An Alternative Synthesis of 2-Chloro-5-Hydroxypyridine: A Key Component of the Non-Opioid Analgesic Agent ABT-594

The synthesis of the biologically useful synthon 2-chloro-5-hydroxypyridine from 3-iodo-6-chloropyridine is described.     

Imaging and sizing of diamond nanoparticles

Typical disturbances of biological environment such as background scatter and refractive index variations have little effect on the size-dependent scattering property of highly refractive nanocrystals, which are potentially attractive optical labels. We report on what is to our knowledge the first investigation of these scattering optical labels, and their sizing, in particular, by imaging at subvideo frame rates and analyzing samples of diamond nanocrystals deposited on a glass substrate in air and in a matrix of weakly scattering polymer. The brightness of a diffraction-limited spot appears to serve as a reliable measure of the particle size in the Rayleigh scattering limit.     

Metabolomics profiling of extracellular metabolites in recombinant Chinese Hamster Ovary fed‐batch culture

A metabolomics‐based approach was used to time profile extracellular metabolites in duplicate fed‐batch bioreactor cultures of recombinant Chinese Hamster Ovary (CHO) cells producing monoclonal IgG antibody. Culture medium was collected and analysed using a high‐performance liquid chromatography (HPLC) system in tandem with an LTQ‐Orbitrap mass spectrometer. An in‐house software was developed to pre‐process the LC/MS data in terms of filtering and peak detection. This was followed by principal component analysis (PCA) to assess variance amongst the samples, and hierarchical clustering to categorize mass peaks by their time profiles. Finally, LC/MS² experiments using the LTQ‐Orbitrap (where standard was available) and SYNAPT? HDMS (where standard was unavailable) were performed to confirm the identities of the metabolites. Two groups of identified metabolites were of particular interest; the first consisted of metabolites that began to accumulate when the culture entered stationary phase. The majority of them were amino acid derivatives and they were likely to be derived from the amino acids in the feed media. Examples included acetylphenylalanine and dimethylarginine which are known to be detrimental to cell growth. The second group of metabolites showed a downward trend as the culture progressed. Two of them were medium components – tryptophan and choline, and these became depleted midway into the culture despite the addition of feed media. The findings demonstrated the potential of utilizing metabolomics to guide medium design for fed‐batch culture to potentially improve cell growth and product titer. Copyright © 2009 John Wiley & Sons, Ltd.     

Reinterpretation of curved Hammett plots in reaction of nucleophiles with aryl benzoates: change in rate-determining step or mechanism versus ground-state stabilization

A kinetic study is reported for the reaction of the anionic nucleophiles OH-, CN-, and N 3 - with aryl benzoates containing substituents on the benzoyl as well as the aryloxy moiety, in 80 mol % H2O - 20 mol % dimethyl sulfoxide at 25.0 degrees C. Hammett log k vs sigma plots for these systems are consistently nonlinear. However, a possible traditional explanation in terms of a mechanism involving a tetrahedral intermediate with curvature resulting from a change in rate-determining step is considered but rejected. The proposed explanation involves ground-state stabilization through resonance interaction between the benzoyl substituent and the electrophilic carbonyl center in the two-stage mechanism. Accordingly, the data are nicely accommodated on the basis of the Yukawa-Tsuno equation, which gives linear plots for all three nuceophiles. Literature reports of the mechanism of acyl transfer processes are reconsidered in this light.     

Thermodynamic systems for solids and liquids

The basic mathematical consequences which follow from the laws of thermodynamics are explored in a systematic new treatment for establishing fluid thermodynamic systems for a number of materials under conditions where they behave as fluids. For metals and many other solids, but less so for liquids, the specific heat at constant volume c_ν is sensibly constant at all temperatures above room temperature. The partial differential equation of thermodynamics which expresses the constancy of c_ν is easily solved, the solution involving two arbitrary functions of the specific volume. Various approaches are presented to illustrate how one may choose these functions to accord with experimental observations over large thermodynamic ranges, and so produce practical thermodynamic systems. Two complementary thermodynamic systems are presented, which embody significant experimental results; the first is based on linear shock velocity/particle velocity (U, u) relations; the second on the limiting value of the specific heat ratio $\text{c}{}_{\mathrm{p}}\text{c}{}_{\mathrm{v}}$ at high temperatures. They are complementary in the sense that the first has analytically complicated non-Hugoniot properties which differ insignificantly from the comparatively simple non-Hugoniot properties of the second; whilst the second has analytically complicated Hugoniot properties which differ insignificantly from the simple Hugoniot properties of the first. Together, then, the two systems may be combined to give comprehensive practical simplicity. The main interest in these thermodynamic systems lies in the study of the behaviour of liquids, metals and other solids in shock transitions and under extreme conditions such as occur in high velocity impact or in explosion phenomena; but they are also of importance in stress-wave analysis, where complete thermodynamic systems are required in order to derive stress-strain relationships which do not neglect the effects of temperature changes.