A reinvestigation of the reaction of coumarins with superoxide in the liposomal bilayer: correlation between depth and reactivity.
Afri et al. reported in this journal (Free Radic. Biol. Med.32:605-618; 2002) that a direct relationship exists between the depth of alkanoylcoumarins 1 within the liposomal lipid bilayer and the rate at which they undergo superoxide-mediated saponification. These results were based on a correlation between the (13)C NMR chemical shift of polarizable carbonyl carbons and the E(T)(30) polarity they sense. Subsequent studies challenged these results, however, demonstrating that, in conjugated ketones and aldehydes, charge separation influences the E(T)(30) polarity measured. To elucidate whether this is true for conjugated esters such as coumarins as well, the nonconjugated analogs 3,4-dihydrocoumarins 11 and 15 were intercalated within DMPC liposomal bilayers and their relative locations within the liposomal bilayer were determined. The length of the alkyl chain substituted at C-4 and C-10 influences the depth of the substrates within the liposome. The location of these 3,4-dihydrocoumarins corresponds well with the conjugated analog coumarin 1-confirming the validity of the abovementioned results of Afri et al. The lack of substantial charge separation in the coumarin 1 system presumably results from the "swamping-out" effect of the ester oxygen. Instead of 1,3-delocalization of charge, typical of conjugated systems, delocalization of the nonbonding pair on the ester oxygen predominates.
Shachan-Tov
Sharona
S
The Ethel and David Resnick Chair in Active Oxygen Chemistry, Department of Chemistry, Ramat Gan 52900, Israel.
Afri
Michal
M
Frimer
Aryeh A
AA
D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry*; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D004952:Esters / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000737:chemistry
D003374:Coumarins; D004952:Esters; D008051:Lipid Bilayers; D008081:Liposomes; D013481:Superoxides; C026308:3,4-dihydrocoumarin; D004134:Dimyristoylphosphatidylcholine