Introducing the Tellurophene-Appended BODIPY: PDT Agent with Mass Cytometry Tracking Capabilities

Abstract

The synthesis and characterization of the first BODIPY appended to the five-membered heterocylic tellurophene [Te] moiety is reported. By incorporating tellurophene at the meso position, the tellurophene-appended boron-dipyrromethene dye (BODIPY) acts as a multimodal agent, becoming a potent photosensitizer with a mass cytometry tag. To synthesize the compound, we developed a method to enable late-stage Suzuki–Miyaura coupling by preparing and isolating tellurophene-2-BPin in a one-step procedure from the parent tellurophene. Coupling to a meso-substituted BODIPY functionalized with a pendant aryl bromide provides the desired tellurophene-appended BODIPY. This compound demonstrated a singlet oxygen quantum yield of 0.26 ± 0.01 and produced a light dose-dependent cytotoxicity with nanomolar IC50 values against 2D cultured HeLa cells and high efficacy against 3D cultured HeLa tumor spheroids, proving to be a strong photosensitizer. The presence of the tellurophene moiety could be detected using mass cytometry, thus showcasing the ability of a tellurophene-appended BODIPY as a novel photodynamic-therapy–mass-cytometry theranostic agent.

BODIPYs with Chalcogenophenes at Boron: Synthesis and Properties

“…All [ E ]-BODIPYs were fluorescent, although compound 2 displayed only very weak fluorescence above the background (Figure S7). Consequently, all the [ E ]-BODIPYs have potential as diagnostic agents, in addition to their use in photodynamic therapy, courtesy of their fluorescence ( 3 – 5 ) and their potential as multichannel probes of use in mass cytometry given the ability to incorporate single-isotope tellurium ( e.g ., 2 ) …”

“…2,6-Diethyl-1,3,5,7-tetramethyl-4,4-ditellurophenylBODIPY, 2. Following GP, a solution of tellurophene 12 (130 mg, 0.7 mmol) in tetrahydrofuran was lithiated using n-butyllithium (0.8 mmol) and then added to a solution of 1 (100 mg, 0.33 mmol) in tetrahydrofuran. After work-up and column chromatography (0 ⇒ 20% dichloromethane/hexanes), the desired product was afforded as a scarlet red solid (51 mg, 25% yield).…”

“…Boron-dipyrromethene dyes (BODIPYs, 4-disubstituted-4-bora-3 a ,4 a -diaza- s -indacenes) have garnered significant attention as photoactive species. This interest comes by virtue of the high structural tunability of BODIPYs (Figure ), enabling applications in the fields of labeling reagents, − switches, , chemosensors, − photodynamic therapy (PDT) agents, − solar capture, and laser dyes …”

Substitution at boron in BODIPYs

“…30% of cancer deaths are related to late diagnosis, accurate and early monitoring may be the most accessible route to increasing cancer survival rates thus lending urgency to the development of robust diagnostic probes. [32][33][34] Beyond their use as fluorescent bioprobes, the electronic tunability of BODIPYs has led to utility as photosensitizers for photodynamic therapy 35 and in dye-sensitized solar cells for photovoltaic technology. 36 The planar core, facile functionalization and tunable HOMO-LUMO gap of BODIPYs offer significant promise in this regard.…”

“…Beyond their use as fluorescent bioprobes, the electronic tunability of BODIPYs has led to utility as photosensitizers for photodynamic therapy 35 and in dye-sensitized solar cells for photovoltaic technology. 36 The planar core, facile functionalization and tunable HOMO–LUMO gap of BODIPYs offer significant promise in this regard.…”