Antitumoral Gold and Silver Complexes with Ferrocenyl-Amide Phosphines

Abstract

The monosubstituted ferrocenyl-amide phosphine ligands PPh2CH2CH2NHCOFc and (PPh2CH2CH2)2NCOFc and the disubstituted ferrocenyl-amide diphosphine (PPh2CH2CH2NHCO)2Fc have been synthesized and used to prepare the gold chloride derivatives [AuCl­(PPh2CH2CH2NHCOFc)], [Au2Cl2{(PPh2CH2CH2)2NCOFc}], and [Au2Cl2{(PPh2CH2CH2NHCO)2Fc}] or the silver species [Ag­(OTf)­(PPh2CH2CH2NHCOFc)2] and [Ag­(OTf)­(PPh3)­(PPh2CH2CH2NHCOFc)]. In the gold complexes the chloro ligands can be easily substituted by several biologically relevant thiolates such as 2-mercaptonicotinic acid, 2-thiocytosine, 2-thiouracil, 2-mercaptopurine, and 2,3,4,6-tetra-6-acetyl-1-thiol-β-d-glucopyranosato, affording the gold phosphine thiolate derivatives. In addition, the gold phosphine thiolates of the closely related 1,1′-bis­(diphenylphosphine)­ferrocene ligand have been prepared in order to compare their biological activities. The antiproliferative activity of these compounds has been tested by the MTT viability assay in two murine cell lines, NIH-3T3 (mouse embryonic fibroblasts) and PC-12 (pheochromocytoma of the rat adrenal medulla), and two human cell lines, A-549 (adenocarcinomic human alveolar basal epithelial cells) and Hep-G2 (hepatocellular carcinoma). The amide-phosphine ligands are not active, whereas the chloro-gold derivatives have good antiproliferative activity in the murine cell lines and very low activity in the human cell lines. The silver complexes are less active than the gold derivatives. The gold thiolate complexes have moderate to very good cytotoxic activity for all of the ligands, showing excellent IC50 values for the thiolate complexes of the amide-phosphines PPh2CH2CH2NHCOFc and (PPh2CH2CH2N)2COFc and dppf.

Group 11 Metal Complexes with Unsymmetrical Bifunctional Ferrocene Ligands

“…C, H, and N analyses were performed with a Perkin-Elmer 2400 microanalyzer. The 1 H, 13 C{ 1 H}, 19 F, and 31 P{ 1 H} NMR spectroscopy, including 2D experiments, was performed with Bruker Avance 400 or Bruker ARX 300 spectrometers. Chemical shifts are reported relative to the solvent peaks [42] in the 1 H and 13 C spectra or external 85 % H 3 PO 4 in the 31 P spectra.…”

“…The 31 P{ 1 H} NMR spectra show one resonance at δ = 35 and 25 ppm for 1 and 2, respectively, significantly downfield relative to that of their precursor L1 (δ = -24 ppm), which confirms the coordination to the gold(I) center through the phosphorus atom. The 19 F NMR spectrum of 1 shows three signals corresponding to the ortho, meta, and para fluorine at-oms of the pentafluorophenyl ring. Both 1 and 2 were treated with other gold(I), silver(I), and copper(I) compounds to provide homo-or heteronuclear derivatives.…”

“…[38] The reaction of 6 and the silver(I) complex [Ag(OTf )(tht)] in an equimolecular ratio gives the heterodimetallic compound [AuAg(C 6 F 5 ) 3 (μ-{Fc(CH 2 PPh 2 )(PPh 2 )})(tht)]OTf (14) as an air-and moisture-stable yellow solid. The IR spectrum shows the absorptions arising from the trifluoromethanesulfonate anion at ν = 1281 [vs, br, ν as (SO 3 19 F NMR spectrum presents six resonances that correspond to the two types of pentafluorophenyl groups in a 2:1 ratio for the ortho, meta, and para fluorine atoms of each C 6 F 5 unit without significant differences to those for the precursor 6. The 31 P{ 1 H} NMR spectrum shows a multiplet at δ = 11.0 ppm for the P-Au III moiety and two doublets centered at δ = 1.9 ppm for the phosphorus atom coupled to both silver nuclei, 107 Ag and 109 Ag, with different coupling constants.…”

“…[1] Some of us have described the formation of several amidephosphines containing ferrocene units, studied their coordination chemistry, [17,18] and also showed that some gold and silver complexes are active as antitumor agents. [19] Herein, we report on the synthesis and characterization of a series of gold(I), gold(III), silver(I), and copper(I) derivatives with the racemic forms of two ferrocenyl phosphine ligands with planar chirality, namely, [Fc(CH 2 NMe 2 )(PPh 2 )] (L1) and [Fc(CH 2 PPh 2 )(PPh 2 )] (L2, Scheme 1).…”

Zinc(II) and Cadmium(II) Complexes of 5‐Ferrocenyl‐1H‐tetrazole: Synthesis, Structures, and Catalytic Effects on Thermal Decomposition of Energetic Compounds

“…[1][2][3][4][5][6][7][8][9][10][11] Moreover, ferrocene-based molecules that contain nitrogen-rich heterocyclic rings are very important ferrocene derivatives and function as versatile organometallic ligands. [12] Although coordination chemistry of a number of nitrogen-rich heterocyclic compounds bearing ferrocenyl groups has been extensively studied, coordination chemistry of 5-ferrocenyl-1H-tetrazole (HFcTz) has been less developed.…”