Pentafluorophenyl Platinum(II) Complexes of PTA and Its N-Allyl and N-Benzyl Derivatives: Synthesis, Characterization and Biological Activity

Abstract

From the well-known 1,3,5-triaza-phosphaadamantane (PTA, <b>1a</b>), the novel N-allyl and N-benzyl tetrafuoroborate salts 1-allyl-1-azonia-3,5-diaza-7-phosphaadamantane (APTA(BF₄), <b>1b</b>) and 1-benzyl-1-azonia-3,5-diaza-7-phosphaadamantane (BzPTA(BF₄), <b>1c</b>) were obtained. These phosphines were then allowed to react with (Pt(μ-Cl)(C₆F₅)(tht))₂ (tht = tetrahydrothiophene) affording the water soluble Pt(II) complexes <i>trans-</i>(PtCl(C₆F₅)(PTA)₂) (<b>2a</b>) and its bis-cationic congeners <i>trans-</i>(PtCl(C₆F₅)(APTA)₂)(BF₄)₂ (<b>2b</b>) and <i>trans-</i>(PtCl(C₆F₅)(BzPTA)₂)(BF₄)₂ (<b>2c</b>). The compounds were fully characterized by multinuclear NMR, ESI-MS, elemental analysis and (for <b>2a</b>) also by single crystal X-ray diffraction, which proved the <i>trans</i> configuration of the phosphine ligands. Furthermore, in order to evaluate the cytotoxic activities of all complexes the normal human dermal fibroblast (NHDF) cell culture were used. The antineoplastic activity of the investigated compounds was checked against the human lung carcinoma (A549), epithelioid cervix carcinoma (HeLa) and breast adenocarcinoma (MCF-7) cell cultures. Interactions between the complexes and human serum albumin (HSA) using fluorescence spectroscopy and circular dichroism spectroscopy (CD) were also investigated.