CAN SUPEROXIDE ORGANIC-CHEMISTRY BE OBSERVED WITHIN THE LIPOSOMAL BILAYER

2-(Dimethylamino)fluorene (1a) and -benzoyloxy-2,3,7,8,12,13,17,18-oct aethylporphyrin (4) react with superoxide anion radical (generated fro m KO2/18-crown-6 polyether) in aprotic media. Yet, when incorporated i nto the lipid bilayer of dimyristoyl phosphatidylcholine liposomes, th ese two substrates are inert to superoxide, generated enzymatically (x anthine oxidase/acetaldehyde) or radiolytically (Co-60 Or Cs-137 sourc e/formate solution). On the other hand, 7-acetoxy-4-methylcoumarin (6) , which reacts with superoxide in aprotic media yielding the correspon ding 4-methylumbelliferone (7), also gives the same product when incor porated within the liposomal bilayer and reacted with radiolytically o r enzymatically generated superoxide, In the latter case, the reaction is inhibited by SOD. NMR studies indicate that in contradistinction t o the highly lipophilic la and 4, which presumably lie well within the lipid bilayer, 7 lies in a highly polar region of the bilayer. These results suggest that superoxide anion does not penetrate deep into the liposomal bilayer; nevertheless, superoxide reactions can, indeed, be observed, provided the active site of the substrate lies at or near t he lipid-water interface.