José R. Masaguer

Palladated and platinated complexes derived from phenylacetaldehyde thiosemicarbazone with cytotoxic activity in cis- DDP resistant tumor cells. Formation of DNA interstrand cross-links by these complexes

In the present paper we report the synthesis and characterization by 1H 13C NMR and heteronuclear 2D NMR spectroscopies of two new metallic complexes derived from phenylacetaldehyde thiosemincarbazone: Pt(C9H11N3S)Cl2, compound 2, and Pd(C9H11N3S)Cl2, compound 3. The testing of the cytotoxic activity of these compounds against several human and murine cell lines sensitive and resistant to cis-DDP suggests that compounds 2 and 3 may be considered potential anticancer agents since they exhibit 1C50 values in a microM range similar to cisplatin (cis-DDP). The cytotoxic activity of these compounds is higher in cis-DDP-resistant tumor cells than that of other antitumor drugs such as etoposide and adriamycin. On the other hand, the analysis of the interaction of compounds 2 and 3 with linear plasmid DNA indicate that both compounds, particularly compound 3, have an enhanced capacity to form DNA interstrand cross-links in comparison with cis-DDP.

Complexes of divalent nickel and copper with the Schiff base derived from 2-(2-aminophenyl)benzimidazole and benzaldehyde

SummaryThe reactions of divalent nickel and copper salts with the Schiff base derived from 2-(2-aminophenyl)benzimidazole and benzaldehyde, L, yield complexes of general formulae [CuL2X2] (X=Cl, Br, or ClO4), [CuL(SO4)], [CuL(SO4)] · 4H2O, and NiLX2 (X=Cl, Br, or NCS).All the complexes have been characterized by elemental analyses, magnetic measurements, e.s.r. electronic and i.r. spectral studies. The results show that the Schiff base acts as bidentate ligand through the pyridine-like imine nitrogen of imidazole ring and the azomethine nitrogen. Tentative structures of the complexes are suggested.

Binuclear chloro-bridged palladated and platinated complexes derived from p-isopropylbenzaldehyde thiosemicarbazone with cytotoxicity against cisplatin resistant tumor cell lines

Two novel dimeric chloro-bridged complexes [Pd (p-is. TSCN) (mu-Cl)]2, 2, and [Pt (p-is. TSCN)(mu-Cl)]2, 3, where p-is. TSCN = p-isopropylbenzaldehyde thiosemicarbazone, 1, have been synthesized and characterized by IR and NMR spectroscopy. The in vitro antitumor activity shown by both compounds against several human and murine cell lines sensitive and resistant to the clinically-used drug cisplatin (cis-DDP) suggests that compounds 2 and 3 may be endowed with important anticancer properties. Thus, compounds 2 and 3 not only show IC50 values in the microM range as cis-DDP but also display cytotoxic activity in tumor cell lines resistant to this drug. The analysis of the interaction of these binuclear p-is. TSCN compounds with DNA secondary and tertiary structures indicate that they form DNA interhelical cross-links, a biochemical property that may be involved in their mechanism of action.

Synthesis and characterization of copper(II) and nickel(II) complexes of the Schiff base derived from 2-(2-aminophenyl)benzimidazole and salicylaldehyde

SummaryCopper(II) and nickel(II) complexes with the Schiff base derived from 2-(2-aminophenyl)benzimidazole and salicylaldehyde, L, have been prepared. They are of the general types ML2X2 (M = Ni or Cu and X = Cl, Br, NO3 or ClO4) and NiL(NCS)2.The compounds have been characterized by elemental analyses, magnetic measurements, e.s.r., electronic and i.r. spectra studies. The i.r. spectra suggest that the molecule, and not the anion, of the Schiff base is coordinated as a bidentate ligand with the metal ion. Possible structures for the complexes have been proposed.

Pd(II) and Pt(II) Complexes of 2‐Phenyl‐ and 2‐Benzyl‐imidazoline: Synthesis, Structural Characterization, DNA Modification and in vitro Antileukaemic Activity

In this paper we describe the synthesis and chemical characterization of three new Pd(II)-imidazoline complexes: [PdCl 2 (C 6 H 5 -CH 2 -C 3 H 5 N 2 ) 2 ] (2), [PdCl(SEt 2 ) (C 6 H 4 -C 3 H s N 2 )] (5) and [Pd(C 6 H 4 -C 3 H 5 N 2 ) (μ-Br)] 2 (6). We have also analyzed the DNA modifications and in vitro antileukaemic activity of these compounds and of their previously reported analogs [Pd Cl 2 (C 6 H 5 -C 3 H 5 N 2 ) 2 ] (1), [Pd (C 6 H 4 -C 3 H 5 N 2 ) (μ-OAC)] 2 (3), [Pd (C 6 H 4 -C 3 H 5 N 2 ) (μ-Cl)] 2 (4) and [Pt(C 6 H 4 -C 3 H 5 N 2 )(μ-Cl] (7). All these compounds modify the DNA secondary structure since they alter the melting temperature (T m ) of the DNA. Circular dichroism spectra indicated, moreover, that compounds 3, 5 and 6 induced higher modification on the double helix than compounds 1, 2 and 4. While compounds 1, 2 and 5 seem to induce slight changes in the electrophoretic mobility of the open and covalently closed circular forms of pUC8 DNA at high r i (input molar ratio of Pd or Pt to nucleotides), compounds 3, 6 and 7 do not modify at any r i the tertiary structure of the plasmid DNA. Antileukaemic tests suggest that compounds 1, 4 and 7 exhibit important cytotoxic activity since their IC 50 values against HL-60 human leukaemic cells were below 10 μg ml -1 .

Complexes of 2-acetylpyridinesemicarbazone and 2-acetylpyridinethiosemicarbazone with cobalt(II), chromium(III) and copper(II)

SummaryThe synthesis and characterization of 2-acetylpyridine-semicarbazone (apsc) and 2-acetylpyridinethiosemicarbazone (aptsc) and their complexes with CoCl2, CrCl3 and CuCl2 are reported. These compounds were characterized on the basis of elemental analyses, electronic and i.r. spectra, magnetic moments and conductivity measurements. The molar conductivities in dimethyl formamide indicate the non-ionic nature of the metal chelates. An octahedral structure is proposed for the chromium(III) chelate-complexes, tetrahedral for the copper(II) compounds and tetrahedral or octahedral for the cobalt(II). Apsc and aptsc are bidentate but with different donors, though aptsc is monodentate in its complex with CrCl3.

Reactivity of acetate-bridged cyclopalladated complexes. 1H and 13C NMR studies of some monomeric derivatives of N-(4-methoxyphenyl)-α-benzoylbenzylideneamine

Abstract The reactions have been studied of acetate-bridged cyclopalladated complexes with different reagents to yield monomeric structures. The relative reactivity is even higher than that of the corresponding chloro- and bromo-dimers, usually obtained from the acetates and used as starting materials in bridge-cleavage reactions. The 1H and 13C NMR spectra of the monomeric complexes have allowed evaluation of the influence of the palladium on the chemical shifts of the surrounding nuclei. The slow crystallization of [{Pd(μ-Br)(4-MeOC6N4NC(COC6H5)C6H4)}2] from DMSO induces a bridge-splitting reaction to afford [Pd(4-MeOC6N4NC(COC6H5)C6H4)(DMSO)Br].

Iron―xanthate complexes [Fe(CO)2(η-C5R5){SC(S)OEt}] and [Fe(CO)-(η-C5R5)(S2COEt)] (R = H or Me). Synthesis and electrochemistry

Xanthate complexes of the type [Fe(CO)2(η-C5R5){SC(S)OEt}][R = H (1) or Me (2)] can be conveniently prepared by reaction between [{Fe(CO)2(η-C5R5)}] and [SC(S)OEt]2 in cyclohexane. U.v. photolysis of (1) and (2) causes decarbonylation and affords the chelate complexes [Fe(CO)(η-C5R5)(S2COEt)][R = H (3) or Me (4)]. The electrochemical behaviour of these complexes has been studied both in acetonitrile and dichloromethane using cyclic voltammetry and coulometry. The monocarbonyl complexes (3) and (4) in dichloromethane exhibit a reversible oxidation–reduction process. In acetonitrile the oxidation reaction is accompanied by the co-ordination of solvent. The multicyclic voltammograms of the dicarbonyl complexes (1) and (2), in both solvents, reveal that the oxidation is followed by elimination of one molecule of carbon monoxide from iron, affording the corresponding chelate complexes (3) and (4).

Cyclopentadienyl iron xanthate complexes. Crystal and molecular structure and electrochemical reduction of η-C5R5Fe(CO)2(η1-SC(S)OEt) (RH or CH3)

Abstract Complexes η-C5R5Fe(CO)2(η1-SC(S)OEt) (RH, (1) and RCH3 (2)) have been analysed by X-ray diffraction techniques. 1: P212121 11.3560(5), 10.8595(4), 10.1158(3) A, Z=4; 1023 observed reflexions, R and Rw 0.069 and 0.073. 2: Pbca, 15.6907(11), 15.4566(13), 14.3083(11) A, Z=8; 2271 observed reflexions, R and Rw being 0.071, 0.073. The coordination is quite similar for both compounds with the xanthate monodentate ligand almost perpendicular to the ring planes and a relative twist, one from each other of about 10°. The reductive electrochemistry of both complexes has been examined by cyclic voltammetry and coulometry. In a carbon electrode the first-one electron reduction step can be ascribed to the formation of corresponding carbonyl dimers. In a mercury electrode, the first reduction step of 1 leads to a bond rupture process with formation of a mercury compound [CpFe(CO)2]2Hg and further reduction to the anion CpFe(CO)2−. However, the behaviour of the pentamethylcyclopentadienyl complex (2) is quite different, and it is reduced in a three step process.

Reaction of folded acetate-bridged ortho-palladated complexes with CH2Cl2. Crystal structure of[{Pd(C6H5 CH2 N C (COC6H5) C6H4)(μ-Cl)}2]

Abstract Folded acetate-bridged ortho -palladated complexes of benzoylbenzylideneamines react with CH 2 Cl 2 to afford unfolded chlorobridged ortho -palladated complexes. This finding is supported by an X-ray crystallographic study of the complex [{Pd(C 6 H 5 CH 2  NC(COC 6 H 5 )C 6 H 4 )(μ-Cl)} 2 ].