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Chiral recognition of DNA molecules is important because much evidence has indicated that transformations of chirality and diverse conformations of DNA are involved in a series of key biological events. Among these, enrichment of G-quadruplexes (GQs) in the genome, and the exploration of their multiple structures, has aroused great interest. Herein, we compared nearly 100 different sequences with 3′-tail sequences of variable length or different linkers or diverse loops and mutative ionic concentrations. All sequences were capable of forming stable GQs, with fluorescence signal enhancement upon binding with Δ- and Λ- [Ru(bpy)2(dppz-idzo)]2+ (Δ/Λ-1). Our results show that multiple factors, including the 3′-tail length, linkers, loop length and ionic concentration, regulate the enantioselectivity of GQs. Furthermore, molecular docking simulations revealed that chiral recognition of GQs depends on the binding site. To the best of our knowledge, this is the first systematic study regarding the regulation of multi-factors for GQ selectivity of chiral Ru-complexes. These results will serve as a useful reference for enantioselective recognition of genomic GQs and may facilitate the development of chiral anticancer agents for targeting GQs. [ABSTRACT FROM AUTHOR]

To overcome the acquired resistance and the significant side-effects of the reported drugs, four new ruthenium(II) complexes with alkynyl (Ru1, Ru2, Ru3, Ru4) were designed and synthesized. Ru1, Ru2, Ru3 and Ru4 were characterized by ESI-MS, 1H NMR, 1H–1H COSY NMR and elemental analysis. Compared with Ru2, Ru3, Ru4 and cisplatin, the anti-tumor experiments in vitro and vivo confirmed that Ru1 could most effectively inhibit tumor growth. In the experiments of safety evaluation in vivo, Ru1 could avoid any detectable side-effects compared with cisplatin. DNA binding experiments and cell cycle experiments showed that Ru1 exhibited the strongest DNA binding ability and interfered with the cell cycle by inserting DNA to inhibit tumor growth. The study demonstrated that Ru1 had the potential to be an exciting new drug candidate for glioblastoma treatment. [ABSTRACT FROM AUTHOR]