Physical and chemical modifications of adriamycin:iron complex by phospholipid bilayers

Adriamycin (ADM) and the ADM:Fe(III) complex both interact with phosphatidylcholine bilayers in aqueous vesicle dispersions. The immediate interaction of either ADM or ADM:Fe(III) with phospholipid causes little change in their absorption or emission spectra, but considerably increases the steady-state fluorescence anisotropy of both species. This is followed by a conversion of the ADM:Fe(III) complex (but not of metal-free ADM) into a new compound in periods ranging from minutes to hours depending upon the Fe(III) concentration. This reaction does not require the presence of unsaturated acyl chains, net negatively charged phospholipid head groups, or the participation of molecular oxygen. This new compound has a characteristic absorption and fluorescence emission spectra which differ from those of the ADM:Fe(III) or of metal-free ADM. It can be isolated from the aqueous lipid dispersion by Folch extraction under acidic conditions. It is very lipophilic in comparison to ADM or the ADM:Fe(III) complex. It may be similar to the compound reported to form between cardiolipin and Adriamycin. Preliminary results indicate that it also forms spontaneously in intact biological membranes. Its highly lipophilic character may confine it to bilayers and membranes.