Validation of a robust and rapid liquid chromatography tandem mass spectrometric method for the quantitative analysis of navitoclax

The Bcl-2 family small molecule inhibitor navitoclax is being clinically evaluated to treat multiple cancers including lymphoid malignancies and small cell lung cancer. A sensitive and reliable method was developed to quantitate navitoclax in human plasma using liquid chromatography with tandem mass spectrometry with which to perform detailed pharmacokinetic studies. Sample preparation involved protein precipitation using acetonitrile. Separation of navitoclax and the internal standard, navitoclax-d8, was achieved with a Waters Acquity UPLC BEH C₁₈ column using isocratic flow over a 3 min total analytical run time. A SCIEX 4500 triple quadrupole mass spectrometer operated in positive electrospray ionization mode was used for the detection of navitoclax. The assay range was 5–5,000 ng/ml and proved to be accurate (89.5–104.9%) and precise (CV ≤ 11%). Long-term frozen plasma stability for navitoclax at −70°C was at least 43 months. The method was applied for the measurement of total plasma concentration of navitoclax in a patient receiving a 250 mg daily oral dose.     

Solvent‐Dependent Structure of the I3− Ion Derived from Photoelectron Spectroscopy and Ab Initio Molecular Dynamics Simulations

Ab initio molecular dynamics (MD) simulations of the solvation of LiI₃ in four different solvents (water, methanol, ethanol, and acetonitrile) are employed to investigate the molecular and electronic structure of the I₃^? ion in relation to X‐ray photoelectron spectroscopy (XPS). Simulations show that hydrogen‐bond rearrangement in the solvation shell is coupled to intramolecular bond‐length asymmetry in the I₃^? ion. By a combination of charge analysis and I 4 d core‐level XPS measurements, the mechanism of the solvent‐induced distortions has been studied, and it has been concluded that charge localization mediates intermolecular interactions and intramolecular distortion. The approach involving a synergistic combination of theory and experiment probes the solvent‐dependent structure of the I₃^? ion, and the geometric structure has been correlated with the electronic structure.     

Impact of Initial Wettability and Injection Brine Chemistry on Mechanical Behaviour of Kansas Chalk

Transport in Porous Media - The injection of seawater-like brines alters stiffness, strength and time-dependent deformation rates for water-saturated chalks. This study deals with the mechanical...     

Facile synthesis of dopa‐functional polycarbonates via thiol‐Ene‐coupling chemistry towards self‐healing gels

Since extraction of the naturally occurring mussel‐foot proteins is expensive and time‐consuming, routes towards synthetic analogues are continuously being explored. Often, these methods involve several protection and deprotection steps, making the synthesis of synthetic analogues time‐consuming and expensive as well. Herein, we show that UV‐initiated thiol‐ene coupling between a thiol‐functional dopamine derivative and an allyl‐functional aliphatic polycarbonate can be used as a fast and facile route to dopa‐functional materials. Different thiol‐to‐allyl ratios and irradiation protocols were used and it was found that nearly 50% of the allyl groups could be functionalized with dopa within short reaction times, without the need of protecting the catechol. It is also demonstrated herein that the dopa‐functional polymers can be used to form self‐healing gels through complexation with Fe³⁺ ions at increased pH. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 2370–2378     

A posteriori error analysis of round-off errors in the numerical solution of ordinary differential equations

We prove sharp, computable error estimates for the propagation of errors in the numerical solution of ordinary differential equations. The new estimates extend previous estimates of the influence of data errors and discretization errors with a new term accounting for the propagation of numerical round-off errors, showing that the accumulated round-off error is inversely proportional to the square root of the step size. As a consequence, the numeric precision eventually sets the limit for the pointwise computability of accurate solutions of any ODE. The theoretical results are supported by numerically computed solutions and error estimates for the Lorenz system and the van der Pol oscillator.     

理论研究晶体场效应和电荷转移效应对Co2+的2p电子X射线L2,3吸收边光谱的影响

运用多重态计算方法研究了在正八面体对称性的晶体场中Co²⁺离子的2p电子X射线L_2,3吸收边光谱, 研究了Co²⁺离子和周围的配位离子之间的正八面体(O_h)晶体场效应和相应的电荷转移效应对于吸收光谱的影响. 系统讨论了在多重态计算中起作用的所有物理参数对CoO和CoCl₂的X射线吸收光谱特性的特定影响及其物理机制. 将计算得出的光谱数据和同样具有O_h对称性结构Co²⁺离子的CoO和CoCl₂实验光谱数据进行了对比, 在实验光谱数据中发现的特征被确定为来自不同自旋态, 并且光谱强度的变化与晶体场的强度相关, 揭示了其中包含的电荷转移效应. 本文为低对称性复杂系统的多重态计算提供了一个基础的参考标准, 可以适用于含有钴元素或其它过渡金属的复杂体系的X射线吸收光谱的理论计算.