Stronger Affinity of Water-Soluble Cationic Porphyrins to Cancer DNA under Acidic Conditions as a Basis for Selectivity

High Resolution Image Download MS PowerPoint Slide The affinities of porphyrins to healthy and cancer DNA under physiological and acidic conditions were studied. Titration of meso -tetra(4- N -hydroxyethylpyridyl)porphyrin and its Ag-substituted derivative solutions with DNAs, isolated from healthy and tumor tissues, has been performed. Using the simple neighbor-exclusion model of McGhee and von Hippel with the binding isotherm formula optimized for fitting errors, we found the binding constant K b and exclusion parameter n from the titration absorption spectra. It was shown that the binding parameters of porphyrins to DNA under acidic conditions are higher than those under physiological conditions. The K b of porphyrins with cancer DNA at pH 6.4 is an order of magnitude higher, and n is lower than that of healthy DNA at pH 7.4. The enhanced affinity of porphyrins for cancer DNA indicates that conformational alterations in the DNA structure create more-accessible binding sites. This selective interaction underscores the potential of porphyrins as effective agents for a targeted anticancer therapy.