Novel separation method for highly sensitive speciation of cancerostatic platinum compounds by HPLC–ICP–MS

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 g L^–1, respectively, were calculated at m/z 194, using aqueous standard solutions. (3 L 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.     

Modeling rate-controlling solvent effects. The pericyclic meisenheimer rearrangement of N-propargylmorpholine N-oxide

The activation parameters of the pericyclic Meisenheimer rearrangement and a competitive rearrangement of N-propargylmorpholine N-oxide were determined by experimental and computational methods. A number of aprotic and protic solvents of different polarities and hydrogen bond-forming abilities and the roles of electron-pair acceptor additives were investigated. The reaction kinetics were followed by means of NMR. In protic solvents, isotope-labeling experiments revealed a novel inverse secondary kinetic isotope effect (k(H)/k(D) about 0.8) for the rate-determining cyclization step, probably occurring because of a C(sp) --> C(sp(2)) change in hybridization at the reaction center. In molecular computations at the B3LYP/6-31++G(d,p) level of theory, implicit, explicit, and joint explicit-implicit solvent models were used. The explicit-implicit model and molecular dynamic simulations gave the most accurate results. The components of the rate-controlling solvent effect are discussed, and general equations are proposed for accurate prediction of the solvent-dependent activation parameters.     

Coordination modes between copper(II) and N-acetylneuraminic (sialic) acid from a 2D-simulation analysis of EPR spectra. Implications for copper mediation of sialoglycoconjugate chemistry relevant to human biology

The equilibrium distribution of species formed between Cu(II) and N-acetylneuraminic (sialic) acid (I, LH) at 298 K has been determined using a two-dimensional (2D) simulation analysis of electron paramagnetic resonance (EPR) spectra. In acidic solutions (pH values < 4), the major species present are Cu(2+), [CuL]+ [logbeta = 1.64(4)], and [CuL2] [logbeta = 2.77(5)]. At intermediate pH values (4.0 < pH < 7.5), [CuL2H-1]- [logbeta = -2.72(7)] and two isomers of [CuLH-1] [logbeta (overall) = -3.37(2)] are present. At alkaline pH values (7.5 < pH < 11), the major species present is [CuL2H-2]2-, modeled as three isomers with unique giso and Aiso values [logbeta (overall) = -8.68(3)]. Two further species ([CuLH-3]2- and [CuL2H-3]3-) appear at pH values > 11. It is proposed that [CuL]+ most likely features I coordinated via the deprotonated carboxylic acid group (O1) and the endocyclic oxygen atom (OR) forming a five-membered chelate ring. Select Cu(II)-I species of the form [CuLH-1] may feature I acting as a dianionic tridentate chelate, via oxygen atoms derived from O1, OR, and one deprotonated hydroxy group (O7 or O8) from the glycerol tail. Alternatively, I may coordinate Cu(II) in a bidentate fashion as the tert-2-hydroxycarboxylato (O1,O2) dianion. Spectra predicted for Cu(II)-I complexes in which I is coordinated in either a O1,OR {I1-} or O1,O2 {I2-} bidentate fashion {e.g., [CuL]+ (O1,O R), [CuL2] (bis-O1,O R), [CuLH-1] (isomer: O1, O2), [CuL2H-1]- (O1, O R; O1, O2), and [CuL2H-2]2- (isomer: bis-O1, O2)} have "irregular" EPR spectra that are ascribed to the existence of Cu(II)-I(monomer) <==> Cu(II)-I(polymer) equilibria. The formation of polymeric Cu(II)-I species will be favored in these complexes because the glycerol-derived hydroxyl groups at the complex periphery (O, 7O, 8O9) are available for further Cu(II) binding. The presence of polymeric Cu(II)-I species is supported by EPR spectral data from solutions of Cu(II) and the homopolymer of I, colominic acid (Ipoly). Conversely, spectra predicted for Cu(II)-I complexes where I is coordinated in a {I2-} tridentate {e.g., [CuLH-1] (isomer: O1, O R, O7, or O8) and [CuL2H-2]2- (isomer: bis-O1,O R,O7, or O8)} or tetradentate fashion {I3-} {e.g., [CuLH-3]2- (O1, O R, O, 8O9)} are typical for mononuclear tetragonally elongated Cu(II) octahedra. In this latter series of complexes, the tendency toward the formation of polymeric Cu(II)-I analogues is small because the polydentate I effectively wraps up the mononuclear Cu(II) center. This work shows that Cu(II) could potentially mediate the chemistry of sialoglycoconjugate-containing proteins in human biology, such as the sialylated amyloid precursor protein of relevance to Alzheimer's disease.     

Studies on stereoselective approaches to β-carboline derivatives

Transformation of β-carboline derivatives into optically active entities were studied and the de and ee values of the resulted compounds were detected. Dedicated to Professor Károly Lempert on his 80th birthday.     

Electrospray mass spectrometry of hydrophobic compounds using dimethyl sulfoxide and dimethylformamide as solvents.

The use of dimethyl sulfoxide (DMSO) and dimethylformamide (DMF) as solvents in electrospray ionization (ESI) is suggested for the analysis of hydrophobic compounds. Its use was shown to overcome solubility problems and resulted in good quality electrospray spectra of protected hydrophobic peptides, sugars and other hydrophobic compounds. Intense protonated and/or sodiated molecules were formed in positive ion mode while negative ion mode resulted in [M + 95](-) ions from DMSO and [M + Cl](-) ions from DMF in cases where no significant molecular ion related peaks could be observed applying commonly used protic solvents such as methanol or acetonitrile. Deuterium labeling (d6-DMSO), high resolution experiments and tandem mass spectrometric measurements showed that the methanesulfonic acid (MSA), present in DMSO as a common impurity, is responsible for the formation of protonated molecules in positive ion mode and for methane sulfonate anion adducts [M + 95](-) in negative ion mode.     

On the symmetry-breaking bifurcation of chaotic attractors

A new type of crisis is shown to exist in a broad class of systems (including the Lorenz model) which leads to an anomalous band splitting or to a symmetry-breaking bifurcation of the strange attractor, depending on the actual values of the control parameters. A piecewise linear model is used to understand the mechanism of this crisis and to obtain exact results.     

An Efficient Method for using Molecular Symmetry. In Advance Selection of Zero Integrals

The molecular symmetry has previously been used in an effective way for the reduction of the number of two-electron integrals to be calculated. Here the method is further developed in such a way that the zero integrals due to the molecular symmetry can be easily selected in advance. It is pointed out, that this method, without using indices for the integrals does not need extra computational effort. The gain in computer time has been shown in the case of normal saturated hydrocarbons.     

Isolation of Some Antimicrobial Compounds of Red Wine by OPLC Flowing Eluent Wall Technique

The first results of the combination of BioArena and OPLC with flowing eluent wall technique (FEW) show an especially attractive solution of the detection of antimicrobial activity and compound isolation based on peak collection. Because of the different separation mechanisms applied for on-line FEW–OPLC isolation of red wine constituents and for further off-line OPLC investigation of fractions, the combined system yields high selectivity.     

Electrons from target and projectile ionization in simple collision systems

Summary Absolute double differential cross-sections for target ionization and projectile electron loss were determined in collisions of H⁺, H₂ ⁺,³He⁺ and³He⁺⁺ ions (0.4 to 2.0 Me V/u) with He and Ar gas targets at electron emission angles from 0° up to 60°. The experimental results are qualitatively well described by plane-wave Born approximations including screening of the projectile in target ionization and of the target atom in the case of electron loss.

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Riassunto Sono state determinate le sezioni d’urto doppie differenziali assolute per la ionizzazione del bersaglio e la perdita dell’elettrone proiettile in collisioni di ioni H⁺, H ₂ ⁺ ,³He⁺ e³He⁺⁺ (da 0.4 a 2.0 Me V/u) con bersagli di gas He e Ar ad angoli di emissione degli elettroni da 0° a 60°. I risultati sperimentali sono qualitativamente ben descritti dalle approssimazioni di Born per onde piane che comprendono la schermatura del proiettile nella ionizzazione del bersaglio e dell’atomo bersaglio nel caso di perdita dell’elettrone.

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Резюме Определяются абсолютные дважды дифференшиальные поперечные сечения для ионизации мишени и потери электровов налетающими частишами при соударениях ионов H⁺, H ₂ ⁺ ,³He⁺ и³He⁺⁺ (от 0.4 до 2.0 Me V/u) в случае газовых Не и Ar мишеней при углах эмиссии электронов от 0° до 60°. Экспериментальные результаты качественно хорощо описываются с помощью плоско-волнового борновского приближения, включая экранирование налетающей частицы при ионизации мишени в случае потери электрона.