Substituted Porphyrins

Abstract

A series of ortho isomers of meso tetrakis N-alkylpyridylporphyrins (alkyl being methyl, ethyl, n-propyl, n-butyl, n-hexyl, and n-octyl) and their Mn(III) complexes were synthesized and characterized by elemental analysis, uv/vis spectroscopy, electrospray ionization mass spectrometry and electrochemistry. An increase in the number of carbon atoms in the alkyl chains from 1 to 8 is accompanied by an increase in: (a) lipophilicity measured by the chromatographic retention factor, R f ; (b) metal-centered redox potential, E 1/2 from +220 to +367 mV vs NHE, and (c) proton dissociation constant, pK a2 from 10.9 to 13.2. A linear correlation was found between E 1/2 and R f of the Mn(III) porphyrins and between the pK a2 and R f of the metal-free compounds. As the porphyrins become increasingly more lipophilic, the decrease in hydration disfavors the separation of charges, while enhancing the electron-withdrawing effect of the positively charged pyridyl nitrogen atoms. Consequently, the E 1/2 increases linearly with the increase in pK a2 , a trend in porphyrin basicity opposite from the one we previously reported for other water-soluble Mn(III) porphyrins. All of these Mn(III) porphyrins are potent catalysts for superoxide dismutation (disproportionation). Despite the favorable increase of E 1/2 with the increase in chain length, the catalytic rate constant decreases from methyl (log k cat =7.79) to n-butyl, and then increases such that the n-octyl is as potent an SOD mimic as are the methyl and ethyl compounds. The observed behavior originates from an interplay of hydration and steric effects that modulate electronic effects.

1 .- 5 . (canceled) 
     
     
         6 . A method of protecting cells from oxidant-induced toxicity comprising contacting said cells with a protective amount of a compound under conditions such that the protection is effected, said compound having the formula 
       
         
           
           
               
               
           
         
       
       wherein
 each R is, independently, an alkyl group of greater than 8 carbons, 
 each A is, independently, hydrogen or a halogen, 
 M is a metal selected from the group consisting of manganese, iron, copper, cobalt, nickel and zinc, and 
 Z −  is a counterion. 
 
     
     
         7 . The method according to  claim 6  wherein said cells are mammalian cells. 
     
     
         8 . A method of treating a pathological condition of a patient resulting from oxidant-induced toxicity comprising administering to said patient an effective amount of a compound under conditions such that the treatment is effected, said compound having the formula 
       
         
           
           
               
               
           
         
       
       wherein
 each R is, independently, an alkyl group of greater than 8 carbons, 
 each A is, independently, hydrogen or a halogen, 
 M is a metal selected from the group consisting of manganese, iron, copper, cobalt, nickel and zinc, and 
 Z −  is a counterion. 
 
     
     
         9 . A method of treating a pathological condition of a patient resulting from degradation of NO • , comprising administering to said patient an effective amount of a compound under conditions such that the treatment is effected, said compound having the formula 
       
         
           
           
               
               
           
         
       
       wherein
 each R is, independently, an alkyl group of greater than 8 carbons, 
 each A is, independently, hydrogen or a halogen, 
 M is a metal selected from the group consisting of manganese, iron, copper, cobalt, nickel and zinc, and 
 Z −  is a counterion. 
 
     
     
         10 . A method of treating a patient for inflammatory lung disease comprising administering to said patient an effective amount of a compound under conditions such that the treatment is effected, said compound having the formula 
       
         
           
           
               
               
           
         
       
       wherein
 each R is, independently, an alkyl group of greater than 8 carbons, 
 each A is, independently, hydrogen or a halogen, 
 M is a metal selected from the group consisting of manganese, iron, copper, cobalt, nickel and zinc, and 
 Z −  is a counterion.