Photophysical, DFT Calculations, Electrochemical, and DNA-Binding Properties of 7-Chloroquinoline-Organochalcogen Hybrids

Abstract

Quinoline-based chromophores are of great interest in medicinal chemistry due to their ability to bind DNA, modulate key biochemical pathways, and serve as fluorescent probes for molecular recognition and therapeutic applications. The incorporation of chalcogen atoms further broadens the functional scope of these systems; S and Se can modulate electronic distribution, polarizability, and photophysical behavior through chalcogen bonding and heavy-atom effects. Building on these properties, we rationally designed and synthesized 11 quinoline- and organochalcogen-based derivatives, achieving yields of 10–75% through a simple and efficient method involving the introduction of various electron-donating and electron-withdrawing substituents, as well as different chalcogen atoms (Se and S), including one Se derivative in a higher oxidation state. These compounds were subjected to systematic photophysical, electrochemical, reactive oxygen species generation, and DNA-binding studies. The fluorescence analyses revealed intense UV absorption and low to moderate fluorescence quantum yields, both of which were by the nature of the chalcogen atom. Selenium derivatives displayed reduced emission and were more susceptible to oxidation, whereas selenoxide exhibited a larger electrochemical band gap. The data indicated a preference for minor groove DNA binding, with the π-extended derivative showing the highest affinity. This integrated approach highlights the potential of quinoline-organochalcogen hybrids as multifunctional platforms for advanced applications in photophysics, electrochemistry, and DNA-targeted therapeutics.