Fluorinated photosensitizers: Synthesis, photophysical, electrochemical, intracellular localization, in vitro photosensitizing efficacy and determination of tumor-uptake by ¹⁹F in vivo NMR spectroscopy

For in vivo NMR studies, starting from pyrroles, a series of fluorinated porphyrins were synthesized by following the MacDonald reaction conditions. Upon reaction with osmium tetroxide, a fluorinated porphyrin containing four trifluoromethyl groups (12 fluorine units) was converted into the related chlorin and bacteriochlorin which exhibited long-wavelength absorptions at 652 and 720 nm, respectively. All compounds produced good singlet oxygen production efficiency. A comparative study of nine porphyrins with and without fluorine substituents indicated no adverse effects of the presence of fluorinated groups in the photophysical properties of the porphyrins, chlorins or bacteriochlorins. The first and second one-electron reduction potentials (vs SCE) of the investigated compounds range between -1.29 and -1.49 V and between -1.66 and -1.84 V in PhCN containing 0.1 M TBAP. UV-visible spectroelectrochemical data suggested the formation of π-anion and π-cation radicals upon the first reduction and first oxidation. The in vivo ¹⁹F MR study of a representative fluorine labeled compound with twelve equivalent fluorines confirmed the presence of the fluorine labeled sensitizer in mouse (C3H/HeJ) implanted with RIF tumors on mouse foot dorsum by inoculating 2×10 ⁵ cells (the studies were repeated on four tumored mice to confirm the feasibility and reproducibility). All fluorinated compounds were found to be quite effective in vitro. In a comparative intracellular localization study with Rhodamine-123 in RIF tumor cells, the most soluble porphyrin containing two propionic ester side chains was found to localize in mitochondria as well as the related chlorin and bacteriochlorin.