Synthesis of the C(3) and C(1) Constitutional Isomers of Trifluorosubphthalocyanine and Their Fluorescence within MDA-MB-231 Breast Tumor Cells

Metal tetrapyrrole macrocycles such as porphyrins and chlorins are ubiquitous in nature. Synthetic analogs, including phthalocyanines, have found applications in medicine, particularly as photosensitizers for photodynamic therapy and as fluorescent imaging probes. Tripyrrolic macrocycles, called subphthalocyanines (SPcs) with a smaller boron atom at their core, have similar potential as optical agents. We have recently reported a series of mixed fluorinated SPcs with varying aromaticity, showing that electronic absorption and emission are synthetically tunable across the far visible region, and that the inclusion of 4–12 peripheral fluorine atoms results in strong fluorescence within MDA-MB-231 breast tumor cells. Further probing this system, we report herein the synthesis and characterization of boron trifluorosubphthalocyanine chloride (F(3)SPc). The constitutional isomers F(3)SPc(C(3)) and F(3)SPc(C(1)) are readily separable by chromatography, and their identity and purity have been confirmed by (1)H NMR, (19)F NMR, HR APCI-MS, and HPLC. Unsurprisingly, these structurally similar F(3)SPcs have identical electronic absorption (λ(max) = 557 nm; tetrahydrofuran (THF)) and emission (λ(em) = 574 nm; Φ(f) = 0.27–0.28; THF). Strong fluorescence from MDA-MB-231 breast tumor cells was observed following treatment with F(3)SPc(C(3)) and F(3)SPc(C(1)) (50 µM F(3)SPc, 15 min), further highlighting the importance of even a limited number of peripheral fluorine atoms for this type of application.