Tetra-2,3-pyrazinoporphyrazines with externally appended pyridine rings. 12. New heteropentanuclear complexes carrying four exocyclic cis-platin-like functionalities as potential bimodal (PDT/Cis-platin) anticancer agents

摘要

Heteropentanuclear porphyrazines having the formula [(PtCl _2) _4LM] where L = tetrakis-2,3-[5,6-di(2-pyridyl)pyrazino] porphyrazinato dianion and M = Zn ~(II0, Mg ~(II)(H 2O), Pd ~(II), Cu ~(II) or Co ~(II) were characterized by elemental analyses, IR-UV-visible spectroscopy and electrochemistry and the data compared to new and previously published results for the corresponding homopentanuclear compound [(PtCl _2) _4LPt]. This latter species has four external N _(2(py))PtCl _2 coordination sites which closely resemble cis-platin, (NH _3) _2PtCl _2, the potent chemotherapeutic anticancer drug, and is able to act as a photosensitizer for the generation of ~1O _2, the cytotoxic agent in photodynamic therapy (PDT). UV-visible spectra and half wave potentials for reduction of [(PtCl _2) _4LM], [(PtCl _2) _4LPt], the parallel series of mononuclear [LM] compounds and the pentanuclear [(PdCl _2) _4LM] compounds were examined in the nonaqueous solvents dimethyl sulfoxide, pyridine, and dimethylformamide. The complete set of available data indicate that external coordination of the PtCl _2 and PdCl _2 units significantly increases the level of the electron-deficiency of the entire molecular framework despite the fact that these groups are far away from the central porphyrazine π-ring system and have coordination sites nearly orthogonal to the plane of the macrocycle. The pentanuclear species [(M'Cl _2) _4LM] (M' = Pt ~(II), Pd ~(II)) undergo multiple one-electron transfers and exhibit an easier reducibility as compared to related electrode reactions of the parent compounds [LM] having the same central metal. Aggregation phenomena and reducibility of the porphyrazines to their monoanionic form (prevalently in DMF) are observed for some of the examined compounds and were analyzed and accurately taken into account. Quantum yields of ~1O _2 (Φ; _Δ), of interest in PDT, were measured for [(PtCl 2) 4LM] with M = Zn ~(II), Mg ~(II)(H _2O), or Pd ~(II) and the related macrocycles [(PdCl _2) _4LM] and [LM] in dimethylformamide (DMF) and/or DMF preacidified with HCl (DMF/HCl, [HCl]: 1-2 × 10 ~(-4) M). Excellent Φ; Δ values (0.5-0.6) which qualify the compounds as potent photosensitizers in PDT were obtained for the pentanuclear species having Zn ~(II) or Pd ~(II) as central metal ions. The [(PtCl _2) _4LZn] and [(PtCl _2) _4LPd] complexes are of special interest as potential bimodal anticancer agents because of the incorporated four cis-platin-like functionalities.