Anionic hexadeca-carboxylate tetrapyrazinoporphyrazine: synthesis and photodynamic studies of a water-soluble, non-aggregating photosensitizer

• Published in: RSC advances 2016-01, Vol.6 (12), p.164-177
• Main Authors: Machacek, Miloslav, Kollár, Jan, Miletin, Miroslav, Ku era, Radim, Kubát, Pavel, Simunek, Tomas, Novakova, Veronika, Zimcik, Petr
• Format: Article
• ISSN: 2046-2069
• DOI: 10.1039/c5ra25881b

A sodium salt of zinc tetrapyrazinoporphyrazine bearing eight 3,5-dicarboxylatophenyl substituents ( 1 ) was synthesized. The presence of sixteen negative charges in a rigid arrangement on the periphery of the macrocycle inhibited its aggregation in water or buffers at pH > 5.8. Strong aggregation was, however, observed in buffers at pH < 4.8 due to the protonation of carboxylate functions. Fluorescence microscopy revealed that the compound localized to lysosomes and endosomes in cells. The compound's photodynamic activity on HeLa cancer cells (IC 50 = 5.7 ± 1.1 μM) was found to be influenced by both pH and interactions with serum proteins. This was demonstrated with a detailed in vitro study based on the inhibition of vacuolar H + -ATPase using bafilomycin A 1 , which increased the intracellular fluorescence of 1 . Compound 1 also formed interactions with serum proteins that partially quenched its excited states; however, they also protected the compound from self-aggregation at low pH. Photodynamic activity of hexadeca-carboxylate tetrapyrazinoporphyrazine is largely influenced by intracellular pH and its interaction with serum proteins.