Design, synthesis, spectral investigations and biological activity of fluorinated phthalocyanine conjugated with galactose and comparison to its non-fluorinated counterpart

• A novel perfluorinated phthalocyanine/galactose conjugate was synthesized.
• Phthalocyanine/galactose conjugates were active as a PDT agent in vitro.
• A fluorinated conjugate showed an efficient photo-dynamic effect in vitro.
• A non-fluorinated conjugate is less active in vitro than the fluorinated counterpart.

Photofrin® is a clinically useful photosensitizer of photodynamic therapy (PDT) used for cancer treatment, but has some disadvantages, including its weak absorbance when excited at 630 nm. Hence, the development of novel photosensitizers with greater than 630 nm absorbance is required. In addition, photosensitizers must have suitable balance between lipophilicity and hydrophilicity to allow for selective accumulation in tumor cells. Herein, we describe the design and synthesis of a novel perfluorinated phthalocyanine/galactose conjugate 1a suitable for use as a PDT agent. Our novel phthalocyanine/galactose conjugate 1a displays absorption at 600–750 nm. Four of its peripheral galactopyranosyl moieties resulted in improved water solubility confirmed by a 1-octanol/water partition coefficient log P value. Moreover, 12 fluorine atoms at the peripheral position of 1a simultaneously endowed the macrocycle with suitable hydrophobicity. In vitro biological activity of our perfluorinated phthalocyanine/galactose conjugate 1a showed a much more efficient photo-dynamic effect than the non-fluorinated phthalocyanine/galactose counterpart 1b. This is one of the clear examples of fluorine effect on biological activity.

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