DNA binding studies and cytotoxicity of a dinuclear Pt^II diazapyrenium-based metallo-supramolecular rectangular box

The interaction with native DNA of a 2,7-diazapyrenium-based ligand 1 and its Pt^II rectangular metallacycle 2 is explored through circular and linear dichroism and fluorescence spectroscopies. The metal-free ligand 1 binds through intercalation, with a binding constant of approximately 5 × 10⁵a M^-1, whereas the metallacycle 2 binds and bends the DNA with a binding constant of 7 × 10⁶a M^-1. PCR assays show that metallo-supramolecular box 2 interferes with DNA transactions in vitro whereas the intercalator 1 does not. The metallacycle is active against four human cancer cell lines, with IC₅₀ values ranging between 3.1 and 19.μ M and shows similar levels of efficacy, but a different spectrum of activity, to cisplatin. Boxed in: Supramolecular boxes bind DNA, prevent DNA transactions and inhibit growth of cancer cells. The interaction of a 2,7-diazapyrenium-based ligand and its Pt^II rectangular metallacycle with native DNA (see scheme) was explored. The metallacycle is active against four human cancer cell lines, and shows similar levels of efficacy, but a different spectrum of activity, to cisplatin.