DNA binding and antitumor activities of zinc(II) complexes with some S-alkenyl derivatives of thiosalicylic acid

Transition Metal Chemistry - Two zinc(II) complexes with S-alkenyl derivatives of thiosalicylic acid as ligands have been synthesized and characterized by microanalysis, IR, 1H and 13C NMR...     

DNA binding,antibacterial and antifungal activities of copper(II) complexes with some S-alkenyl derivatives of thiosalicylic acid

The biological activities of two binuclear copper(II) complexes containing S-alkenyl derivatives of thiosalicylic acid are reported [alkenyl = propenyl (L1), isobutenyl (L2)]. The structure of the complex with the S-isobutenyl derivative (C2) was confirmed by single-crystal X-ray structure analysis, which revealed that the structure consists of centrosymmetric, dinuclear complex molecules [Cu₂(S-i-butenyl-thiosal)₄(DMSO)₂] containing two Cu(II) centers bridged by four S-isobutyl-thiosalicylate ligands in a paddle-wheel type structure. The Cu(II) atom is situated in a distorted square-pyramidal environment formed by carboxylate oxygen atoms in the basal plane and a DMSO ligand in the axial position. The reactivities of the complexes toward guanosine-5′-monophosphate (5′-GMP) were investigated. Complex C2 ([Cu₂(S-i-butenyl-thiosal)₄(H₂O)₂]) reacted more rapidly with 5′-GMP than complex C1. The interactions of complexes C1 and C2 with calf thymus DNA (CT-DNA) were examined by absorption (UV–Vis) and emission spectral studies (ethidium bromide displacement studies), revealing good DNA interaction abilities. The antimicrobial activities of the free ligands and their complexes were tested by microdilution method, and both minimal inhibitory and microbicidal concentrations were determined. All the tested substances demonstrated selective and moderate antibacterial activity on gram-positive bacteria, but low antibacterial activity on gram-negative bacteria. Also, the tested substances demonstrated low antifungal activity.     

S-alkyl and S-alkylaryl cysteine complexes with platinum(II) and their interactions with nucleosides

The reactions of K₂PtCl₄ with the aminoacids, S-methyl-L-cysteine, S-ethyl-L-cysteine, S-benzyl-L-cysteine, S-para-nitro-benzyl-L-cysteine, S-diphenyl-methyl-L-cysteine, S-tribenzyl-L-cysteine and S-4′,4′-dimethoxy-diphenylmethyl-L-cysteine were studied in neutral or acidic aqueous solutions. Complexes of the formulae PtLCl₂, [PtL₂]Cl₂ and Pt(L-H⁺)₂, where L = aminoacid, were isolated in the solid state and their structures investigated with elemental analysis, conductivity measurements, IR, ¹H NMR and ¹³CNMR spectra. The results show that the coordination sites of Pt(II) with the amino-acids are the N and S atoms, producing two diastereoisomers around the chiral sulphur atom, which were identified in the ¹H NMR and ¹³CNMR spectra. The complexes PtLCl₂ further react with the nucleosides guanosine and inosine. The complexes [PtL(nucl)₂]Cl₂ were isolated from these reactions and studied with the same methods. They showed a PtN₇ bonding with the nucleosides and retained the N, S bondings with the aminoacids. As a result of the higher trans influence of S than N, the nucleoside molecule coordinated to the metal through N₇ and trans to S has a weaker bond strength than the other, as it is revealed from the ¹H NMR and ¹³C NMR spectra of these complexes.     

Quantitative structure activity relationships for some antitumor platinum(II) complexes

The INDO–SCF method is used to provide electronic indices which are used as independent variables. These attempt to account for the variation in the antitumor activity and toxicity observed within a series of analogs of cis-diamino dichloro platinum(II).     

Palladium(II) and platinum(II),(IV) complexes of 2-aminopyrimidine derivatives

Palladium(II) and Platinum(II),(IV) complexes with 2-aminopyrimidine derivatives (L1)–(L3), prepared by reacting the corresponding metal halide with the ligand in the required stoichiometric ratio, were characterised by chemical analyses and physical measurements. The structures have been assigned on the basis of i.r. spectroscopy, electronic reflectance spectra and molar conductivities.     

Importance of platinum(II)-assisted platinum(IV) substitution for the oxidation of guanosine derivatives by platinum(IV) complexes

Guanosine derivatives with a nucleophilic group at the 5' position (G-5') are oxidized by the Pt (IV) complex Pt( d, l)(1,2-(NH 2) 2C 6H 10)Cl 4 ([Pt (IV)(dach)Cl 4]). The overall redox reaction is autocatalytic, consisting of the Pt (II)-catalyzed Pt (IV) substitution and two-electron transfer between Pt (IV) and the bound G-5'. In this paper, we extend the study to improve understanding of the redox reaction, particularly the substitution step. The [Pt (II)(NH 3) 2(CBDCA-O,O')] (CBDCA = cyclobutane-1,1-dicarboxylate) complex effectively accelerates the reactions of [Pt (IV)(dach)Cl 4] with 5'-dGMP and with cGMP, indicating that the Pt (II) complex does not need to be a Pt (IV) analogue to accelerate the substitution. Liquid chromatography/mass spectroscopy (LC/MS) analysis showed that the [Pt (IV)(dach)Cl 4]/[Pt (II)(NH 3) 2(CBDCA-O,O')]/cGMP reaction mixture contained two Pt (IV)cGMP adducts, [Pt (IV)(NH 3) 2(cGMP)(Cl)(CBDCA-O,O')] and [Pt (IV)(dach)(cGMP)Cl 3]. The LC/MS studies also indicated that the trans, cis-[Pt (IV)(dach)( (37)Cl) 2( (35)Cl) 2]/[Pt (II)(en)( (35)Cl) 2]/9-EtG mixture contained two Pt (IV)-9-EtG adducts, [Pt (IV)(en)(9-EtG)( (37)Cl)( (35)Cl) 2] and [Pt (IV)(dach)(9-EtG)( (37)Cl)( (35)Cl) 2]. These Pt (IV)G products are predicted by the Basolo-Pearson (BP) Pt (II)-catalyzed Pt (IV)-substitution scheme. The substitution can be envisioned as an oxidative addition reaction of the planar Pt (II) complex where the entering ligand G and the chloro ligand from the axial position of the Pt (IV) complex are added to Pt (II) in the axial positions. From the point of view of reactant Pt (IV), an axial chloro ligand is thought to be substituted by the entering ligand G. The Pt (IV) complexes without halo axial ligands such as trans, cis-[Pt(en)(OH) 2Cl 2], trans, cis-[Pt(en)(OCOCF 3) 2Cl 2], and cis, trans, cis-[Pt(NH 3)(C 6H 11NH 2)(OCOCH 3) 2Cl 2] ([Pt (IV)(a,cha)(OCOCH 3) 2Cl 2], satraplatin) did not react with 5'-dGMP. The bromo complex, [Pt (IV)(en)Br 4], showed a significantly faster substitution rate than the chloro complexes, [Pt (IV)(en)Cl 4] and [Pt (IV)(dach)Cl 4]. The results indicate that the axial halo ligands are essential for substitution and the Pt (IV) complexes with larger axial halo ligands have faster rates. When the Pt (IV) complexes with different carrier ligands were compared, the substitution rates increased in the order [Pt (IV)(dach)Cl 4] < [Pt (IV)(en)Cl 4] < [Pt (IV)(NH 3) 2Cl 4], which is in reverse order to the carrier ligand size. These axial and carrier ligand effects on the substitution rates are consistent with the BP mechanism. Larger axial halo ligands can form a better bridging ligand, which facilitates the electron-transfer process from the Pt (II) to Pt (IV) center. Smaller carrier ligands exert less steric hindrance for the bridge formation.     

Thermal and spectral studies of palladium(II) and platinum(IV) complexes with dithiocarbamate derivatives

Four new coordination complexes of palladium(II) and platinum(IV) starting from bis(dimethylthiocarbamoyl)sulphide (L¹) and bis(diethylthiocarbamoyl)disulphide (L²) were synthesized and characterized in solid state by elemental analysis, infrared and electronic spectroscopy as well as thermal analysis (TG/DTA). The complexes were formulated on the basis of experimental data as [Pd(Me₂NCS₂)₂] (1), [Pt(Me₂NCS)₂SCl₄]·3H₂O (2), [Pd(Et₂NCS₂)₂] (3) and [Pt(Et₂NCS)₂S₂Cl₄]·4H₂O (4), respectively. TG experiments revealed the nature of complex species as hydrated (2 and 4) or anhydrous (1 and 3). Thermal decomposition of coordinated organic ligands occurs in one or two exothermic stages, the final residue being in all cases the free metal (Pd or Pt).     

Synthesis and mesomorphic properties of some platinum(II) and oxovanadium(IV) complexes

The synthesis and mesomorphic properties of a homologous series of N-(2-hydroxy-4-n-alkoxybenzylidene)-4'-n-decylphenylanilines and their platinum(II) and oxovanadium(IV) complexes are reported. All the ligands and their metal chelates exhibit enantiotropic mesophases, predominantly smectic A and smectic C phases. The transition temperatures and enthalpies have been determined for most of the compounds. The platinum(II) complexes have higher melting points and mesophase thermal stabilities. However, the oxovanadium(IV) complexes have a wider thermal range for the mesophase. Both platinum(II) and oxovanadium(IV) complexes containing only a chain on the biphenyl moiety exhibit a nematic phase.     

Cobalt(II), copper(II), zinc(II)—Amino and thiosalicylic acids ternary complexes

A series of Co(II), Cu(II), Zn(II)-thiosalicylic-amino acids of the molecular formula (M-TSA-a.a.) · 2 H₂O has been synthesized and characterized by chemical analyses, molar conductance, electronic and i.r. spectral measurements.     

Synthesis and antitumor properties of new platinum(IV) complexes with aminonitroxyl radicals

Acylation of cis,trans,cis-Pt^IV(RNH₂)(NH₃)(OH)₂Cl₂ with acetic anhydride afforded complexes cis,trans,cis-Pt^IV(RNH₂)(NH₃)(OAc)₂Cl₂, where R is 2,2,6,6-tetramethyl-1-oxylpiperidin-4-yl (1b) or 2,2,5,5-tetramethyl-1-oxylpyrrolidin-3-yl (2b). The complexes were characterized by elemental analysis, HPLC, and IR, UV, and ESR spectra. Complex 1b exhibits high antitumor activity comparable with that of Cisplatin against leukemia P388 used as the experimental tumor. Simultaneous administration of low doses of 1b and Cisplatin (1/20 of LD₅₀ each) results in synergism of the antitumor activity and 100% cure of animals. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 60–63, January, 2006.     

Synthesis and antitumor activity of DNA binding cationic porphyrin-platinum(II) complexes

A new series of DNA binding 5,10,15-tri(N-methyl-4-pyridiniumyl)porphyrin (TrisMPyP)-platinum(II) conjugates was synthesized, in which different spacer ligands were used for appropriate coordination to platinum(II) complexes. Compound 9b exhibited in vivo antitumor activity (T/C%, 294) superior to cisplatin (T/C%, 184) against the leukemia L1210 cell line.     

Luminescent cyclometalated platinum(II) complexes with amino acid ligands for protein binding

Pt(C/N)(phe)(1, C/N = 2-(2'-thienyl)pyridine, phe = phenylalanine) shows a high binding affinity (ca. 10(6) dm(3) mol(-1)) and selectivity towards human serum albumin (HSA) and such binding is accompanied by an enhancement of photoluminescence at 562 nm; both the protein binding affinity and cytotoxicities of [Pt(C/N)(phe)(1), Pt(C/N)(trp)(2, trp = tryptophan) and Pt(C/N)(gly)(3, gly = glycine)] are affected by the amino acid ligand with having an IC(50) of up to 1 microM against a number of carcinoma cell lines.     

Triamine-type complexes of platinum(II) and their antitumor properties

Triamines of platinum(II) (Pt(NH₃)₂LCl]Cl with a cis-structure (L represents cytosine, cytidine, isocytosine, theobromine, theophylline) and cis- and trans-isomers with theophylline and inosine were synthesized. The coordination formulas were demonstrated by methods of conductometry and long-wave spectroscopy. The coordination of pyrimidines through the N(3) atoms and purines through the N(7) atoms was established by PMR methods. An intensification of the acidic properties of the NH group of the ligands upon coordination with platinum was demonstrated. Cis-triamines have an antitumor effect on solid tumors and leukemias, which permits them to be assigned to a new class of water-soluble cationic monofunctional antitumor complexes of platinum(II).Leningrad Chemicopharmacological Institute. Translated from Teoreticheskaya i Éksperimental'naya Khimiya, No. 3, pp. 354–361, May–June, 1991. Original article submitted March 11, 1991.     

Synthesis,characterization, and antitumor activities of two copper(II) complexes with pyrazole derivatives

Two mononuclear copper(II) complexes with pyrazole derivatives, 1,1′-(anthracen-9-ylmethylene)bis(1H-pyrazole) (L¹ ) and 9-(4-(di(1H-pyrazol-1-yl)methyl)phenyl)-9H-carbazole (L² ), of formulae [CuL¹(CH₃CN)₂](ClO₄)₂ (1) and [CuL²(CH₃CN)₂](ClO₄)₂ (2) were prepared. Both complexes were confirmed by IR, MS, ¹H NMR, and elemental analyses. Complex 1 was also characterized by X-ray crystallography, confirming that copper(II) is coordinated by four nitrogen atoms from two L¹ and two oxygen atoms from two perchlorates. Furthermore, all ligands and complexes were tested in vitro for their antitumor activities using mouse melanoma cell line B16-F10, HepG2 human hepatoma cell line, and A549 human lung adenocarcinoma cell line. Both complexes displayed potent cytotoxicity and are promising substrates for further investigations.     

New palladium(II) and platinum(II) complexes with the model nucleobase 1-methylcytosine: antitumor activity and interactions with DNA

Palladium and platinum complexes with the model nucleobase 1-methylcytosine (1-Mecyt) of the types [Pd(N-N)(C6F5)(1-Mecyt)]ClO4 [N-N = bis(3,5-dimethylpyrazol-1-yl)methane (bpzm), bis(pyrazol-1-yl)methane (bpzm), N,N,N',N'-tetramethylethylenediamine (tmeda), or 2,2'-bipyridine (bpy)] and [M(dmba)(L')(1-Mecyt)]ClO4 [dmba = N,C-chelating 2-(dimethylaminomethyl)phenyl; L' = PPh(3) (M = Pd or Pt), DMSO (M = Pt)] have been obtained. Palladium and platinum complexes of the types cis-[M(C6F5)2(1-Mecyt)2] (M = Pd or Pt) and cis-[Pd(L')(C6F5)(1-Mecyt)2]ClO4 (L' = PPh(3) or t-BuNC) have also been prepared. The crystal structures of [Pd(bpzm)(C6F5)(1-Mecyt)]ClO4, [Pt(dmba)(DMSO)(1-Mecyt)]ClO4, cis-[Pd(C6F5)2(1-Mecyt)2], and cis-[Pd(t-BuNC)(C6F5)(1-Mecyt)2]ClO4 have been established by X-ray diffraction. There is extensive hydrogen bonding (N-H...O, C-H...F or C-H...O) in all the compounds. There are also intermolecular pi-pi interactions between pyrimidine rings of adjacent chains in [Pd(C6F5)2(1-Mecyt)2]. DNA adduct formation of the new complexes synthesized was followed by circular dichroism and electrophoretic mobility. Atomic force microscopy images of the modifications caused by the complexes on plasmid DNA pBR322 were also obtained. Values of IC(50) were also calculated for the new complexes against the tumor cell line HL-60. At a short incubation time (24 h) almost all new complexes were more active than cisplatin.     

The thermal decomposition of platinum(II) and (IV) complexes

The decomposition characteristics of Pt(II) and Pt(IV) complexes in hydrogen, air and argon were investigated by thermal gravimetric and differential thermal analysis. Based on weight-loss measurements, the thermal stability in hydrogen increased in the order: hexachloroplatinic acid<platinum acetyl acetonate<platinum diamino dinitrite<tetrammine platinous hydroxide<tetrammine platinous chloride<platinum phthalocyanine; whereas in air, the order was: hexachloroplatinic acid<tetrammine platinous hydroxide<platinum acetyl acetonate<platinum diamino dinitrite<tetrammine platinous chloride. The platinum complexes were more stable in air than in hydrogen where decomposition was observed in all platinum samples at temperatures below 200°C.     

Palladium(II) and platinum(II) dichloro complexes containing diamine-estrone derivatives

The preparation ofcis-dichloro Pt(II) andcis-dichloro Pd(II) complexes ofN-[3-hydroxyestra 1:3:5 (10)trien-17β]ethylendiamine,N-[3-hydroxyestra 1:3:5 (10)trien-17β]1,3-propylendiamine, andN-[3-hydroxyestra 1:3:5 (10)trien-17β]2-aminomethylpyridine is reported. The complexes have been characterized by chemical analysis, infrared spectroscopy and molar conductivity.