Room-Temperature, Copper-Free, and Amine-Free Sonogashira Reaction in a Green Solvent: Synthesis of Tetraalkynylated Anthracenes and In Vitro Assessment of Their Cytotoxic Potentials.

The multifold Sonogashira coupling of a class of aryl halides with arylacetylene in the presence of an equivalent of Cs2CO3 has been accomplished using a combination of Pd(CH3CN)2Cl2 (0.5 mol %) and cataCXium A (1 mol %) under copper-free and amine-free conditions in a readily available green solvent at room temperature. The protocol was used to transform several aryl halides and alkynes to the corresponding coupled products in good to excellent yields. The rate-determining step is likely to involve the oxidative addition of Ar-X. The green protocol provides access to various valuable polycyclic aromatic hydrocarbons (PAHs) with exciting photophysical properties. Among them, six tetraalkynylated anthracenes have been tested for their anticancer properties on the human triple-negative breast cancer (TNBC) cell line MDA-MB-231 and human dermal fibroblasts (HDFs). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to find out the IC50 concentration and lethal dose. The compounds being intrinsically fluorescent, their cellular localization was checked by live cell fluorescence imaging. 4',6-Diamidino-2-phenylindole (DAPI) and propidium iodide (PI) staining was performed to check apoptosis and necrosis, respectively. All of these studies have shown that anthracene and its derivatives can induce cell death via DNA damage and apoptosis.

Multi-fold Sonogashira coupling: a new and convenient approach to obtain tetraalkynyl anthracenes with tunable photophysical properties.

For the first time, a direct single-step one-pot route to access nine new symmetric tetraalkynylated anthracenes via Pd(CH3CN)2Cl2/cataCXium®A catalyzed tetra-fold Sonogashira coupling is reported. Five of these tetraalkynylated anthracenes have been crystallographically characterized, with two of them exhibiting multiple interactions that significantly shorten the inter-planar distances in the solid-state structure. The rich photophysical properties exhibited by these molecules hold immense promise for future applications in sensors and optoelectronic devices. Two of the considered tetraalkynylated anthracenes comprising a D-π-A-π-D motif demonstrate solvatochromism and halochromism, with one of them showing a low bandgap of 1.79 eV. The remaining compounds demonstrate bandgaps in the range of 1.79-2.04 eV.