Development of an HPLC Method for Determination of Related Impurities in Prilocaine Substance

Development of a reversed phase high performance liquid chromatographic method for determination of six related impurities in prilocaine substance is reported. The test of related impurities in European Pharmacopoeia (Ph. Eur.) cannot meet the demands with the chromatographic parameters given, therefore different types of chromatographic systems and eight columns have been evaluated in the present study. A new method with a Hypercarb column was developed and validated. This method fulfils the demands in the Ph. Eur., and the validation shows that the method is selective, reproducible, linear, accurate and robust with sufficient limits of detection (0.001–0.004% of 2.5?mg prilocaine mL^?1) and quantification (0.002–0.009% of 2.5?mg prilocaine mL^?1).     

Malatoplatinum(II) complexes – carboplatin analogs

A series of new neutral dicarboxylatoplatinum(II) complexes, containing D(+), L(−) or DL-malate dianion and ethylenediamine, 1-ethylimidazole or 1-propylimidazole as amine ligands, have been synthesized and characterized by elemental analysis, t.l.c., conductance, i.r., n.m.r., mass spectra (m/z) and electronic spectra. The new cytotoxic malatoplatinum(II) complexes are very soluble in water and resist hydrolysis. Their reactivity against glutathione is comparable with the reactivity of carboplatin, which suggests that these new complexes may be promising candidates in the search for low toxicity platinum cytostatics. This revised version was published online in June 2006 with corrections to the Cover Date.     

Implications of active site constraints on varied DNA polymerase selectivity

DNA polymerase selectivity often varies significantly depending on the DNA polymerase. The origin of this varying error propensity is elusive. It is assumed that DNA polymerases form nucleotide binding pockets that differ in properties such as shape and tightness. We tested this prediction and studied HIV-1 RT by employment of size-augmented nucleotides and site-directed mutagenesis of the enzyme. New valuable insights into the mechanism of DNA polymerase fidelity were obtained. The presented study provides experimental evidence that variations of steric constraints within the nucleotide binding pocket of at least two DNA polymerases cause variations in nucleotide incorporation selectivity. Thus, our results support the concept of active site tightness as a causative in differential fidelity among DNA polymerases.     

Kinetic study of free‐radical polymerization photoinitiated by cyanine‐borate salts. II.

A series of cyanine butyltriphenylborate salts were prepared and tested as initiators of free‐radical polymerization photoinitiated via a photoinduced electron‐transfer process. For the majority of the tested series, the highest rate of photoinitiated free‐radical polymerization was observed when sec‐butyl radicals were formed. Essentially, there was no influence of the quantum yield of the free‐radical formation on the rate of the free‐radical polymerization initiated by the cyanine‐borate salts. The experimental data revealed that the relationship between the rate of polymerization and the free energy change for the electron transfer displayed typical Marcus region kinetic behavior. The photoreduction of the cyanine butyltriphenylborate salts produced colorless products. The efficiency of the bleached‐dye formation had no effect on the overall efficiency of photoinitiated polymerization. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 2365–2374, 2000     

Gas-Phase Lithium Cation Basicity: Revisiting the High Basicity Range by Experiment and Theory

According to high level calculations, the upper part of the previously published FT-ICR lithium cation basicity (LiCB at 373 K) scale appeared to be biased by a systematic downward shift. The purpose of this work was to determine the source of this systematic difference. New experimental LiCB values at 373 K have been measured for 31 ligands by proton-transfer equilibrium techniques, ranging from tetrahydrofuran (137.2 kJ mol^?1) to 1,2-dimethoxyethane (202.7 kJ mol^?1). The relative basicities (ΔLiCB) were included in a single self-consistent ladder anchored to the absolute LiCB value of pyridine (146.7 kJ mol^?1). This new LiCB scale exhibits a good agreement with theoretical values obtained at G2(MP2) level. By means of kinetic modeling, it was also shown that equilibrium measurements can be performed in spite of the formation of Li⁺ bound dimers. The key feature for achieving accurate equilibrium measurements is the ion trapping time. The potential causes of discrepancies between the new data and previous experimental measurements were analyzed. It was concluded that the disagreement essentially finds its origin in the estimation of temperature and the calibration of Cook’s kinetic method. Graphical Abstract

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Trends in single-cell analysis by use of ICP-MS

The analysis of single cells is a growing research field in many disciplines such as toxicology, medical diagnosis, drug and cancer research or metallomics, and different methods based on microscopic, mass spectrometric, and spectroscopic techniques are under investigation. This review focuses on the most recent trends in which inductively coupled plasma mass spectrometry (ICP-MS) and ICP optical emission spectrometry (ICP-OES) are applied for single-cell analysis using metal atoms being intrinsically present in cells, taken up by cells (e.g., nanoparticles), or which are artificially bound to a cell. For the latter, especially element tagged antibodies are of high interest and are discussed in the review. The application of different sample introduction systems for liquid analysis (pneumatic nebulization, droplet generation) and elemental imaging by laser ablation ICP-MS (LA-ICP-MS) of single cells are highlighted. Because of the high complexity of biological systems and for a better understanding of processes and dynamics of biologically or medically relevant cells, the authors discuss the idea of “multimodal spectroscopies.”     

Four‐ and five‐coordinate copper(II) complexes with N‐(4,4‐diphenyl‐5‐oxo‐4,5‐dihydro‐1H‐imidazol‐2‐yl)glycine

The two title mononuclear compounds are four‐coordinate bis[N‐(5‐oxo‐4,4‐diphenyl‐4,5‐dihydro‐1H‐imidazolidin‐2‐ylidene)glycinato]copper(II) dimethylformamide disolvate, [Cu(C₁₇H₁₄N₃O₃)₂]·2C₃H₇NO, (I), and five‐coordinate aquabis[N‐(5‐oxo‐4,4‐diphenyl‐4,5‐dihydro‐1H‐imidazolidin‐2‐ylidene)glycinato]copper(II) dimethylformamide disolvate, [Cu(C₁₇H₁₄N₃O₃)₂(H₂O)]·2C₃H₇NO, (II). In (I), the Cu^II ion lies on an inversion centre with one‐half of the complex molecule in the asymmetric unit, while in (II) there are two independent ligand molecules in the asymmetric unit, with the Cu^II ion and coordinated water molecule located on a general position. In both crystal structures, the complex molecules assemble in ribbons via N—H...O hydrogen‐bond networks.     

Effective Control of the Electron-donating Ability of Phosphines by using Phosphazenyl and Phosphoniumylidyl Substituents

Phosphoniumylidyl and phosphazenyl groups are effective substituents to increase the electron-donating ability of tertiary phosphines. However, the influence of structural variations among those substituents on the electronic properties of the phosphines is little explored. Herein, we show that protonation of the ylidic carbon atom of phosphoniumylidyl phosphines increases the Tolman electronic parameter (TEP) by ΔTEP = 16.0–18.8 cm^–1. Furthermore, phosphazenyl phosphines were synthesized with isopropyl groups (NP{iPr}₃) and tetramethylguanidino groups (NP{tmg}₃) at the phosphonium center. Determination of their TEP values reveals a remarkable low substituent parameter of χ = –18.5 cm^–1 for the NP(tmg)₃ group. In addition, we prepared the corresponding gold(I) complexes and determined their solid-state structures using single-crystal X-ray diffraction studies to analyze the steric profile of the new phosphine ligands.