturated, partially saturated, or unsaturated cycle or heterocycle having 3 to 20 carbon atoms; 
 and, optionally, one or more of R 2  and R′ 2 , R 3  and R′ 3 , R 4  and R′ 4 , R 5  and R′ 5 , R 6  and R′ 6 , R 7  and R′ 7 , R 8  and R′8, and R 9  and R′ 9 , together with the carbon atom to which they are attached independently form a substituted or unsubstituted and saturated, partially saturated, or unsaturated cycle or heterocycle having 3 to 20 carbon atoms; 
 and, optionally, one or more of R 2  or R′ 2  and R 3  or R′ 3 , R 4  or R′ 4  and R 5  or R′ 5 , R 6  or R′ 6  and R 7  or R′ 7 , or R 8  or R′ 8  and R 9  or R′ 9  together with the carbon atoms to which they are attached independently form a substituted or unsubstituted nitrogen containing heterocycle having 3 to 20 carbon atoms, which may be an aromatic heterocycle in which case the hydrogen attached to the nitrogen which is both part of the heterocycle and the macrocycle and the R groups attached to the carbon atoms which are both part of the heterocycle and the macrocycle are absent; 
 and, optionally, one or more of R 1 , R′ 1 , R 2 , R′ 2 , R 3 , R′ 3 , R 4 , R′ 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R′ 7 , R 8 , R′ 8 , R 9 , R′ 9 , and R 10 , together with a different one of R 1 , R′ 1 , R 2 , R′ 2 , R 3 , R′ 3 , R 4 , R′ 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R′ 7 , R 8 , R′ 8 , R 9 , R′ 9 , and R 10 , which is attached to a different carbon atom in the macrocyclic ligand may be bound to form a strap represented by the formula:
   —(CH 2 ) I -Q-(CH 2 ) J —R—(CH 2 ) K —S—(CH 2 ) L —
 
 
 
       wherein I, J, K and L independently are integers from 0 to 10 and Q, R and S are independently selected from the group consisting of alkenyl, alkenylcycloalkenyl, alkenylcycloalkyl, alkyl, alkylcycloalkenyl, alkylcycloalkyl, alkynyl, aralkyl, aryl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylcycloalkyl, cycloalkenylalkyl, and heterocyclyl, aza, amide, ammonium, oxa, thia, sulfonyl, sulfinyl, sulfonamide, phosphoryl, phosphinyl, phosphino, phosphonium, keto, ester, alcohol, carbamate, urea, thiocarbonyl, borates, boranes, boraza, silyl, siloxy, silaza, and combinations thereof; and optionally, one or more of R 1 , R′ 1 , R 2 , R′ 2 , R 3 , R′ 3 , R 4 , R′ 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R′ 7 , R 8 , R′ 8 , R 9 , R′ 9 , and R 10 , may be bound to an atom of heterocycle W to form a strap represented by the formula:
   —(CH 2 ) I -Q-(CH 2 ) J —R—(CH 2 ) K —S—(CH 2 ) L —
 
 
       wherein I, J, K and L independently are integers from 0 to 10 and Q, R and S are independently selected from the group consisting of alkenyl, alkenylcycloalkenyl, alkenylcycloalkyl, alkyl, alkylcycloalkenyl, alkylcycloalkyl, alkynyl, aralkyl, aryl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylcycloalkyl, cycloalkenylalkyl, and heterocyclyl, aza, amide, ammonium, oxa, thia, sulfonyl, sulfinyl, sulfonamide, phosphoryl, phosphinyl, phosphino, phosphonium, keto, ester, alcohol, carbamate, urea, thiocarbonyl, borates, boranes, boraza, silyl, siloxy, silaza, and combinations thereof; and combinations of any of the above;
 wherein M is a cation of a transition metal; 
 and wherein X, Y and Z are independently selected from the group consisting of halide, oxo, aquo, hydroxo, alcohol, phenol, dioxygen, peroxo, hydroperoxo, alkylperoxo, arylperoxo, ammonia, alkylamino, arylamino, heterocycloalkyl amino, heterocycloaryl amino, amine oxides, hydrazine, alkyl hydrazine, aryl hydrazine, nitric oxide, cyanide, cyanate, thiocyanate, isocyanate, isothiocyanate, alkyl nitrile, aryl nitrile, alkyl isonitrile, aryl isonitrile, nitrate, nitrite, azido, alkyl sulfonic acid, aryl sulfonic acid, alkyl sulfoxide, aryl sulfoxide, alkyl aryl sulfoxide, alkyl sulfenic acid, aryl sulfenic acid, alkyl sulfinic acid, aryl sulfinic acid, alkyl thiol carboxylic acid, aryl thiol carboxylic acid, alkyl thiol thiocarboxylic acid, aryl thiol thiocarboxylic acid, alkyl carboxylic acid, aryl carboxylic acid, urea, alkyl urea, aryl urea, alkyl aryl urea, thiourea, alkyl thiourea, aryl thiourea, alkyl aryl thiourea, sulfate, sulfite, bisulfate, bisulfite, thiosulfate, thiosulfite, hydrosulfite, alkyl phosphine, aryl phosphine, alkyl phosphine oxide, aryl phosphine oxide, alkyl aryl phosphine oxide, alkyl phosphine sulfide, aryl phosphine sulfide, alkyl aryl phosphine sulfide, alkyl phosphonic acid, aryl phosphonic acid, alkyl phosphinic acid, aryl phosphinic acid, alkyl phosphinous acid, aryl phosphinous acid, phosphate, thiophosphate, phosphite, pyrophosphite, triphosphate, hydrogen phosphate, dihydrogen phosphate, alkyl guanidino, aryl guanidino, alkyl aryl guanidino, alkyl carbamate, aryl carbamate, alkyl aryl carbamate, alkyl thiocarbamate, aryl thiocarbamate, alkylaryl thiocarbamate, alkyl dithiocarbamate, aryl dithiocarbamate, alkylaryl dithiocarbamate, bicarbonate, carbonate, perchlorate, chlorate, chlorite, hypochlorite, perbromate, bromate, bromite, hypobromite, tetrahalomanganate, tetrafluoroborate, hexafluoroantimonate, hypophosphite, iodate, periodate, metaborate, tetraaryl borate, tetra alkyl borate, tartrate, salicylate, succinate, citrate, ascorbate, saccharinate, amino acid, hydroxamic acid, thiotosylate, and anions of ion exchange resins, or the corresponding anions thereof; 
 or X, Y and Z are independently selected from the group consisting of charge-neutralizing anions which are derived from any monodentate or polydentate coordinating ligand and a ligand system and the corresponding anion thereof; 
 or X, Y and Z are independently attached to one or more of R 1 , R′ 1 , R 2 , R′ 2 , R 3 , R′ 3 , R 4 , R′ 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R′ 7 , R 8 , R′ 8 , R 9 , R′ 9 , and R 10 ; 
 and n is an integer from 0 to 3. 
 
     
     
         8 . A method in accordance with  claim 7 , wherein M is selected from the group consisting of Mn 2+ , Mn 3+ , Mn 4+ , Mn 6+ , Mn 7+ , Fe 2+ , Fe 3+ , Fe 4+ , Fe 6+ , Ni 2+ , Ni 3+ , Cu 1+ , Cu 2+ , V 2+ , V 3+ , V 4+ , and V 5+ . 
     
     
         9 . A method in accordance with  claim 7 , wherein M is selected from the group consisting of Mn 2+ , Mn 3+ , Mn 4+ , Mn 6+ , Mn 7+ , Fe 2+ , Fe 3+ , Fe 4+ , and Fe 6+ . 
     
     
         10 . A method in accordance with  claim 7 , wherein M is Mn 2+ . 
     
     
         11 . A method in accordance with  claim 7 , where W is a substituted or unsubstituted pyridino moiety. 
     
     
         12 . A method of treating an oral mucositis in accordance with  claim 1 , wherein the superoxide dismutase mimetic is a compound represented by the formula: 
       
         
           
           
               
               
           
         
       
       wherein a nitrogen of the macrocycle and two adjacent carbon atoms to which the nitrogen is attached independently form a substituted or unsubstituted, saturated, partially saturated or unsaturated nitrogen-containing heterocycle W having 2 to 20 carbon atoms, which may be an aromatic heterocycle in which case the hydrogen attached to the nitrogen which is both part of the heterocycle and the macrocycle and the R groups attached to the carbon atoms which are both part of the heterocycle and the macrocycle are absent;
 and two sets of two adjacent carbon atoms of the macrocycle independently form substituted or unsubstituted, saturated, partially saturated or unsaturated, cycles or heterocycles U and V having 3 to 20 carbon atoms; 
 and wherein R 1 , R′ 1 , R 2 , R′ 2 , R 3 , R′ 3 , R 4 , R′ 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R′ 7 , R 8 , R′ 8 , R 9 , R′ 9 , R 10 , and R′ 10  are each independently selected from the group consisting of hydrogen, alkenyl, alkenylcycloalkenyl, alkenylcycloalkyl, alkyl, alkylcycloalkenyl, alkylcycloalkyl, alkynyl, aralkyl, aryl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylcycloalkyl, cycloalkenylalkyl, and heterocyclyl, and aralkyl radicals and radicals attached to the α-carbon or α-amino acids, and —OR 11 , —NR 11 R 12 , —COR 11 , —CO 2 R 11 , —CONR 11 R 12 , —SR 11 , —SOR 11 , —SO 2 R 11 , —SO 2 NR 11 R 12 , —N(OR 11 )(R 12 ), —P(O)(OR 11 )(OR 12 ), —P(O)(OR 11 )(R 12 ), —OP(O)(OR 11 )(OR 12 ), and substituents attached to the α-carbon of α-amino acids, wherein R 11  and R 12  are independently hydrogen or alkyl; 
 and, optionally, one or more of R 1  and R 2  or R′ 2 , R 5  or R′ 5  and R 6  or R′ 6 , R 9  or R′ 9  and R 10  together with the carbon atoms to which they are attached independently form a substituted or unsubstituted and saturated, partially saturated, or unsaturated cycle or heterocycle having 3 to 20 carbon atoms; 
 and, optionally, one or more of R 2  and R′ 2 , R 5  and R′ 5 , R 6  and R′ 6 , and R 9  and R′ 9 , together with the carbon atom to which they are attached independently form a substituted or unsubstituted and saturated, partially saturated, or unsaturated cycle or heterocycle having 3 to 20 carbon atoms; 
 and, optionally, one or more of R 2  or R′ 2  and R 3 , R 4  and R 5  or R′ 5 , R 6  or R′ 6  and R 7 , or R 8  and R 9  or R′ 9  together with the carbon atoms to which they are attached independently form a substituted or unsubstituted nitrogen containing heterocycle having 3 to 20 carbon atoms, which may be an aromatic heterocycle in which case the hydrogen attached to the nitrogen which is both part of the heterocycle and the macrocycle and the R groups attached to the carbon atoms which are both part of the heterocycle and the macrocycle are absent; 
 and, optionally, one or more of R 1 , R 2 , R′ 2 , R 3 , R 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R 8 , R 9 , R′ 9 , and R 10 , together with a different one of R 1 , R 2 , R′ 2 , R 3 , R 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R 8 , R 9 , R′ 9 , and R 10 , which is attached to a different carbon atom in the macrocyclic ligand may be bound to form a strap represented by the formula:
   —(CH 2 ) I -Q-(CH 2 ) J —R—(CH 2 ) K —S—(CH 2 ) L —
 
 
 
       wherein
 I, J, K and L independently are integers from 0 to 10 and Q, R and S are independently selected from the group consisting of alkenyl, alkenylcycloalkenyl, alkenylcycloalkyl, alkyl, alkylcycloalkenyl, alkylcycloalkyl, alkynyl, aralkyl, aryl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylcycloalkyl, cycloalkenylalkyl, and heterocyclyl, aza, amide, ammonium, oxa, thia, sulfonyl, sulfinyl, sulfonamide, phosphoryl, phosphinyl, phosphino, phosphonium, keto, ester, alcohol, carbamate, urea, thiocarbonyl, borates, boranes, boraza, silyl, siloxy, silaza, and combinations thereof; and, optionally, one or more of R 1 , R 2 , R′ 2 , R 3 , R 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R 8 , R 9 , R′ 9 , and R 10 , may be individually bound to an atom of heterocycles U, V and W to form a strap represented by the formula:
   —(CH 2 ) I -Q-(CH 2 ) J —R—(CH 2 ) K —S—(CH 2 ) L —
 
 
 
       wherein
 I, J, K and L independently are integers from 0 to 10 and Q, R and S are independently selected from the group consisting of alkenyl, alkenylcycloalkenyl, alkenylcycloalkyl, alkyl, alkylcycloalkenyl, alkylcycloalkyl, alkynyl, aralkyl, aryl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylcycloalkyl, cycloalkenylalkyl, and heterocyclyl, aza, amide, ammonium, oxa, thia, sulfonyl, sulfinyl, sulfonamide, phosphoryl, phosphinyl, phosphino, phosphonium, keto, ester, alcohol, carbamate, urea, thiocarbonyl, borates, boranes, boraza, silyl, siloxy, silaza, and combinations thereof; and combinations of any of the above; 
 wherein M is a cation of a transition metal; 
 and wherein X, Y and Z are independently selected from the group consisting of halide, oxo, aquo, hydroxo, alcohol, phenol, dioxygen, peroxo, hydroperoxo, alkylperoxo, arylperoxo, ammonia, alkylamino, arylamino, heterocycloalkyl amino, heterocycloaryl amino, amine oxides, hydrazine, alkyl hydrazine, aryl hydrazine, nitric oxide, cyanide, cyanate, thiocyanate, isocyanate, isothiocyanate, alkyl nitrile, aryl nitrile, alkyl isonitrile, aryl isonitrile, nitrate, nitrite, azido, alkyl sulfonic acid, aryl sulfonic acid, alkyl sulfoxide, aryl sulfoxide, alkyl aryl sulfoxide, alkyl sulfenic acid, aryl sulfenic acid, alkyl sulfinic acid, aryl sulfinic acid, alkyl thiol carboxylic acid, aryl thiol carboxylic acid, alkyl thiol thiocarboxylic acid, aryl thiol thiocarboxylic acid, alkyl carboxylic acid, aryl carboxylic acid, urea, alkyl urea, aryl urea, alkyl aryl urea, thiourea, alkyl thiourea, aryl thiourea, alkyl aryl thiourea, sulfate, sulfite, bisulfate, bisulfite, thiosulfate, thiosulfite, hydrosulfite, alkyl phosphine, aryl phosphine, alkyl phosphine oxide, aryl phosphine oxide, alkyl aryl phosphine oxide, alkyl phosphine sulfide, aryl phosphine sulfide, alkyl aryl phosphine sulfide, alkyl phosphonic acid, aryl phosphonic acid, alkyl phosphinic acid, aryl phosphinic acid, alkyl phosphinous acid, aryl phosphinous acid, phosphate, thiophosphate, phosphite, pyrophosphite, triphosphate, hydrogen phosphate, dihydrogen phosphate, alkyl guanidino, aryl guanidino, alkyl aryl guanidino, alkyl carbamate, aryl carbamate, alkyl aryl carbamate, alkyl thiocarbamate, aryl thiocarbamate, alkylaryl thiocarbamate, alkyl dithiocarbamate, aryl dithiocarbamate, alkylaryl dithiocarbamate, bicarbonate, carbonate, perchlorate, chlorate, chlorite, hypochlorite, perbromate, bromate, bromite, hypobromite, tetrahalomanganate, tetrafluoroborate, hexafluoroantimonate, hypophosphite, iodate, periodate, metaborate, tetraaryl borate, tetra alkyl borate, tartrate, salicylate, succinate, citrate, ascorbate, saccharinate, amino acid, hydroxamic acid, thiotosylate, and anions of ion exchange resins, or the corresponding anions thereof; 
 or X, Y and Z are independently selected from the group consisting of charge-neutralizing anions which are derived from any monodentate or polydentate coordinating ligand and a ligand system and the corresponding anion thereof; 
 or X, Y and Z are independently attached to one or more of R 1 , R 2 , R′ 2 , R 3 , R 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R 8 , R 9 , R′ 9 , and R 10 ; 
 and n is an integer from 0 to 3. 
 
     
     
         13 . A method in accordance with  claim 12 , wherein M is selected from the group consisting of Mn 2+ , Mn 3+ , Mn 4+ , Mn 6+ , Mn 7+ , Fe 2+ , Fe 3+ , Fe 4+ , Fe 6+ , Ni 2+ , Ni 3+ , Cu 1+ , Cu 2+ , V 2+ , V 3+ , V 4+ , and V 5+ . 
     
     
         14 . A method in accordance with  claim 12 , wherein M is selected from the group consisting of Mn 2+ , Mn 3+ , Mn 4 , Mn 6+ , Mn 7+ , Fe 2+ , Fe 3+ , Fe 4+ , and Fe 6+ . 
     
     
         15 . A method in accordance with  claim 12 , wherein M is Mn 2+ . 
     
     
         16 . A method in accordance with  claim 12 , wherein U and V are saturated cycloalkyl heterocycles having 3 to 20 carbon atoms. 
     
     
         17 . A method in accordance with  claim 12 , wherein U and V are saturated cycloalkyl heterocycles having 4 to 10 carbon atoms. 
     
     
         18 . A method in accordance with  claim 12 , wherein U and V are trans-cyclohexanyl fused rings. 
     
     
         19 . A method in accordance with  claim 12 , wherein W is a substituted or unsubstituted pyridino moiety. 
     
     
         20 . A method in accordance with  claim 12 , wherein U and V are trans-cyclohexanyl fused rings and W is a substituted pyridino moiety. 
     
     
         21 . A method of treating an oral mucositis in accordance with  claim 1 , wherein the superoxide dismutase mimetic is a compound represented by the formula: 
       
         
           
           
               
               
           
         
       
     
     
         22 . A method of treating an oral mucositis in accordance with  claim 1 , wherein the subject is a mammal 
     
     
         23 . A method of treating an oral mucositis in accordance with  claim 22 , wherein the mammal is a human patient in need thereof. 
     
     
         24 . A method of treating an oral mucositis in accordance with  claim 1 , wherein the subject is receiving a cancer treatment. 
     
     
         25 . A method of treating an oral mucositis in accordance with  claim 24 , wherein the cancer treatment comprises chemotherapy. 
     
     
         26 . A method of treating an oral mucositis in accordance with  claim 24 , wherein the cancer treatment comprises radiation therapy. 
     
     
         27 . A method of treating an oral mucositis in accordance with  claim 24 , wherein the administering occurs prior to the subject receiving the cancer treatment. 
     
     
         28 . A method of treating an oral mucositis in accordance with  claim 24 , wherein the administering occurs subsequent to the subject receiving the cancer treatment. 
     
     
         29 . A method of treating an oral mucositis in accordance with  claim 24 , wherein the administering occurs simultaneous with the subject receiving the cancer treatment. 
     
     
         30 . A method of treating a cancer, the method comprising:
 a) administering to a subject in need of cancer treatment a pharmaceutical composition comprising a superoxide dismutase mimetic; and   b) administering to the subject an effective amount of a cancer treatment, whereby the superoxide dismutase mimetic prevents or reduces oral mucositis in the subject.   
     
     
         31 . A method of treating a cancer in accordance with  claim 30 , wherein the cancer treatment comprises radiation therapy. 
     
     
         32 . A method of treating a cancer in accordance with  claim 30 , wherein the cancer treatment comprises chemotherapy. 
     
     
         33 . A method of treating a cancer in accordance with  claim 30 , wherein the superoxide dismutase mimetic is a reactive oxygen species scavenger; and wherein the pharmaceutical composition further comprises at least one additional reactive oxygen species scavenger. 
     
     
         34 . A method of treating a cancer in accordance with  claim 33 , wherein the at least one additional reactive oxygen species scavenger is selected from the group consisting of amifostine and N-acetylcysteine. 
     
     
         35 . A method of treating a cancer in accordance with  claim 30 , wherein the method further comprises administering a pharmaceutical composition which upregulates expression of at least one transcription factor which increases expression of one or more genes controlling at least one naturally occurring antioxidant pathway. 
     
     
         36 . A method of treating a cancer in accordance with  claim 35 , wherein the at least one transcription factor is Nrf-2 
     
     
         37 . A method of treating a cancer in accordance with  claim 35 , wherein the composition which upregulates expression of at least one transcription factor is palifermin 
     
     
         38 . A method of treating a cancer in accordance with  claim 30 , wherein the subject is a mammal 
     
     
         39 . A method of treating cancer in accordance with  claim 30 , wherein the mammal is a human patient in need thereof. 
     
     
         40 . A method of treating cancer in accordance with  claim 30 , wherein the superoxide dismutase mimetic is a compound represented by the formula: 
       
         
           
           
               
               
           
         
       
       wherein R 1 , R′ 1 , R 2 , R′ 2 , R 3 , R′ 3 , R 4 , R′ 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R′ 7 , R 8 , R′ 8 , R 9 , R′ 9 , R 10 , and R′ 10  are each independently selected from the group consisting of hydrogen, alkenyl, alkenylcycloalkenyl, alkenylcycloalkyl, alkyl, alkylcycloalkenyl, alkylcycloalkyl, alkynyl, aralkyl, aryl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylcycloalkyl, cycloalkenylalkyl, and heterocyclyl, and aralkyl radicals and radicals attached to the α-carbon or α-amino acids, and —OR 11 , —NR 11 R 12 , —COR 11 , —CO 2 R 11 , —CONR 11 R 12 , —SR 11 , —SOR 11 , —SO 2 R 11 , —SO 2 NR 11 R 12 , —N(OR 11 )(R 12 ), —P(O)(OR 11 )(OR 12 ), —P(O)(OR 11 )(R 12 ), —OP(O)(OR 11 )(OR 12 ), and substituents attached to the α-carbon of α-amino acids, wherein R 11  and R 12  are independently hydrogen or alkyl;
 and optionally, one or more of R 1  or R′ 1  and R 2  or R′ 2 , R 3  or R′ 3  and R 4  or R′ 4 , R 5  or R′ 5  and R 6  or R′ 6 , R 7  or R′ 7  and R 8  or R′ 8 , R 9  or R′ 9  and R 10  or R′ 10  together with the carbon atoms to which they are attached independently form a substituted or unsubstituted and saturated, partially saturated, or unsaturated cycle or heterocycle having 3 to 20 carbon atoms; 
 and optionally, one or more of R 1  and R′ 1 , R 2  and R′ 2 , R 3  and R′ 3 , R 4  and R′ 4 , R 5  and R′ 5 , R 6  and R′ 6 , R 7  and R′ 7 , R 8  and R′ 8 , R 9  and R′ 9 , and R 10  and R′ 10 , together with the carbon atom to which they are attached independently form a substituted or unsubstituted and saturated, partially saturated, or unsaturated cycle or heterocycle having 3 to 20 carbon atoms; 
 and optionally, one or more of R 10  or R′ 10  and R 1  or R′ 1 , R 2  or R′ 2  and R 3  or R′ 3 , R 4  or R′ 4  and R 5  or R′ 5 , R 6  or R′ 6  and R 7  or R′ 7 , or R a  or R′ 8  and R 9  or R′ 9  together with the carbon atoms to which they are attached independently form a substituted or unsubstituted nitrogen containing heterocycle having 3 to 20 carbon atoms, which may be an aromatic heterocycle in which case the hydrogen attached to the nitrogen which is both part of the heterocycle and the macrocycle and the R groups attached to the carbon atoms which are both part of the heterocycle and the macrocycle are absent; 
 and optionally, one or more of R 1 , R′ 1 , R 2 , R′ 2 , R 3 , R′ 3 , R 4 , R′ 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R′ 7 , R 8 , R′ 8 , R 9 , R′ 9 , R 10 , and R′ 10 , together with a different one of R 1 , R′ 1 , R 2 , R′ 2 , R 3 , R′ 3 , R 4 , R′ 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R′ 7 , R 8 , R′ 8 , R 9 , R′ 9 , R 10 , and R′ 10 , which is attached to a different carbon atom in the macrocyclic ligand may be bound to form a strap represented by the formula:
   —(CH 2 ) I -Q-(CH 2 ) J —R—(CH 2 ) K —S—(CH 2 ) L —
 
 
 
       wherein I, J, K and L independently are integers from 0 to 10 and Q, R and S are independently selected from the group consisting of alkenyl, alkenylcycloalkenyl, alkenylcycloalkyl, alkyl, alkylcycloalkenyl, alkylcycloalkyl, alkynyl, aralkyl, aryl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylcycloalkyl, cycloalkenylalkyl, and heterocyclyl, aza, amide, ammonium, oxa, thia, sulfonyl, sulfinyl, sulfonamide, phosphoryl, phosphinyl, phosphino, phosphonium, keto, ester, alcohol, carbamate, urea, thiocarbonyl, borates, boranes, boraza, silyl, siloxy, silaza, and combinations thereof; and combinations of any of the above;
 wherein M is a cation of a transition metal; 
 and wherein X, Y and Z are independently selected from the group consisting of halide, oxo, aquo, hydroxo, alcohol, phenol, dioxygen, peroxo, hydroperoxo, alkylperoxo, arylperoxo, ammonia, alkylamino, arylamino, heterocycloalkyl amino, heterocycloaryl amino, amine oxides, hydrazine, alkyl hydrazine, aryl hydrazine, nitric oxide, cyanide, cyanate, thiocyanate, isocyanate, isothiocyanate, alkyl nitrile, aryl nitrile, alkyl isonitrile, aryl isonitrile, nitrate, nitrite, azido, alkyl sulfonic acid, aryl sulfonic acid, alkyl sulfoxide, aryl sulfoxide, alkyl aryl sulfoxide, alkyl sulfenic acid, aryl sulfenic acid, alkyl sulfinic acid, aryl sulfinic acid, alkyl thiol carboxylic acid, aryl thiol carboxylic acid, alkyl thiol thiocarboxylic acid, aryl thiol thiocarboxylic acid, alkyl carboxylic acid, aryl carboxylic acid, urea, alkyl urea, aryl urea, alkyl aryl urea, thiourea, alkyl thiourea, aryl thiourea, alkyl aryl thiourea, sulfate, sulfite, bisulfate, bisulfite, thiosulfate, thiosulfite, hydrosulfite, alkyl phosphine, aryl phosphine, alkyl phosphine oxide, aryl phosphine oxide, alkyl aryl phosphine oxide, alkyl phosphine sulfide, aryl phosphine sulfide, alkyl aryl phosphine sulfide, alkyl phosphonic acid, aryl phosphonic acid, alkyl phosphinic acid, aryl phosphinic acid, alkyl phosphinous acid, aryl phosphinous acid, phosphate, thiophosphate, phosphite, pyrophosphite, triphosphate, hydrogen phosphate, dihydrogen phosphate, alkyl guanidino, aryl guanidino, alkyl aryl guanidino, alkyl carbamate, aryl carbamate, alkyl aryl carbamate, alkyl thiocarbamate, aryl thiocarbamate, alkylaryl thiocarbamate, alkyl dithiocarbamate, aryl dithiocarbamate, alkylaryl dithiocarbamate, bicarbonate, carbonate, perchlorate, chlorate, chlorite, hypochlorite, perbromate, bromate, bromite, hypobromite, tetrahalomanganate, tetrafluoroborate, hexafluoroantimonate, hypophosphite, iodate, periodate, metaborate, tetraaryl borate, tetra alkyl borate, tartrate, salicylate, succinate, citrate, ascorbate, saccharinate, amino acid, hydroxamic acid, thiotosylate, and anions of ion exchange resins, or the corresponding anions thereof; 
 or X, Y and Z are independently selected from the group consisting of charge-neutralizing anions which are derived from any monodentate or polydentate coordinating ligand and a ligand system and the corresponding anion thereof; 
 or X, Y and Z are independently attached to one or more of R 1 , R′ 1 , R 2 , R′ 2 , R 3 , R′ 3 , R 4 , R′ 4 , R 5 , R′ 5 , R 6 , R′ 7 , R 7 , R′ 7 , R 8 , R′ 8 , R 9 , R′ 9 , R 10 , and R′ 10 ; 
 and n is an integer from 0 to 3. 
 
     
     
         41 . A method of treating cancer in accordance with  claim 30 , wherein the superoxide dismutase mimetic is a compound represented by the formula: 
       
         
           
           
               
               
           
         
       
       wherein a nitrogen of the macrocycle and two adjacent carbon atoms to which the nitrogen is attached independently form a substituted or unsubstituted, saturated, partially saturated or unsaturated nitrogen-containing heterocycle W having 2 to 20 carbon atoms, which may be an aromatic heterocycle in which case the hydrogen attached to the nitrogen which is both part of the heterocycle and the macrocycle and the R groups attached to the carbon atoms which are both part of the heterocycle and the macrocycle are absent;
 and wherein R 1 , R′ 1 , R 2 , R′ 2 , R 3 , R′ 3 , R 4 , R′ 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R′ 7 , R 8 , R′ 8 , R 9 , R′ 9 , R 10 , and R′ 10  are each independently selected from the group consisting of hydrogen, alkenyl, alkenylcycloalkenyl, alkenylcycloalkyl, alkyl, alkylcycloalkenyl, alkylcycloalkyl, alkynyl, aralkyl, aryl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylcycloalkyl, cycloalkenylalkyl, and heterocyclyl, and aralkyl radicals and radicals attached to the α-carbon or α-amino acids, and —OR 11 , —NR 11 R 12 , —COR 11 , —CO 2 R 11 , —CONR 11 R 12 , —SR 11 , —SOR 11 , —SO 2 R 11 , —SO 2 NR 11 R 12 , —N(OR 11 )(R 12 ), —P(O)(OR 11 )(OR 12 ), —P(O)(OR 1 )(R 12 ), —OP(O)(OR 11 )(OR 12 ), and substituents attached to the α-carbon of α-amino acids, wherein R 11  and R 12  are independently hydrogen or alkyl; 
 and, optionally, one or more of R 1  and R 2  or R′ 2 , R 3  or R′ 3  and R 4  or R′ 4 , R 5  or R′ 5  and R 6  or R′ 6 , R 7  or R′ 7  and R 8  or R′ 8 , R 9  or R′ 9  and R 10  together with the carbon atoms to which they are attached independently form a substituted or unsubstituted and saturated, partially saturated, or unsaturated cycle or heterocycle having 3 to 20 carbon atoms; 
 and, optionally, one or more of R 2  and R′ 2 , R 3  and R′ 3 , R 4  and R′ 4 , R 5  and R′ 5 , R 6  and R′ 6 , R 7  and R′ 7 , R 8  and R′ 8 , and R 9  and R′ 9 , together with the carbon atom to which they are attached independently form a substituted or unsubstituted and saturated, partially saturated, or unsaturated cycle or heterocycle having 3 to 20 carbon atoms; 
 and, optionally, one or more of R 2  or R′ 2  and R 3  or R′ 3 , R 4  or R′ 4  and R 5  or R′ 5 , R 6  or R′ 6  and R 7  or R′ 7 , or R 8  or R′ 8  and R 9  or R′ 9  together with the carbon atoms to which they are attached independently form a substituted or unsubstituted nitrogen containing heterocycle having 3 to 20 carbon atoms, which may be an aromatic heterocycle in which case the hydrogen attached to the nitrogen which is both part of the heterocycle and the macrocycle and the R groups attached to the carbon atoms which are both part of the heterocycle and the macrocycle are absent; 
 and, optionally, one or more of R 1 , R′ 1 , R 2 , R′ 2 , R 3 , R′ 3 , R 4 , R′ 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R′ 7 , R 8 , R′ 8 , R 9 , R′ 9 , and R 10 , together with a different one of R 1 , R′ 1 , R 2 , R′ 2 , R 3 , R′ 3 , R 4 , R′ 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R′ 7 , R 8 , R′ 8 , R 9 , R′ 9 , and R 10 , which is attached to a different carbon atom in the macrocyclic ligand may be bound to form a strap represented by the formula:
   —(CH 2 ) I -Q-(CH 2 ) J —R—(CH 2 ) K —S—(CH 2 ) L —
 
 
 
       wherein I, J, K and L independently are integers from 0 to 10 and Q, R and S are independently selected from the group consisting of alkenyl, alkenylcycloalkenyl, alkenylcycloalkyl, alkyl, alkylcycloalkenyl, alkylcycloalkyl, alkynyl, aralkyl, aryl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylcycloalkyl, cycloalkenylalkyl, and heterocyclyl, aza, amide, ammonium, oxa, thia, sulfonyl, sulfinyl, sulfonamide, phosphoryl, phosphinyl, phosphino, phosphonium, keto, ester, alcohol, carbamate, urea, thiocarbonyl, borates, boranes, boraza, silyl, siloxy, silaza, and combinations thereof; and optionally, one or more of R 1 , R′ 1 , R 2 , R′ 2 , R 3 , R′ 3 , R 4 , R′ 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R′ 7 , R 8 , R′ 8 , R 9 , R′ 9 , and R 10 , may be bound to an atom of heterocycle W to form a strap represented by the formula:
   —(CH 2 ) I -Q-(CH 2 ) J —R—(CH 2 ) K —S—(CH 2 ) L —
 
 
       wherein I, J, K and L independently are integers from 0 to 10 and Q, R and S are independently selected from the group consisting of alkenyl, alkenylcycloalkenyl, alkenylcycloalkyl, alkyl, alkylcycloalkenyl, alkylcycloalkyl, alkynyl, aralkyl, aryl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylcycloalkyl, cycloalkenylalkyl, and heterocyclyl, aza, amide, ammonium, oxa, thia, sulfonyl, sulfinyl, sulfonamide, phosphoryl, phosphinyl, phosphino, phosphonium, keto, ester, alcohol, carbamate, urea, thiocarbonyl, borates, boranes, boraza, silyl, siloxy, silaza, and combinations thereof; and combinations of any of the above;
 wherein M is a cation of a transition metal; 
 and wherein X, Y and Z are independently selected from the group consisting of halide, oxo, aquo, hydroxo, alcohol, phenol, dioxygen, peroxo, hydroperoxo, alkylperoxo, arylperoxo, ammonia, alkylamino, arylamino, heterocycloalkyl amino, heterocycloaryl amino, amine oxides, hydrazine, alkyl hydrazine, aryl hydrazine, nitric oxide, cyanide, cyanate, thiocyanate, isocyanate, isothiocyanate, alkyl nitrile, aryl nitrile, alkyl isonitrile, aryl isonitrile, nitrate, nitrite, azido, alkyl sulfonic acid, aryl sulfonic acid, alkyl sulfoxide, aryl sulfoxide, alkyl aryl sulfoxide, alkyl sulfenic acid, aryl sulfenic acid, alkyl sulfinic acid, aryl sulfinic acid, alkyl thiol carboxylic acid, aryl thiol carboxylic acid, alkyl thiol thiocarboxylic acid, aryl thiol thiocarboxylic acid, alkyl carboxylic acid, aryl carboxylic acid, urea, alkyl urea, aryl urea, alkyl aryl urea, thiourea, alkyl thiourea, aryl thiourea, alkyl aryl thiourea, sulfate, sulfite, bisulfate, bisulfite, thiosulfate, thiosulfite, hydrosulfite, alkyl phosphine, aryl phosphine, alkyl phosphine oxide, aryl phosphine oxide, alkyl aryl phosphine oxide, alkyl phosphine sulfide, aryl phosphine sulfide, alkyl aryl phosphine sulfide, alkyl phosphonic acid, aryl phosphonic acid, alkyl phosphinic acid, aryl phosphinic acid, alkyl phosphinous acid, aryl phosphinous acid, phosphate, thiophosphate, phosphite, pyrophosphite, triphosphate, hydrogen phosphate, dihydrogen phosphate, alkyl guanidino, aryl guanidino, alkyl aryl guanidino, alkyl carbamate, aryl carbamate, alkyl aryl carbamate, alkyl thiocarbamate, aryl thiocarbamate, alkylaryl thiocarbamate, alkyl dithiocarbamate, aryl dithiocarbamate, alkylaryl dithiocarbamate, bicarbonate, carbonate, perchlorate, chlorate, chlorite, hypochlorite, perbromate, bromate, bromite, hypobromite, tetrahalomanganate, tetrafluoroborate, hexafluoroantimonate, hypophosphite, iodate, periodate, metaborate, tetraaryl borate, tetra alkyl borate, tartrate, salicylate, succinate, citrate, ascorbate, saccharinate, amino acid, hydroxamic acid, thiotosylate, and anions of ion exchange resins, or the corresponding anions thereof; 
 or X, Y and Z are independently selected from the group consisting of charge-neutralizing anions which are derived from any monodentate or polydentate coordinating ligand and a ligand system and the corresponding anion thereof; 
 or X, Y and Z are independently attached to one or more of R 1 , R′ 1 , R 2 , R′ 2 , R 3 , R′ 3 , R 4 , R′ 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R′ 7 , R 8 , R′ 8 , R 9 , R′ 9 , and R 10 ; 
 and n is an integer from 0 to 3. 
 
     
     
         42 . A method of treating cancer in accordance with  claim 30 , wherein the superoxide dismutase mimetic is a compound represented by the formula: 
       
         
           
           
               
               
           
         
       
       wherein a nitrogen of the macrocycle and two adjacent carbon atoms to which the nitrogen is attached independently form a substituted or unsubstituted, saturated, partially saturated or unsaturated nitrogen-containing heterocycle W having 2 to 20 carbon atoms, which may be an aromatic heterocycle in which case the hydrogen attached to the nitrogen which is both part of the heterocycle and the macrocycle and the R groups attached to the carbon atoms which are both part of the heterocycle and the macrocycle are absent;
 and two sets of two adjacent carbon atoms of the macrocycle independently form substituted or unsubstituted, saturated, partially saturated or unsaturated, cycles or heterocycles U and V having 3 to 20 carbon atoms; 
 and wherein R 1 , R′ 1 , R 2 , R′ 2 , R 3 , R′ 3 , R 4 , R′ 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R′ 7 , R 8 , R′ 8 , R 9 , R′ 9 , R 10 , and R′ 10  are each independently selected from the group consisting of hydrogen, alkenyl, alkenylcycloalkenyl, alkenylcycloalkyl, alkyl, alkylcycloalkenyl, alkylcycloalkyl, alkynyl, aralkyl, aryl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylcycloalkyl, cycloalkenylalkyl, and heterocyclyl, and aralkyl radicals and radicals attached to the α-carbon or α-amino acids, and —OR 11 , —NR 11 R 12 , —COR 11 , —CO 2 R 11 , —CONR 11 R 12 , —SR 11 , —SOR 11 , —SO 2 R 11 , —SO 2 NR 11 R 12 , —N(OR 11 )(R 12 ), —P(O)(OR 11 )(OR 12 ), —P(O)(OR 1 )(R 12 ), —OP(O)(OR 11 )(OR 12 ), and substituents attached to the α-carbon of α-amino acids, wherein R 11  and R 12  are independently hydrogen or alkyl; 
 and, optionally, one or more of R 1  and R 2  or R′ 2 , R 5  or R′ 5  and R 6  or R′ 6 , R 9  or R′ 9  and R 10  together with the carbon atoms to which they are attached independently form a substituted or unsubstituted and saturated, partially saturated, or unsaturated cycle or heterocycle having 3 to 20 carbon atoms; 
 and, optionally, one or more of R 2  and R′ 2 , R 5  and R′ 5 , R 6  and R′ 6 , and R 9  and R′ 9 , together with the carbon atom to which they are attached independently form a substituted or unsubstituted and saturated, partially saturated, or unsaturated cycle or heterocycle having 3 to 20 carbon atoms; 
 and, optionally, one or more of R 2  or R′ 2  and R 3 , R 4  and R 5  or R′ 5 , R 6  or R′ 6  and R 7 , or R 8  and R 9  or R′ 9  together with the carbon atoms to which they are attached independently form a substituted or unsubstituted nitrogen containing heterocycle having 3 to 20 carbon atoms, which may be an aromatic heterocycle in which case the hydrogen attached to the nitrogen which is both part of the heterocycle and the macrocycle and the R groups attached to the carbon atoms which are both part of the heterocycle and the macrocycle are absent; 
 and, optionally, one or more of R 1 , R 2 , R′ 2 , R 3 , R 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R 8 , R 9 , R′ 9 , and R 10 , together with a different one of R 1 , R 2 , R′ 2 , R 3 , R 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R 8 , R 9 , R′ 9 , and R 10 , which is attached to a different carbon atom in the macrocyclic ligand may be bound to form a strap represented by the formula:
   —(CH 2 ) I -Q-(CH 2 ) J —R—(CH 2 ) K —S—(CH 2 ) L —
 
 
 
       wherein
 I, J, K and L independently are integers from 0 to 10 and Q, R and S are independently selected from the group consisting of alkenyl, alkenylcycloalkenyl, alkenylcycloalkyl, alkyl, alkylcycloalkenyl, alkylcycloalkyl, alkynyl, aralkyl, aryl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylcycloalkyl, cycloalkenylalkyl, and heterocyclyl, aza, amide, ammonium, oxa, thia, sulfonyl, sulfinyl, sulfonamide, phosphoryl, phosphinyl, phosphino, phosphonium, keto, ester, alcohol, carbamate, urea, thiocarbonyl, borates, boranes, boraza, silyl, siloxy, silaza, and combinations thereof; and, optionally, one or more of R 1 , R 2 , R′ 2 ; R 3 , R 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R 8 , R 9 , R′ 9 , and R 10 , may be individually bound to an atom of heterocycles U, V and W to form a strap represented by the formula:
   —(CH 2 ) I -Q-(CH 2 ) J —R—(CH 2 ) K —S—(CH 2 ) L —
 
 
 
       wherein
 I, J, K and L independently are integers from 0 to 10 and Q, R and S are independently selected from the group consisting of alkenyl, alkenylcycloalkenyl, alkenylcycloalkyl, alkyl, alkylcycloalkenyl, alkylcycloalkyl, alkynyl, aralkyl, aryl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylcycloalkyl, cycloalkenylalkyl, and heterocyclyl, aza, amide, ammonium, oxa, thia, sulfonyl, sulfinyl, sulfonamide, phosphoryl, phosphinyl, phosphino, phosphonium, keto, ester, alcohol, carbamate, urea, thiocarbonyl, borates, boranes, boraza, silyl, siloxy, silaza, and combinations thereof; and combinations of any of the above; 
 wherein M is a cation of a transition metal; 
 and wherein X, Y and Z are independently selected from the group consisting of halide, oxo, aquo, hydroxo, alcohol, phenol, dioxygen, peroxo, hydroperoxo, alkylperoxo, arylperoxo, ammonia, alkylamino, arylamino, heterocycloalkyl amino, heterocycloaryl amino, amine oxides, hydrazine, alkyl hydrazine, aryl hydrazine, nitric oxide, cyanide, cyanate, thiocyanate, isocyanate, isothiocyanate, alkyl nitrile, aryl nitrile, alkyl isonitrile, aryl isonitrile, nitrate, nitrite, azido, alkyl sulfonic acid, aryl sulfonic acid, alkyl sulfoxide, aryl sulfoxide, alkyl aryl sulfoxide, alkyl sulfenic acid, aryl sulfenic acid, alkyl sulfinic acid, aryl sulfinic acid, alkyl thiol carboxylic acid, aryl thiol carboxylic acid, alkyl thiol thiocarboxylic acid, aryl thiol thiocarboxylic acid, alkyl carboxylic acid, aryl carboxylic acid, urea, alkyl urea, aryl urea, alkyl aryl urea, thiourea, alkyl thiourea, aryl thiourea, alkyl aryl thiourea, sulfate, sulfite, bisulfate, bisulfite, thiosulfate, thiosulfite, hydrosulfite, alkyl phosphine, aryl phosphine, alkyl phosphine oxide, aryl phosphine oxide, alkyl aryl phosphine oxide, alkyl phosphine sulfide, aryl phosphine sulfide, alkyl aryl phosphine sulfide, alkyl phosphonic acid, aryl phosphonic acid, alkyl phosphinic acid, aryl phosphinic acid, alkyl phosphinous acid, aryl phosphinous acid, phosphate, thiophosphate, phosphite, pyrophosphite, triphosphate, hydrogen phosphate, dihydrogen phosphate, alkyl guanidino, aryl guanidino, alkyl aryl guanidino, alkyl carbamate, aryl carbamate, alkyl aryl carbamate, alkyl thiocarbamate, aryl thiocarbamate, alkylaryl thiocarbamate, alkyl dithiocarbamate, aryl dithiocarbamate, alkylaryl dithiocarbamate, bicarbonate, carbonate, perchlorate, chlorate, chlorite, hypochlorite, perbromate, bromate, bromite, hypobromite, tetrahalomanganate, tetrafluoroborate, hexafluoroantimonate, hypophosphite, iodate, periodate, metaborate, tetraaryl borate, tetra alkyl borate, tartrate, salicylate, succinate, citrate, ascorbate, saccharinate, amino acid, hydroxamic acid, thiotosylate, and anions of ion exchange resins, or the corresponding anions thereof; 
 or X, Y and Z are independently selected from the group consisting of charge-neutralizing anions which are derived from any monodentate or polydentate coordinating ligand and a ligand system and the corresponding anion thereof; 
 or X, Y and Z are independently attached to one or more of R 1 , R 2 , R′ 2 , R 3 , R 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R 8 , R 9 , R′ 9 , and R 10 ; 
 and n is an integer from 0 to 3. 
 
     
     
         43 . A method of treating cancer in accordance with  claim 30 , wherein the superoxide dismutase mimetic is a compound represented by the formula: 
       
         
           
           
               
               
           
         
       
     
     
         44 . A kit comprising a superoxide dismutase mimetic and at least one additional pharmaceutical compound selected from the group consisting of a chemotherapeutic agent and a non-superoxide dismustase mimetic radical scavenger. 
     
     
         45 . A kit in accordance with  claim 44 , further comprising instructions for administering the superoxide dismutase mimetic to a subject in need of amelioration of oral mucositis resulting from a cancer therapy. 
     
     
         44 . A kit comprising a superoxide dismutase mimetic and at least one additional pharmaceutical compound selected from the group consisting of a chemotherapeutic agent and a non-superoxide dismustase mimetic radical scavenger. 
     
     
         45 . A kit in accordance with  claim 44 , further comprising instructions for administering the superoxide dismutase mimetic to a subject in need of amelioration of oral mucositis resulting from a cancer therapy. 
     
     
         46 . A kit in accordance with  claim 44 , wherein the chemotherapeutic agent is selected from a group consisting of all-trans retinoic acid, azacitidine, azathioprine, bleomycin, carboplatin, capecitabine, cisplatin, chlorambucil, cyclophosphamide, cytarabine, daunorubicin, docetaxel, doxifluridine, doxorubicin, epirubicin, epothilone, etoposide, fluorouracil, gemcitabine, hydroxyurea, idarubicin, imatinib, mechlorethamine, mercaptopurine, methotrexate, mitoxantrone, oxaliplatin, paclitaxel, pemetrexed, teniposide, tiguanine, valrubicin, vinblastine, vincristine, vindesine, vinorelbine. 
     
     
         47 . A kit in accordance with  claim 44 , wherein the non-superoxide dismutase mimetic radical scavenger is selected from the group consisting of amifostine and N-acetylcysteine. 
     
     
         48 . A kit in accordance with  claim 44 , wherein the superoxide dismutase mimetic is a compound represented by the formula: 
       
         
           
           
               
               
           
         
       
       wherein R 1 , R′ 1 , R 2 , R′ 2 , R 3 , R′ 3 , R 4 , R′ 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R′ 7 , R 8 , R′ 8 , R 9 , R′ 9 , R 10 , and R′ 10  are each independently selected from the group consisting of hydrogen, alkenyl, or R′ 5  and R 6  or R′ 6 , R 7  or R′ 7  and R 8  or R′ 8 , R 9  or R′ 9  and R 10  or R′ 10  together with the carbon atoms to which they are attached independently form a substituted or unsubstituted and saturated, partially saturated, or unsaturated cycle or heterocycle having 3 to 20 carbon atoms;
 and optionally, one or more of R 1  and R′ 1 , R 2  and R′ 2 , R 3  and R′ 3 , R 4  and R′ 4 , R 5  and R′ 5 , R 6  and R′ 6 , R 7  and R′ 7 , R 8  and R′ 8 , R 9  and R′ 9 , and R 10  and R′ 10 , together with the carbon atom to which they are attached independently form a substituted or unsubstituted and saturated, partially saturated, or unsaturated cycle or heterocycle having 3 to 20 carbon atoms; 
 and optionally, one or more of R 10  or R′ 10  and R 1  or R′ 1 , R 2  or R′ 2  and R 3  or R′ 3 , R 4  or R′ 4  and R 5  or R′ 5 , R 6  or R′ 6  and R 7  or R′ 7 , or R 8  or R′ 8  and R 9  or R′ 9  together with the carbon atoms to which they are attached independently form a substituted or unsubstituted nitrogen containing heterocycle having 3 to 20 carbon atoms, which may be an aromatic heterocycle in which case the hydrogen attached to the nitrogen which is both part of the heterocycle and the macrocycle and the R groups attached to the carbon atoms which are both part of the heterocycle and the macrocycle are absent; 
 and optionally, one or more of R 1 , R′ 1 , R 2 , R′ 2 , R 3 , R′ 3 , R 4 , R′ 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R′ 7 , R 8 , R′ 8 , R 9 , R′ 9 , R 10 , and R′ 10 , together with a different one of R 1 , R′ 1 , R 2 , R′ 2 , R 3 , R′ 3 , R 4 , R′ 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R′ 7 , R 8 , R′ 8 , R 9 , R′ 9 , R 10 , and R′ 10 , which is attached to a different carbon atom in the macrocyclic ligand may be bound to form a strap represented by the formula:
   —(CH 2 ) I -Q-(CH 2 ) J —R—(CH 2 ) K —S—(CH 2 ) L —
 
 
 
       wherein I, J, K and L independently are integers from 0 to 10 and Q, R and S are independently selected from the group consisting of alkenyl, alkenylcycloalkenyl, alkenylcycloalkyl, alkyl, alkylcycloalkenyl, alkylcycloalkyl, alkynyl, aralkyl, aryl, cycloalkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylcycloalkyl, cycloalkenylalkyl, and heterocyclyl, aza, amide, ammonium, oxa, thia, sulfonyl, sulfinyl, sulfonamide, phosphoryl, phosphinyl, phosphino, phosphonium, keto, ester, alcohol, carbamate, urea, thiocarbonyl, borates, boranes, boraza, silyl, siloxy, silaza, and combinations thereof; and combinations of any of the above;
 wherein M is a cation of a transition metal; 
 and wherein X, Y and Z are independently selected from the group consisting of halide, oxo, aquo, hydroxo, alcohol, phenol, dioxygen, peroxo, hydroperoxo, alkylperoxo, arylperoxo, ammonia, alkylamino, arylamino, heterocycloalkyl amino, heterocycloaryl amino, amine oxides, hydrazine, alkyl hydrazine, aryl hydrazine, nitric oxide, cyanide, cyanate, thiocyanate, isocyanate, isothiocyanate, alkyl nitrile, aryl nitrile, alkyl isonitrile, aryl isonitrile, nitrate, nitrite, azido, alkyl sulfonic acid, aryl sulfonic acid, alkyl sulfoxide, aryl sulfoxide, alkyl aryl sulfoxide, alkyl sulfenic acid, aryl sulfenic acid, alkyl sulfinic acid, aryl sulfinic acid, alkyl thiol carboxylic acid, aryl thiol carboxylic acid, alkyl thiol thiocarboxylic acid, aryl thiol thiocarboxylic acid, alkyl carboxylic acid, aryl carboxylic acid, urea, alkyl urea, aryl urea, alkyl aryl urea, thiourea, alkyl thiourea, aryl thiourea, alkyl aryl thiourea, sulfate, sulfite, bisulfate, bisulfite, thiosulfate, thiosulfite, hydrosulfite, alkyl phosphine, aryl phosphine, alkyl phosphine oxide, aryl phosphine oxide, alkyl aryl phosphine oxide, alkyl phosphine sulfide, aryl phosphine sulfide, alkyl aryl phosphine sulfide, alkyl phosphonic acid, aryl phosphonic acid, alkyl phosphinic acid, aryl phosphinic acid, alkyl phosphinous acid, aryl phosphinous acid, phosphate, thiophosphate, phosphite, pyrophosphite, triphosphate, hydrogen phosphate, dihydrogen phosphate, alkyl guanidino, aryl guanidino, alkyl aryl guanidino, alkyl carbamate, aryl carbamate, alkyl aryl carbamate, alkyl thiocarbamate, aryl thiocarbamate, alkylaryl thiocarbamate, alkyl dithiocarbamate, aryl dithiocarbamate, alkylaryl dithiocarbamate, bicarbonate, carbonate, perchlorate, chlorate, chlorite, hypochlorite, perbromate, bromate, bromite, hypobromite, tetrahalomanganate, tetrafluoroborate, hexafluoroantimonate, hypophosphite, iodate, periodate, metaborate, tetraaryl borate, tetra alkyl borate, tartrate, salicylate, succinate, citrate, ascorbate, saccharinate, amino acid, hydroxamic acid, thiotosylate, and anions of ion exchange resins, or the corresponding anions thereof; 
 or X, Y and Z are independently selected from the group consisting of charge-neutralizing anions which are derived from any monodentate or polydentate coordinating ligand and a ligand system and the corresponding anion thereof; 
 or X, Y and Z are independently attached to one or more of R 1 , R′ 1 , R 2 , R′ 2 , R 3 , R′ 3 , R 4 , R′ 4 , R 5 , R′ 5 , R 6 , R′ 6 , R 7 , R′ 7 , R 8 , R′ 8 , R 9 , R′ 9 , R 10 , and R′ 10 ; 
 and n is an integer from 0 to 3. 
 
     
     
         49 . A kit in accordance with  claim 44 , wherein the superoxide dismutase mimetic is a compound represented by the formula: