Tetra-2,3-pyrazinoporphyrazines with Externally Appended Pyridine Rings. 10. A Water-Soluble Bimetallic (ZnII/PtII) Porphyrazine Hexacation as Potential Plurimodal Agent for Cancer Therapy: Exploring the Behavior as Ligand of Telomeric DNA G-Quadruplex Structures

Abstract

The behavior of a bimetallic water-soluble (Zn(II)/Pt(II)) porphyrazine hexacation as ligand of G-quadruplex (G4) structures adopted by a human telomeric DNA sequence has been examined with different spectroscopic techniques. In K(+) rich solution the hexacationic Zn(II) porphyrazine ligand bearing a peripheral cis-platin-like functionality changes the G-quadruplex conformational equilibrium of the human telomeric sequence 5'-d[AGGG(TTAGGG)(3)]-3' and drives it exclusively toward a very stable parallel G4 form in the complex with 2:1 stoichiometry. An increase of the melting temperature of more than 20 °C is observed in this complex compared to the G4 alone. On the contrary ligand binding to G-quadruplex of the same telomeric sequence in Na(+) rich solution neither markedly influences the predominant basket conformation nor confers increased thermal stability to the G4 structure.