RESUMEN
A series of platinum(II) amidine complexes were previously prepared with the aim of obtaining a new class of platinum-based antitumour drugs. This series includes compounds of the type cis--[PtCl2{Z-HN=C(NHMe)Me}2] and trans-[PtCl2{Z-HN=C(NHMe)Me}2] (1, 2), cis-[PtCl2{E-HN=C(NMe2)Me}2] and trans-[PtCl2{E-HN=C(NMe2)Me}2] (3, 4), cis-[PtCl2{Z-HN=C(NHMe)Ph}2] and trans-[PtCl2{Z-HN=C(NHMe)Ph}2] (5, 6), and cis-[PtCl2{HN=C(NMe2)Ph}2] and trans-[PtCl2{HN=C(NMe2)Ph}2] (7, 8). The reactions with dimethyl sulfoxide were studied for complexes 5-8; the formation of cationic species containing coordinated dimethyl sulfoxide was demonstrated by NMR experiments and electrospray ionization mass spectrometry. In this work, the amidine platinum(II) complexes were tested for their in vitro cytotoxicity on a panel of various human cancer cell lines. The results indicate that the benzamidine complex 8 was the most effective derivative also circumventing acquired cisplatin resistance as demonstrated by chemosensitivity tests performed on cisplatin-sensitive and cisplatin-resistant cell lines. The studies concerning the cellular DNA damage on both parental chemosensitive and resistant sublines suggest for the new trans-amidine complex a different mechanism of action compared with that exhibited by cisplatin.
Asunto(s)
Furanos/química , Furanos/toxicidad , Compuestos de Platino/química , Compuestos de Platino/toxicidad , Amidinas/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Reactivos de Enlaces Cruzados/química , Reactivos de Enlaces Cruzados/farmacología , ADN/química , ADN/metabolismo , Humanos , Isomerismo , Espectroscopía de Resonancia Magnética , Estructura Molecular , Compuestos de Platino/aislamiento & purificación , Soluciones , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
An environmentally friendly method using the metal ion-reducing bacterium Shewanella algae was proposed to deposit platinum nanoparticles. Resting cells of S. algae were able to reduce aqueous PtCl(6)(2-) ions into elemental platinum at room temperature and neutral pH within 60min when lactate was provided as the electron donor. Biogenic platinum nanoparticles of about 5nm were located in the periplasm--a preferable, cell surface location for easy recovery of biogenic nanoparticles.
Asunto(s)
Galvanoplastia/métodos , Compuestos de Platino/metabolismo , Shewanella/metabolismo , Biodegradación Ambiental , Nanopartículas del Metal/química , Oxidación-Reducción , Periplasma/química , Compuestos de Platino/química , Compuestos de Platino/aislamiento & purificación , Shewanella/ultraestructura , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/aislamiento & purificación , Contaminantes Químicos del Agua/metabolismoRESUMEN
Due to advances in nanotechnology, the approach to catalytic design is transitioning from trial-and-error to planned design and control. Expected advances should enable the design and construction of catalysts to increase reaction speed, yield, and catalyst durability while also reducing active species loading levels. Nanofabrication techniques enabling precise control over the shape, size, and position of nanoscale platinum-group metal (PGM) particles in automotive catalysts should result in reduced PGM loading levels. These reductions would decrease energy consumption, improve environmental quality, and contribute to sustainable resource usage. We estimate the amount of PGM required to meet U.S. vehicle emissions standards through 2030 based on current catalysttechnology. We then estimate the range of PGM that could be saved from potential nanotechnology advances. Finally, we employ economic input-output and process-based life cycle assessment models to estimate the direct and life cycle benefits from reducing PGM mining and refining.
Asunto(s)
Contaminación del Aire/prevención & control , Nanotecnología/métodos , Compuestos de Platino/aislamiento & purificación , Emisiones de Vehículos , Contaminación del Aire/economía , Catálisis , Costos y Análisis de Costo , Diseño de Equipo , Nanotecnología/economíaRESUMEN
Microemulsion electrokinetic chromatography (MEEKC) was applied for the separation and lipophilicity estimation of oxaliplatin and eight novel anticancer oxaliplatin derivatives. Solubility and permeability have to be balanced in modern drug development, and the octanol-water partition coefficient (log P) still represents one of the most useful quantifiable parameters providing a reasonable estimation of a drug's lipophilicity. Therefore, the capacity factors from MEEKC were correlated to log P values derived by the traditional shake flask method. The MEEKC method was accomplished using a microemulsion of heptane/sodium dodecyl sulfate (SDS)/butanol in phosphate buffer at pH 7.4 and 37 degrees C with all analytes being in a neutral state during the run. This experimental setup allowed a baseline separation of all platinum complexes within 11 min. Remarkably, beside the very good resolution and precision of the measurements, separation of diastereomers of the complexes and quantification of the diastereomeric ratios could be achieved. Correlating the capacity factors with the corresponding log P values resulted in a linear dependency with a correlation factor of r = 0.9935. Consequently, the applied MEEKC method was found to be a highly valuable technique not only for the separation of platinum complexes but as well for the estimation of the octanol-water partition coefficient with many advantages in comparison to other methods.
Asunto(s)
Antineoplásicos/aislamiento & purificación , Cromatografía Capilar Electrocinética Micelar/métodos , Compuestos de Platino/aislamiento & purificación , Electroforesis Capilar/métodos , Emulsiones , Reproducibilidad de los ResultadosRESUMEN
A high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) method is presented for analysis of cisplatin, monoaquacisplatin, diaquacisplatin, carboplatin, and oxaliplatin in biological and environmental samples. Chromatographic separation was achieved on pentafluorophenylpropyl-functionalized silica gel. For cisplatin, carboplatin, and oxaliplatin limits of detection of 0.09, 0.10, and 0.15 microg L(-1), respectively, were calculated at m/z 194, using aqueous standard solutions. (3 microL injection volume). The method was utilized for model experiments studying the stability of carboplatin and oxaliplatin at different chloride concentrations simulating wastewater and surface water conditions. It was found that a high fraction of carboplatin is stable in ultrapure water and in solutions containing 1.5 mol L(-1) Cl-, whereas oxaliplatin degradation was increased by increasing the chloride concentration. In order to support the assessment of oxaliplatin eco-toxicology, the method was tested for speciation of patient urine. The urine sample contained more than 17 different reaction products, which demonstrates the extensive biotransformation of the compound. In a second step of the study the method was successfully evaluated for monitoring cancerostatic platinum compounds in hospital waste water.
Asunto(s)
Antineoplásicos/aislamiento & purificación , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas/métodos , Compuestos de Platino/aislamiento & purificación , Antineoplásicos/clasificación , Antineoplásicos/orina , Humanos , Compuestos de Platino/clasificación , Compuestos de Platino/orina , Sensibilidad y EspecificidadRESUMEN
Terminal mono-oxo complexes of the late transition metal elements have long been considered too unstable to synthesize because of repulsion between the oxygen electrons and the mostly filled metal d orbitals. A platinum(IV)-oxo compound flanked by two polytungstate ligands, K7Na9[O=Pt(H2O)L2], L = [PW9O34(9-)], has now been prepared and isolated at room temperature as air-stable brown crystals. X-ray and neutron diffraction at 30 kelvin revealed a very short [1.720(18) angstrom] Pt-O bond and no evidence of a hydrogen atom at the terminal oxygen, ruling out a better precedented Pt-OH complex. Density functional theory and spectroscopic data account for the stability of the Pt(IV)-oxo unit by electron withdrawal into delocalized orbitals of the polytungstates.