Tetra-2,3-pyrazinoporphyrazines with externally appended pyridine rings. 9. Novel heterobimetallic macrocycles and related hydrosoluble hexacations as potentially active photo/chemotherapeutic anticancer agents

摘要

New homo- and heterobimetallic porphyrazine complexes of general formula [(M′Cl_2)LM] (L = tetrakis-2,3-[5,6-di-(2-pyridyl)pyrazino] porphyrazinato dianion), with M = Zn~(II), Mg~(II)(H _2O), or Pd~(II) in the central cavity and one M′Cl _2 unit (M′ = Pd~(II), Pt~(II)) peripherally coordinated at the pyridine N atoms of one of the dipyridinopyrazine fragments, were prepared and characterized by elemental analyses and IR/UV-visible spectroscopy. Related water-soluble salt-like species, carrying the hexacations [(PtCl_2)(CH_3)_6LM]~(6+) (neutralized by I- ions), were also prepared and similarly characterized. Retention of clathrated water molecules is a common feature of all the compounds. A detailed ~1H and ~(13)C NMR investigation in dimethylformamide (DMF-d_7) and dimethyl sulfoxide (DMSO-d_6) provided useful information on the type of arrangement in the neutral and hexacationic species of the metalated dipyridinopyrazine fragments, in which the metal centers (PdII/PtII) are bound to the pyridine N atoms ("py-py" coordination) with formation of N_(2(pyr))PdCl _2 or N2(pyr)PtCl_2 coordination sites, the latter one featuring a cis-platin-like functionality. Data obtained in DMF solution of the quantum yield (ΦΔ) for the generation of singlet oxygen, ~1O_2, the cytotoxic agent in photodynamic therapy (PDT), indicate that all the neutral and charged complexes, among them particularly those carrying centrally Zn~(II) or Pd~(II), exhibit excellent photosensitizing properties, this qualifying the externally platinated complexes as potential bimodal PDT/chemotherapeutic anticancer agents. Fluorescence data (Φ_F) provided additional information on the photoactivity of all the species studied. The following companion paper describes the observed interaction of the Zn~(II) hexacation [(PtCl _2)(CH_3)_6LZn]~(6+) with a G-quadruplex (G4) structure of the telomeric DNA sequence 5′-d[AGGG(TTAGGG) _3]-3′ in water.