Boron subphthalocyanines (SPcs) are aromatic macrocycles that possess a combination of physical and optical properties that make them excellent candidates for application as fluorescent imaging probes. These molecules have intense electronic absorption and emission, and structural versatility that allows for specific tuning of physical properties. Herein, we report the synthesis of a series of low-symmetry fluorinated SPcs and compare them to analogous compounds with varying numbers of peripheral fluorine atoms and varied aromaticity. Across the series, with increasing addition of fluorine atoms to the periphery of the ring, a downfield chemical shift in 19F NMR and a bathochromic shift of electronic absorption were observed. Expanding the size of the aromatic ring by replacing peripheral benzo- groups with naphtho- groups prompted a far more drastic bathochromic shift to absorption and emission. Fluorescence quantum yields (Φf) proved to be sufficiently high to observe intracellular fluorescence from MDA-MB-231 breast tumor cells in vitro by epifluorescence microscopy; fluorination proved vital for this purpose to improve solubility. This report lays the groundwork for the future development of these promising SPcs for their ultimate application as near-infrared (NIR) fluorescent imaging probes in biological systems.
Subphthalocyanines (SPcs), a platform of tripyrrolic macrocycles, offer a combination of optical and physical properties that make them highly applicable in a variety of fields. Incorporation of low‐symmetry elements allows for fine tuning of these properties by synthetic design. Herein, we report the synthesis of mixed fluorinated phenylthio‐ SPcs of the forms SPc(AnB3‐n) and SPc(AnC3‐n) where ‘A’ is tetrafluorobenzo‐, ‘B’ is 1,4‐bis(phenylthio)benzo‐, and ‘C’ is 1,4‐bis(phenylthio)naphtho‐, and n is an integer 1–2. Appended thioethers have a deshielding effect on 19F NMR spectra and prompt a bathochromic shift of electronic absorption and emission. Combined with increased aromaticity in the ‘AC’ series, phenylthio‐ groups shift SPc emission to the edge of the near infrared region (λf=680 nm), highlighting the potential of these molecules for optical imaging.
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 (F3SPc). The constitutional isomers F3SPc(C3) and F3SPc(C1) are readily separable by chromatography, and their identity and purity have been confirmed by 1H NMR, 19F NMR, HR APCI-MS, and HPLC. Unsurprisingly, these structurally similar F3SPcs have identical electronic absorption (λmax = 557 nm; tetrahydrofuran (THF)) and emission (λem = 574 nm; Φf = 0.27–0.28; THF). Strong fluorescence from MDA-MB-231 breast tumor cells was observed following treatment with F3SPc(C3) and F3SPc(C1) (50 µM F3SPc, 15 min), further highlighting the importance of even a limited number of peripheral fluorine atoms for this type of application.
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