Copper-Catalyzed Synthesis of Xanthine–Chalcogenide Hybrids: Structural Diversity, DNA-Interaction Studies, and Docking Simulation

Abstract

Copper-catalyzed C(sp²)-H chalcogenylation was employed for the efficient synthesis of a series of xanthine-chalcogenide hybrids using diaryl dichalcogenides as chalcogen sources. The reactions proceeded under mild conditions, providing the desired selenium-and sulfur-containing xanthine derivatives in moderate to good yields. The structures of the synthesized compounds were unambiguously confirmed by spectroscopic techniques, including 1H- and 13-CNMR spectroscopy. The DNA-binding behavior of the obtained hybrids was investigated by UV-visible absorption titration with calf thymus DNA, revealing spectral features consistent with noncovalent DNA interaction. To further elucidate the binding mode at the molecular level, docking simulations were performed using a DNA macromolecular target, providing atomistic insight into the stabilizing interactions involved. Overall, this study demonstrates that the combination of xanthine scaffolds with chalcogenide moieties via a sustainable synthetic approach affords structurally diverse hybrids with relevant DNA interaction properties, highlighting their potential interest for further biological investigation.