Incorporation of metalloporphyrin inhibitors of heme oxygenase into micelles and liposomes.
Academic Article
Overview
abstract
Spectral and photodynamic properties of a porphyrin are sensitive to the environment in which it is localized. By comparison of absorption maxima of porphyrins bound to micelles, proteins or artificial membranes with peak wavelengths in homogeneous solutions of known dielectric constant, the relative polarity of the microenvironment surrounding a porphyrin can be estimated. We have focused our examination on the ability of two synthetic metalloporphyrin inhibitors of heme oxygenase, Sn(IV)-mesoporphyrin (SnMP) and Zn(II)-mesoporphyrin (ZnMP), to partition into charged and uncharged detergent micelles and liposomes. SnMP and ZnMP are intercalated into micelles with cationic surface charges but only ZnMP into nonionic micelles, suggesting that the ionic character of the two anionic axial ligands of SnMP, as well as that of the ionized carboxylic acids of both porphyrins, is a predominant force in the interactions of these compounds. Absorbance shifts of SnMP and ZnMP bound to serum albumin suggest that both porphyrins are localized within an environment with polarity similar to that of ethanol. Spectral changes upon incubation of ZnMP into liposomes (with or without surface charges) indicate that the porphyrin is incorporated into the polar region of the bilayer, i.e. at the border between hydrophilic headgroups and hydrophobic lipids. Illumination of ZnMP within the liposomal membrane resulted in a rapid rate of oxygen uptake, consistent with lipid peroxidation occurring within the bilayer.
