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Cytotoxic bifunctional DNA binders of the general formula (η 6 -cym) Ru (phe) 2 (μ -BL) Cl 4, where cym = p-cymene, phe = 1, 10-phenanthroline, BL = 4, 4′-bipyridine (BL-1), (1), 1, 2-bis (4-pyridyl) ethane (BL-2), (2) and 1, 3-bis (4-pyridyl) propane (BL-3), (3), were investigated for their binding properties with B-type DNA sequences d (5′-CGCGCG-3′), d (5′-CTTTTGCAAAAG-3′) and CT-DNA using NMR spectroscopy and fluorescence titrations. The results revealed distinct binding modes and affinities, significantly influenced by both the DNA sequence and the length of the BL. The interactions were non-selective and occurred through multiple binding modes. Complex (1) was found to disrupt the W. -C. imino hydrogen bonds at both C·G and A·T base pairs, effectively mimicking the DNA strand separation mechanism by helicase enzymes. In contrast, the binding of (2) does not disrupt the C. -W. GN1-H imino hydrogen bonds in the G·C-only sequence d (5′-CGCGCG-3′) 2 but it selectively disrupts the T2N3H imino hydrogen bond of the T2·A11 base pair in the AT-rich sequence d (5′-CTTTTGCAAAAG-3′). Complex (3) induced localized unwinding of the helix near the center of the d (5′-CGCGCG-3′) 2. The DNA binding affinities of complexes (1) – (3) exhibit strong sequence dependence, with binding constants (K b) ranging from 1. 23 × 10 3 M −1 to 6. 34 × 10 5 M −1. Binuclear Ru (II) -arene complexes cause DNA unwinding. • Explores the binding affinity for binuclear ruthenium – arene complexes with various DNA models. • Discusses how the difference in length of the bridging ligand for each binuclear complex affects its binding to DNA. • Examines any possible sequences specificity for the binding of the binuclear ruthenium – arene complexes.
Thomos et al. (Mon,) studied this question.