Copper-catalyzed xanthine-chalcogenide hybrids: synthesis, DNA binding and docking.

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 13C-NMR 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 as candidates for further biological investigation.