Determination of n-octanol/water partition and membrane binding of cationic porphyrins

Porphyrin and their derivatives are being systematically studied as photosensitizers for photodynamic therapy. The ability to predict their membrane partition properties is of key importance to unveil their in vivo activity and applications. Several n-octanol/water partition coefficients (log POW) of porphyrin derivatives have been reported in the literature but large discrepancies have been observed. Reproducible and reliable log POW data for a series of 20 cationic meso-phenyl(pyridyl)porphyrin derivatives were determined by correlating log POW with the partition coefficients measured in a more adequate n-butanol/water system. Linear correlations as a function of the number of positively charged groups bound to the periphery of the porphyrin rings were found within each series. A significant effect of the stereochemistry and nature of the positively charged substituents was also observed, but diminished steadily converging to a similar value in the mono-substituted derivatives. Binding constants to liposomes were shown to be proportional to log POW, except for the cis-isomers of doubly charged porphyrins. The cis-isomer presented smaller log POW and higher membrane affinity. The effect was explained based on the amphiphilic nature of the cis-porphyrin.