Nickel‐Catalyzed Construction of Dibenzoxathiepine and Dibenzothiazepine Frameworks as H‐Telo G‐Quadruplex DNA Binders

A series of medium‐ring heterocycles, including dibenzoxathiepine and dibenzothiazepine derivatives bearing tetra‐substituted exocyclic olefins, were synthesized via a ligand‐free nickel‐catalyzed one‐pot cyclocarbonickelation‐arylation cascade of functionalized bromoalkyne substrates. In this study, these synthesized ligands were evaluated for their binding affinity toward various G‐quadruplex (GQ) and duplex DNA structures using biophysical such as UV–Vis absorption, fluorescence spectroscopy, fluorescence anisotropy, time‐resolved decay, circular dichroism, thermal melting, thermodynamic analysis, and in silico studies (molecular docking and simulation studies). Owing to their biological significance, GQ‐DNA motifs have emerged as attractive targets for anticancer drug development. Among the tested compounds, ligand 3i demonstrated high selectivity for the H‐Telo GQ‐DNA over other GQ forms and duplex DNA. The thermodynamic and spectroscopic data collectively reveal that hydrophobic and π–π stacking interactions drive the ligand‐GQ association. This recognition suggests that ligand 3i may serve as a promising ligand and also potential candidates for further investigation in cancer cells. Overall, the findings provide valuable insights into ligand‐GQ interactions and may support the development of GQ‐targeted agents, contributing to the broader understanding of GQ‐DNA recognition and therapeutic design. These findings also establish a structure‐function relationship linking the heterocyclic framework to GQ recognition.