The effect of tissue and cellular pH on the selective biodistribution of porphyrin-type photochemotherapeutic agents: A volumetric titration study

Volumetric titration of aqueous solutions of haematoporphyrin IX (HP) yields two inflexion points, whereas four p K values can be obtained via mathematical fitting of the experimental data. Assignment of all p K protonation sites is made. A zwitterion is proposed as the neutral species of HP. Evaluation of the p K values of HP in the presence of sodium dodecyl sulphate (SDS) leads to a drastically altered ionic species distribution. On the basis of the distribution diagrams obtained, a pH-sensitive twofold mechanism is proposed for the selective biodistribution of porphyrin-type photochemotherapeutic agents, one involving tissue distribution and the other involving cell membrane penetration by the neutral zwitterion.