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Reaction of (tetraphenylchlorinato)iron() chloride with eight equivalents of tert-butyl isocyanide and 2,6-xylyl isocyanide in the presence of zinc amalgam afforded Fe(TPC)(t-BuNC) 2 1 and Fe(TPC)(2,6-xylylNC) 2 2, respectively. The synthesis and characterization of the trifluoromethanesulfonato derivatives of (tetraphenylchlorinato)iron() 3, bis(tert-butyl isocyanide)(tetraphenylchlorinato)iron() 4, and bis(2,6-xylyl isocyanide)(tetraphenylchlorinato)iron() 5 are reported:The 1 H NMR isotropic shifts at 20 ЊC of the pyrrole protons of the two complexes 4 and 5, varied from 5 ppm for 4 to 8 ppm for 5 rather than the expected Ϫ10 to Ϫ30 ppm, based on previously studied bis-ligated complexes of lowspin iron() chlorins. EPR spectra of [Fe(TPC)(t-BuNC) 2 ]CF 3 SO 3 4 in solution are axial, with g ⊥ = 2.15 and g || = 1.97 at 4 K, Σg 2 = 14.7. All physical properties are consistent with a low-spin iron() with an unusual ground-state configuration (d xz ,d yz ) 4 (d xy ) 1 .

Recently, Gold(III) porphyrins have gained great interest as anticancer drugs not only for stability of gold(III), but also for the functionalization of porphyrin to allow bridging with another metal such as platinum(II). We report here, for the first time, the synthesis of three new bi-metal compounds containing gold(III) porphyrin conjugated to a platinum diamine moiety through malonate bridging to obtain enhanced cytotoxicity from both metals combined to the phototoxicity of the porphyrin. The three complexes differ by type of diamine ligands around platinum(II) which are ammonia (NH3), cyclohexane diamine (CyDA) and pyridine methyl amine (Py). The synthesis was carried out using complexation of activated malonic acid derivatives with aqua diamino-platinum(II) complexes and the products were characterized by IR, NMR, mass spectra and by elementary analysis. Cytotoxic activity of the conjugates was screened in both healthy and cancer cell lines, human fibroblast cells (FS-68) and human breast cancer cells (MCF-7), and was compared to the corresponding platinum(II) complexes. The cyclohexyldiamine (CyDA) derivative exhibited the most cytotoxic effect among the series. The results showed that gold(III)/Pt(II)conjugates are more potent by 2 to 5.6-fold than the corresponding platinum complexes. Moreover, the dyad AuP-PtCyDA is 18% more potent and also more selective towards cancer cells than the parent gold porphyrin substituted with malonic acid. On the other hand, the IC50 of dyad AuP-PtCyDA is 43% lower than that of AuTPP, but more selective towards healthy cells. Singlet oxygen measurements indicated that gold(III) porphyrin derivatives are poor oxygen sensitizers and cell death occurred potentially due to generation of others reactive oxygen species (ROS) upon reductive quenching of the gold porphyrin excited state. In addition, the increase in cancer cell death obtained after light irradiation is totally absent in healthy cells, demonstrating the specificity of this PDT treatment on cancer cells. Our findings imply that the incorporation of two different cytotoxic metals in the same molecule represents a remarkable cytotoxic effect compared to traditional homometallic Pt(II) drugs.

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