Mechanisms of substitution reactions on cyclometallated platinum(IV) complexes: "Quasi-labile" systems

The substitution reactions of SMe2 by phosphines (PMePh2, PEtPh2, PPh3, P(4-MeC6H4)(3), P(3-MeC6H4)(3), PCy3) on Pt-IV complexes having a cyclometalated imine ligand, two methyl groups in a cis-geometrical arrangement, a halogen, and a dimethyl sulfide as ligands, [Pt(CN)(CH3)(2)(X)(SMe2)], have been studied as a function of temperature, solvent, and electronic and steric characteristics of the phosphines and the X and CN ligands. In all cases, a limiting dissociative mechanism has been found, where the dissociation of the SMe2 ligand corresponds to the rate-determining step. The pentacoordinated species formed behaves as a true pentacoordinated Pt-IV compound in a steady-state concentration, given the solvent independence of the rate constant. The X-ray crystal structures of two of the dimethyl sulfide complexes and a derivative of the pentacoordinate intermediate have been determined. Differences in the individual rate constants for the entrance of the phosphine ligand can only be estimated as reactivity ratios. In all cases an effect of the phosphine size is detected, indicating that an associative step takes place from the pentacoordinated intermediate. The nature of the (CN) imine and X ligands produces differences in the dimethyl sulfide dissociation reactions rates, which can be quantified by the corresponding DeltaS double dagger values (72, 64, 48, 31, and 78 J K-1 mol(-1) for CN/X being C6H4CHNCH2C6H5/Br, C6H4CHNCH2-(2,4,6-(CH3)(3))C6H2/Br, C6H4CHNCH2C6H5/Cl, C6Cl4CHNCH2C6H5/Cl, and C6W4CH2NCHC6H5/ Pr, respectively). As a whole, the donor character of the coordinated C-aromatic and X atoms have the greatest influence on the dissociativeness of the rate-determining step.

The electrochemical reduction of the purines guanine and adenine at platinum electrodes in several room temperature ionic liquids

The reduction of guanine was studied by microelectrode voltammetry in the room temperature ionic liquids (RTILs) N-hexyltriethylammonium bis (trifluoromethanesulfonyl) imide [N6,2,2,2][N(Tf)2], 1-butyl-3-methylimidazolium hexafluorosphosphate [C4mim][PF6], N-butyl-N-methyl-pyrrolidinium bis(trifluoromethanesulfonyl)imide [C4mpyrr][N(Tf)2], 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide [C4mim][N(Tf)2], N-butyl-N-methyl-pyrrolidinium dicyanamide [C4mpyrr][N(NC)2] and tris(P-hexyl)-tetradecylphosphonium trifluorotris(pentafluoroethyl)phosphate [P14,6,6,6][FAP] on a platinum microelectrode. In [N6,2,2,2][NTf2] and [P14,6,6,6][FAP], but not in the other ionic liquids studied, guanine reduction involves a one-electron, diffusion-controlled process at very negative potential to produce an unstable radical anion, which is thought to undergo a dimerization reaction, probably after proton abstraction from the cation of the ionic liquid. The rate of this subsequent reaction depends on the nature of the ionic liquid, and it is faster in the ionic liquid [P14,6,6,6][FAP], in which the formation of the resulting dimer can be voltammetrically monitored at less negative potentials than required for the reduction of the parent molecule. Adenine showed similar behaviour to guanine but the pyrimidines thymine and cytosine did not; thymine was not reduced at potentials less negative than required for solvent (RTIL) decomposition while only a poorly defined wave was seen for cytosine. The possibility for proton abstraction from the cation in [N6,2,2,2][NTf2] and [P14,6,6,6][FAP] is noted and this is thought to aid the electrochemical dimerization process. The resulting rapid reaction is thought to shift the reduction potentials for guanine and adenine to lower values than observed in RTILs where the scope for proton abstraction is not present. Such shifts are characteristic of so-called EC processes where reversible electron transfer is followed by a chemical reaction. © 2009 Elsevier B.V.

Reaction intermediates of ethanol electro-oxidation on platinum investigated by SFG spectroscopy

Although electrochemical oxidation of simple organic molecules on metal catalysts is the basic ingredient of fuel cells, which have great technological potential as a renewable source of electrical energy, the detailed reaction mechanisms are in most cases not completely understood. Here, we investigate the ethanol-platinum interface in acidic aqueous solution using infrared-visible sum frequency generation (SFG) spectroscopy and theoretical calculations of vibrational spectra in order to identify the intermediates present during the electro-oxidation of ethanol. The complex vibrational spectrum in the fingerprint region imply on the coexistence of several adsorbates. Based on spectra in ultra-high-vacuum (UHV) and electrochemical environment from the literature and our density functional theory (DFT) calculations of vibrational spectra, new adsorbed intermediates, never before observed with conventional infrared (IR) spectroscopy, are proposed here: g2-acetaldehyde, g2-acetyl, ethylidyne, monodentate acetate, methoxy, tertiary methanol derivative, COH residue, g2-formaldehyde, mono and bidentate formate, CH3 and CH2 residues. In addition, we present new evidences for an ethoxy intermediate, a secondary ethanol derivative and an acetyl species, and we confirm the presence of previously observed adsorbates: a tertiary ethanol derivative, bidentate acetate, and COad. These results indicate that the platinum surface is much more reactive, and the reaction mechanism for ethanol electro-oxidation is considerably more complex than previously considered. This might be also true for many other molecule-catalyst systems.

Recovery of palladium from a spent automobile catalyst leaching solution by a thiodiglycolamide derivative

In the sequence of previous research on the development of novel liquid-liquid amidetype compounds to efficiently and selectively extract platinum-group metals (PGMs) from concentrated hydrochloric acid media, a specific thiodiglycolamide derivative – N,N’-dimethyl-N,N’-dicyclohexylthiodiglycolamide (DMDCHTDGA) – has been applied for the recovery of palladium(II) from a spent automobile catalyst leaching solution, containing palladium(II) and rhodium(III) as PGMs. The results obtained are rather promising, since the DMDCHTDGA behavior towards the two PGMs is similar to that observed for hydrochloric acid aqueous media studied before, simulating the real leaching phases. Within eleven metal elements co-existing in solution, the majority in high fold-excesses, only aluminum(III) and cerium(III) interfere in the palladium(II) liquid-liquid extraction process, requiring further optimization.

Egfr Activating Mutations And Their Association With Response To Platinum-doublet Chemotherapy In Brazilian Non-small Cell Lung Cancer Patients.

The aim of the study was to analyze the frequency of epidermal growth factor receptor (EGFR) mutations in Brazilian non-small cell lung cancer patients and to correlate these mutations with response to benefit of platinum-based chemotherapy in non-small cell lung cancer (NSCLC). Our cohort consisted of prospective patients with NSCLCs who received chemotherapy (platinum derivates plus paclitaxel) at the [UNICAMP], Brazil. EGFR exons 18-21 were analyzed in tumor-derived DNA. Fifty patients were included in the study (25 with adenocarcinoma). EGFR mutations were identified in 6/50 (12 %) NSCLCs and in 6/25 (24 %) adenocarcinomas; representing the frequency of EGFR mutations in a mostly self-reported White (82.0 %) southeastern Brazilian population of NSCLCs. Patients with NSCLCs harboring EGFR exon 19 deletions or the exon 21 L858R mutation were found to have a higher chance of response to platinum-paclitaxel (OR 9.67 [95 % CI 1.03-90.41], p = 0.047). We report the frequency of EGFR activating mutations in a typical southeastern Brazilian population with NSCLC, which are similar to that of other countries with Western European ethnicity. EGFR mutations seem to be predictive of a response to platinum-paclitaxel, and additional studies are needed to confirm or refute this relationship.

The Applicability Of Ordered Mesoporous Sba-15 And Its Hydrophobic Glutaraldehyde-bridge Derivative To Improve Ibuprofen-loading In Releasing System.

The mesoporous SBA-15 silica with uniform hexagonal pore, narrow pore size distribution and tuneable pore diameter was organofunctionalized with glutaraldehyde-bridged silylating agent. The precursor and its derivative silicas were ibuprofen-loaded for controlled delivery in simulated biological fluids. The synthesized silicas were characterized by elemental analysis, infrared spectroscopy, (13)C and (29)Si solid state NMR spectroscopy, nitrogen adsorption, X-ray diffractometry, thermogravimetry and scanning electron microscopy. Surface functionalization with amine containing bridged hydrophobic structure resulted in significantly decreased surface area from 802.4 to 63.0 m(2) g(-1) and pore diameter 8.0-6.0 nm, which ultimately increased the drug-loading capacity from 18.0% up to 28.3% and a very slow release rate of ibuprofen over the period of 72.5h. The in vitro drug release demonstrated that SBA-15 presented the fastest release from 25% to 27% and SBA-15GA gave near 10% of drug release in all fluids during 72.5 h. The Korsmeyer-Peppas model better fits the release data with the Fickian diffusion mechanism and zero order kinetics for synthesized mesoporous silicas. Both pore sizes and hydrophobicity influenced the rate of the release process, indicating that the chemically modified silica can be suggested to design formulation of slow and constant release over a defined period, to avoid repeated administration.

Platinum Blue Staining Of Cells Grown In Electrospun Scaffolds.

Fibroblast cells grown in electrospun polymer scaffolds were stained with platinum blue, a heavy metal stain, and imaged using scanning electron microscopy. Good contrast on the cells was achieved compared with samples that were gold sputter coated. The cell morphology could be clearly observed, and the cells could be distinguished from the scaffold fibers. Here we optimized the required concentration of platinum blue for imaging cells grown in scaffolds and show that a higher concentration causes platinum aggregation. Overall, platinum blue is a useful stain for imaging cells because of its enhanced contrast using scanning electron microscopy (SEM). In the future it would be useful to investigate cell growth and morphology using three-dimensional imaging methods.

A New Goniothalamin N-acylated Aza-derivative Strongly Downregulates Mediators Of Signaling Transduction Associated With Pancreatic Cancer Aggressiveness.

In this study, a novel concise series of molecules based on the structure of goniothalamin (1) was synthesized and evaluated against a highly metastatic human pancreatic cancer cell line (Panc-1). Among them, derivative 8 displayed a low IC50 value (2.7 μM) and its concentration for decreasing colony formation was 20-fold lower than goniothalamin (1). Both compounds reduced the levels of the receptor tyrosine kinase (AXL) and cyclin D1 which are known to be overexpressed in pancreatic cancer cells. Importantly, despite the fact that goniothalamin (1) and derivative 8 caused pancreatic cancer cell cycle arrest and cell death, only derivative 8 was able to downregulate pro-survival and proliferation pathways mediated by mitogen activated protein kinase ERK1/2. Another interesting finding was that Panc-1 cells treated with derivative 8 displayed a strong decrease in the transcription factor (c-Myc), hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) protein levels. Notably, the molecular effects caused by derivative 8 might not be related to ROS generation, since no significant production of ROS was observed in low concentrations of this compound (from 1.5 up to 3 μM). Therefore, the downregulation of important mediators of pancreatic cancer aggressiveness by derivative 8 reveals its great potential for the development of new chemotherapeutic agents for pancreatic cancer treatment.

A New Platinum Complex With Tryptophan: Synthesis, Structural Characterization, Dft Studies And Biological Assays In Vitro Over Human Tumorigenic Cells.

A new platinum(II) complex with the amino acid L-tryptophan (trp), named Pt-trp, was synthesized and characterized. Elemental, thermogravimetric and ESI-QTOF mass spectrometric analyses led to the composition [Pt(C11H11N2O2)2]⋅6H2O. Infrared spectroscopic data indicate the coordination of trp to Pt(II) through the oxygen of the carboxylate group and also through the nitrogen atom of the amino group. The (13)C CP/MAS NMR spectroscopic data confirm coordination through the oxygen atom of the carboxylate group, while the (15)N CP/MAS NMR data confirm coordination of the nitrogen of the NH2 group to the metal. Density functional theory (DFT) studies were applied to evaluate the cis and trans coordination modes of trp to platinum(II). The trans isomer was shown to be energetically more stable than the cis one. The Pt-trp complex was evaluated as a cytotoxic agent against SK-Mel 103 (human melanoma) and Panc-1 (human pancreatic carcinoma) cell lines. The complex was shown to be cytotoxic over the considered cells.

Impact Of Drug Formulation And Free Platinum/cisplatin Ratio On Hypersensitivity Reactions To Cisplatin: Formulation Matters.

Use of cisplatin can induce type I hypersensitivity reactions that may also be linked to the quality of the drug utilized. We observed cases of hypersensitivity that appeared to be associated with the brand of cisplatin used. The aim of this study was to compare two different brands of cisplatin in relation to type I hypersensitivity reactions. Brand A was used in a tertiary care teaching hospital until 2012, and use of brand B started from January 2013, when the first hypersensitivity cases were observed. Patients were categorized based on symptom. Cisplatin of both brands was analysed by high-performance liquid chromatography (HPLC) and high-resolution electrospray ionization mass spectrometry (ESI-(+)-MS) and characterized according to US Pharmacopeia. There were no cases of hypersensitivity associated with the use of cisplatin brand A, whereas four of 127 outpatients that used cisplatin brand B were affected. The two brands were in accordance with the US Pharmacopeia parameters, and there was no significant difference in the total platinum levels between the two brands when analysed by HPLC. However, high-resolution ESI-(+)-MS analyses show that brand B contains approximately 2.7 times more hydrolysed cisplatin than brand A. The increase in the hydrolysed form of cisplatin found in brand B may be the cause of the hypersensitivity reaction observed in a subset of patients. We present the first study of the quality of drugs by high-resolution ESI-(+)-MS. Drug regulatory agencies and manufacturers should consider including measurement of hydrolysed cisplatin as a quality criterion for cisplatin formulations.

Effect of temperature on the electro-oxidation of ethanol on platinum

We present in this work an experimental investigation of the effect of temperature (from 25 to 180 ºC) in the electro-oxidation of ethanol on platinum in two different phosphoric acid concentrations. We observed that the onset potential for ethanol electro-oxidation shifts to lower values and the reaction rates increase as temperature is increased for both electrolytes. The results were rationalized in terms of the effect of temperature on the adsorption of reaction intermediates, poisons, and anions. The formation of oxygenated species at high potentials, mainly in the more diluted electrolyte, also contributes to increase the electro-oxidation reaction rate.

Higher-derivative supersymmetric gauge theory

We study the one-loop low-energy effective action for the higher-derivative superfield gauge theory coupled to chiral matter.

Potent Cardioprotective Effect of the 4-Anilinoquinazoline Derivative PD153035: Involvement of Mitochondrial K(ATP) Channel Activation

Background: The aim of the present study was to evaluate the protective effects of the 4-anilinoquinazoline derivative PD153035 on cardiac ischemia/reperfusion and mitochondrial function. Methodology/Principal Findings: Perfused rat hearts and cardiac HL-1 cells were used to determine cardioprotective effects of PD153035. Isolated rat heart mitochondria were studied to uncover mechanisms of cardioprotection. Nanomolar doses of PD153035 strongly protect against heart and cardiomyocyte damage induced by ischemia/reperfusion and cyanide/aglycemia. PD153035 did not alter oxidative phosphorylation, nor directly prevent Ca(2+) induced mitochondrial membrane permeability transition. The protective effect of PD153035 on HL-1 cells was also independent of AKT phosphorylation state. Interestingly, PD153035 activated K(+) transport in isolated mitochondria, in a manner prevented by ATP and 5-hydroxydecanoate, inhibitors of mitochondrial ATP-sensitive K(+) channels (mitoK(ATP)). 5-Hydroxydecanoate also inhibited the cardioprotective effect of PD153035 in cardiac HL-1 cells, demonstrating that this protection is dependent on mitoK(ATP) activation. Conclusions/Significance: We conclude that PD153035 is a potent cardioprotective compound and acts in a mechanism involving mitoK(ATP) activation.

Temperature effects on the oscillatory electro-oxidation of methanol on platinum

We report in this paper the effect of temperature on the oscillatory electro-oxidation of methanol on polycrystalline platinum in aqueous sulfuric acid media. Potential oscillations were studied under galvanostatic control and at four temperatures ranging from 5 to 35 degrees C. For a given temperature, the departure from thermodynamic equilibrium does not affect the oscillation period and results in a slight increase of the oscillation amplitude. Apparent activation energies were also evaluated in voltammetric and chronoamperometric experiments and were compared to those obtained under oscillatory conditions. In any case, the apparent activation energies values fell into the region between 50 and 70 kJ mol(-1). Specifically under oscillatory conditions an apparent activation energy of 60 +/- 3 kJ mol(-1) and a temperature coefficient q(10) of about 2.3 were observed. The present findings extend our recently published report (J. Phys. Chem. A, 2008, 112, 4617) on the temperature effect on the oscillatory electro-oxidation of formic acid. We found that, despite the fact that both studies were carried out under similar conditions, unlike the case of formic acid, only conventional, Arrhenius, dynamics was observed for methanol.

The role of the steps in the cleavage of the C-C bond during ethanol oxidation on platinum electrodes

Ethanol oxidation has been studied on stepped platinum single crystal electrodes in acid media using electrochemical and Fourier transform infrared (FTIR) techniques. The electrodes used belong to two different series of stepped surfaces: those having (111) terraces with (100) monoatomic steps and those with (111) terraces with (110) monoatomic steps. The behaviors of the two series of stepped surfaces for the oxidation of ethanol are very different. On the one hand, the presence of (100) steps on the (111) terraces provides no significant enhancement of the activity of the surfaces. On the other hand, (110) steps have a double effect on the ethanol oxidation reaction. At potentials below 0.7 V, the step catalyzes the C-C bond cleavage and also the oxidation of the adsorbed CO species formed. At higher potentials, the step is not only able to break the C-C bond, but also to catalyze the oxidation of ethanol to acetic acid and acetaldehyde. The highest catalytic activity from voltammetry for ethanol oxidation was obtained with the Pt(554) electrode.