Bifunctional Platinum Research Articles

Molybdenum oxycarbide hydrocarbon isomerization catalysts: cleaner fuels for the future

The catalytic behaviour of the molybdenum oxycarbide catalyst, synthesized in situ from molybdenum oxide, is compared with that of a supported bifunctional platinum catalyst for the isomerization of n-octane. The main products are the mono- and di-methyl isomers, and almost no aromatics are observed. It is shown that a high selectivity to the isomer products (> 90%) can be obtained over the molybdenum catalyst, even close to the thermodynamic equilibrium (i.e., at high conversion (75%)), while this is not possible over the platinum catalyst. Furthermore, the high resistance of the molybdenum catalyst to sulphur and nitrogen catalyst poisons typically found in crude oil is shown, and the isomerization of n-heptane over a supported molybdenum oxycarbide (MoO 3/SiC) catalyst is demonstrated.

DNA adducts of antitumor trans-[PtCl2 (E-imino ether)2

It has been shown recently that some analogues of clinically ineffective trans-diamminedichloroplatinum (II) (transplatin) exhibit antitumor activity. This finding has inverted the empirical structure-antitumor activity relationships delineated for platinum(II) complexes, according to which only the cis geometry of leaving ligands in the bifunctional platinum complexes is therapeutically active. As a result, interactions of trans platinum compounds with DNA, which is the main pharmacological target of platinum anticancer drugs, are of great interest. The present paper describes the DNA binding of antitumor trans-[PtCl(2)(E-imino ether)(2)] complex (trans-EE) in a cell-free medium, which has been investigated using three experimental approaches. They involve thiourea as a probe of monofunctional DNA adducts of platinum (II) complexes with two leaving ligands in the trans configuration, ethidium bromide as a probe for distinguishing between monofunctional and bifunctional DNA adducts of platinum complexes and HPLC analysis of the platinated DNA enzymatically digested to nucleosides. The results show that bifunctional trans-EE preferentially forms monofunctional adducts at guanine residues in double-helical DNA even when DNA is incubated with the platinum complex for a relatively long time (48 h at 37 degrees C in 10 mM NaCIO(4). It implies that antitumor trans-EE modifies DNA in a different way than clinically ineffective transplatin, which forms prevalent amount of bifunctional DNA adducts after 48 h. This result has been interpreted to mean that the major adduct of trans-EE, occurring in DNA even after long reaction times, is a monofunctional adduct in which the reactivity of the second leaving group is markedly reduced. It has been suggested that the different properties of the adducts formed on DNA by transplatin and trans-EE are relevant to their distinct clinical efficacy.

A novel DNA structure induced by the anticancer bisplatinum compound crosslinked to a GpC site in DNA.

The bifunctional platinum compound, [(trans-PtCI(NH)3)2)2(H2N(CH2)4NH2)]2+, forms a stable adduct with the self-complementary DNA oligomer CATGCATG, with the two platinum atoms coordinated at the N7 positions of the two symmetrical G4 nucleotides. The NMR-derived structure shows that the DNA octamer forms a novel hairpin structure with the platinated G4 residue adopting a syn conformation and the guanine base in the minor groove. Two such hairpins stack end-over-end and are linked together by the butanediamine tether to form a dumbbell structure. Such unusual structural distortion is different from that of the anticancer drug cisplatin-DNA adduct and may provide clues to explain the distinct biological activities of the two compounds.

Catalytic synthesis of C-alkylimidazoles over platinum-alumina catalysts

The synthesis of C-alkylimidazoles from 1,2-diamines and carboxylic acids over bifunctional platinum—alumina catalysts has been studied. It has been shown that this method is effective for the synthesis of 2-alkyl and 2,4-dialkylimidazoles including imidazoles with long-chain alkyls. The effect of the reaction temperature, space velocity of the flow of the raw materials, and dilution by hydrogen on the yield of product has been examined for the example of the synthesis of 2-methylimidazole from ethylenediamine and acetic acid, and the stability of the catalyst in continuous reaction cycles with intermediate oxidative regeneration has been studied. The composition of the accompanying products has been established and a mechanism proposed for their formation.

Unusual isomerization reaction of a platinum-dinucleotide compound

The reaction between a bifunctional platinum complex and nucleic acid base occurs via a two-step mechanism, and the first step is normally a preferential binding to the N7 site of a guanine. The present paper mainly describes results obtained about the second step, i.e., chelation after the first platinum binding. The reaction of [Pt,(R,R-dach)(OH 2 ) 2 ] 2+ with r(GpA) (abbreviations: R,R-dach, 1R,2R-cyclohexanediamine; r(GpA), guanylyl(3'-5')adenosine) results in interbase cross-linked compounds between the guanine and the adenine bases

Cytotoxicity of asymmetric platinum complexes against L-1210 cells. Effect of bulky substituents.

The asymmetric platinum complexes cis-Pt(LL')Cl2 (L = NH3, L' = CH3NH2, (CH3)2NH, C2H5NH2 and (C2H5)2NH and LL' = N,N-dimethylethylenediamine),--one of the NH3 groups of cis-Pt(NH3)2Cl2 was substituted by alkylamine--, were synthesized and their cytotoxic effects have been measured using L-1210 cells. The IC50 values of the asymmetric platinum complexes,--being obtained after 24 h exposure of L-1210 cells to the platinum complexes--, are almost comparable to the corresponding value of cis-Pt(NH3)2Cl2. In 2 h exposure, however, the IC50 values of the platinum complexes were dramatically changed, i.e., a marked difference was observed between those of L' = RNH2 and L' = R2NH. On the other hand, the amounts of platinum taken into the L-1210 cells is little affected by the alkylamino substitution. The results suggest that the bifunctional platinum binding to the target molecule may be responsible for the cytotoxicity.

The effect of platinum derivatives on interfacial properties of DNA.

The interaction of DNA modified by the binding of various platinum compounds with an electrically charged mercury surface was studied by means of linear sweep voltammetry. It was found that DNA and its adducts with antitumour active cis-diammine-dichloroplatinum(II) (cis-DDP) on the one hand and antitumour inactive trans-diamminedichloroplatinum(II) (trans-DDP) and diethylenetriaminechloroplatinum(II) chloride (dien-Pt) on the other were unwound due to their adsorption on the negatively charged mercury surface polarized to the potentials of a narrow region around -1.2 V (vs. saturated calomel electrode). The modification of DNA by bifunctional platinum compounds (cis- and trans-DDP) resulted in a substantial lowering of the extent of this interfacial conformational rearrangement, the modification by trans-DDP being more effective. The modification of DNA by monofunctional dien-Pt influenced the unwinding of DNA on the mercury surface only negligibly. It has been concluded that in particular interstrand cross-links induced by platinum compounds in DNA are responsible for the effect of these drugs on the extent of the interfacial unwinding of DNA. This conclusion is in good agreement with the view that among the lesions induced in DNA by platinum compounds, the interstrand cross-links are of less significance from the point of view of the antitumour efficacy of these inorganic drugs.

The interaction of aquated platinum(II) compounds with purine mononucleotides

The interactions of aquated bifunctional cis-diammineplatinum(II) and 2,2,N,N-tetramethylpropanediamineplatinum(II) and monofunctional diethylenetriamineplatinum(II) with 5′-GMP, 5′-IMP and 3′-GMP were investigated by 1H-NMR. Reaction of these aquated platinum compounds with a stoichiometric amount of the mononucleotide yields 1:1 Pt-nucleotide complexes as reaction products. The bifunctional platinum compounds containing one mononucleotide may react further with additional mononucleotides or with chloride to form 1:2 Pt-nucleotide complexes, or 1:1 Pt-nucleotide complexes in which a chloride is coordinated to platinum. Competition binding experiments show that both aquated cis-diammineplatinum and diethylenetriamineplatinum(II) bind preferentially to 5′-GMP when allowed to react with a mixture of 5′-GMP and 3′-GMP.

Activity and selectivity of bifunctional platinum catalysts in hydrocarbon reactions

Conversions of a number of C 6C 8-alkanes, naphthenes, and aromatics on bifunctional platinum/carrier catalysts, on Pt-black, and on the acidic carriers of the bifunctional catalysts are investigated in the temperature range 300–500 °C and at hydrogen partial pressures of 0–45 bars in a continuously operated fixed-bed reactor and in microcatalytic pulse reactors. Three activity and selectivity levels of the platinum in bifunctional Pt/acidic carrier catalysts may be broadly recognized: (1) temperatures below 350 °C where mainly platinum-catalyzed reactions contribute to the measured product distributions, (2) a temperature region around 400 °C where platinum drastically changes its activity and selectivity in hydrogenolysis and isomerization reactions due to removable carbonaceous deposits and (3) a region above about 400 °C where due to irreversible carbiding platinum only displays (de)hydrogenation activity. The product distributions from conversions of the model compounds on irreversibly carbided Pt/carrier catalysts are mainly governed by acid-catalyzed interconversions through nonclassical carbonium ion intermediates.