Mild Synthesis of a Family of Planar Triazinium Cations via Proton-Assisted Cyclization of Pyridyl Containing Azo Compounds and Studies on DNA Intercalation

An efficient synthesis of a family of heteroaromatic triazinium compounds, [2a]X−[2g]X (X= Cl, ClO4, NO3, and HSO4), from 2-(arylazo)pyridines via proton-catalyzed heterocyclization is described. Characterization of the compounds is made by different spectroscopic, electrochemical techniques, as well as single-crystal structure determination of the triflate salt of a representative compound, [2a]CF3SO3. The bond parameters indicate that the tricyclo compound, 2a+, is planar and aromatic with a N−N bond length of 1.275(6) Å. These exhibited fluorescence with an emission maximum in the range of 540–535 nm with moderate quantum yields. The triazinium salts can be reduced in two successive one-electron steps as probed by cyclic voltammetry and coulometry. The paramagnetic radical intermediate 2a• is distinguished by a sharp and intense EPR spectrum. Fluorescence spectroscopy, circular dichroism, cyclic voltammetry, viscosity measurements, together with DNA melting studies have been used to characterize the binding of 2a+ with calf thymus DNA. The emission quenching of the compound by [Fe(CN)6]4− decreased when bound to DNA. As determined by a MTT assay, 2a+ exhibited significant cytotoxicity at a higher concentration range of 1 mg/mL to 1 µg/mL; however, the % survival ratio increased with dilution. Cellular uptake studies of the referenced compound were followed by FACS analysis.