The calculation of physicochemical descriptors and their application in predicting properties of drugs and other compounds.

The work presented may be divided into two main sections: The first section focuses on the important aspect of compound descriptor determination. The method by which descriptors are obtained indirectly through compound solubility in organic solvents and direct water-solvent partition measurements is illustrated by example for drug compounds. This approach is extended through the derivation of gas-water and water-solvent partition equations for the n-alcohols which in the future will be available for use in descriptor determination. Importantly, the equation coefficients are also interpreted to deduce various physicochemical properties of the homologous series of alcohols. An alternative method to assign descriptors is probed through reversed-phase HPLC. Measurements are recorded for a series of solutes on several bonded phases and multivariate analysis is used to investigate the interrelationship between columns in an effort to isolate the most suitable phases. The second section is concerned with application of the Abraham General Solvation Equation to examine processes of special interest in drug design; aqueous solubility and intestinal absorption. An algorithm to predict water solubility is obtained containing an additional cross-term which is found to compensate at least partly for a melting point correction term. The amended equation is shown to be comparable in accuracy to commercially available packages for a test set of 268 structurally diverse compounds. Of further importance in drug delivery is the process of intestinal absorption. An extensive literature search provides evaluated absorption data for a large set of drug compounds and forms a strong basis for subsequent QSAR analysis. Intestinal absorption is found to be comparable in humans and rat, and predominantly dependent on the hydrogen-bonding capability of the drug. The mechanism of absorption is considered through transformation of the percent absorption data to an overall rate constant

PIV measurements in an aerated tank stirred by a down- and up-pumping axial flow impeller

Liquid phase hydrodynamics in an aerated tank stirred by a down- and an up-pumping pitched blade turbine have been investigated using Particle Image Velocimetry. The effect of agitator configuration and the gas phase on the mean velocity fields and turbulent quantities in the vessel have been investigated. The global mean gas holdup has also been evaluated for the two pumping conditions. For the gas flow rate used, the presence of gas only slightly alters the liquid flow patterns produced by both the down- and up-pumping configurations and causes a general decrease in the mean liquid velocities. The turbulent kinetic energy in the impeller discharge region was not affected by the presence of gas, but in the bulk of the tank, aeration caused a decrease in this value. Global gas holdup was found to be ~36% greater for the up-pumping impeller and a large amount of gas was found to be entrained by the primary circulation loop

Flow generated by radial flow impellers: PIV measurements and CFD simulations

Particle image velocimetry (PIV) and computational fluid dynamics (CFD) have been used to investigate the single phase and gas-liquid flow generated by a Scaba SRGT turbine. The key details of the trailing vortices, the turbulent flow around the impeller blades and the accumulation of gas have been studied by using PIV measurements and CFD simulations. Both the experimental and numerical results show that the flow and the trailing vortices are not altered significantly upon gassing. The simulated results are generally in good agreement with the experimental findings. The CFD simulations also show that only small low-pressure regions exist behind the blades of the Scaba turbine compared with the very large lowpressure zones formed by the Rushton turbine. These results enable better understanding of the improved performance of the Scaba turbine for gas-liquid dispersions compared with the Rushton turbine

The membrane-associated form of as1- casein interacts with cholesterol-rich detergent-resistant microdomains

Caseins, the main milk proteins, interact with colloidal calcium phosphate to form the casein micelle. The mesostructure of this supramolecular assembly markedly influences its nutritional and technological functionalities. However, its detailed molecular organization and the cellular mechanisms involved in its biogenesis have been only partially established. There is a growing body of evidence to support the concept that as1-casein takes center stage in casein micelle building and transport in the secretory pathway of mammary epithelial cells. Here we have investigated the membrane-associated form of as1-casein in rat mammary epithelial cells. Using metabolic labelling we show that as1-casein becomes associated with membranes at the level of the endoplasmic reticulum, with no subsequent increase at the level of the Golgi apparatus. From morphological and biochemical data, it appears that caseins are in a tight relationship with membranes throughout the secretory pathway. On the other hand, we have observed that the membrane-associated form of as1-casein co-purified with detergent-resistant membranes. It was poorly solubilised by Tween 20, partially insoluble in Lubrol WX, and substantially insoluble in Triton X-100. Finally, we found that cholesterol depletion results in the release of the membrane-associated form of as1-casein. These experiments reveal that the insolubility of as1-casein reflects its partial association with a cholesterolrich detergent-resistant microdomain. We propose that the membrane-associated form of as1-casein interacts with the lipid microdomain, or lipid raft, that forms within the membranes of the endoplasmic reticulum, for efficient forward transport and sorting in the secretory pathway of mammary epithelial cells

Aggregation and breakup of acrylic latex particles inside millimetric scale reactors

Aggregation of acrylic latex is investigated inside tubular millireactors working under laminar hydrodynamic conditions. The size distribution and fractal dimension of aggregates are measured using light scattering. Results show that the equilibrium between rupture and aggregation is achieved quickly, allowing the study of cluster size distribution and shape at the aggregation/rupture steady state. Both laminar hydrodynamic conditions and high shear rate are suspected to promote the formation of aggregates with a high fractal dimension, which means that the particles are almost spherical, thereby offering an interesting alternative to conventional batch processes. These results can provide useful information for industries aiming at producing aggregates at specified size and quality

The Solvation Properties of the Aliphatic Alcohols

Article on the solvation properties of the aliphatic alcohols

Towards the design of an intensified coagulator

This study compares the hydrodynamics in three millimeter-scale continuous reactor geometries that can be easily used in laboratories and industries – a straight tube, a coiled tube and a Dean-Hex reactor – via numerical simulations and analyses the data in a way that is specifically relevant to coagulation processes, thereby offering insights for engineers to develop new coagulation reactors. A numerical approach based on Lagrangian particle tracking is presented to better understand the impact of the geometry and flow on properties that influence coagulation. The results show that the Dean-Hex meandering geometry provides narrower residence time and shear rate distributions, as well as higher mean average shear rates and Camp number distribution than the other geometries. This is attributed to the generation of transverse flows and radial mixing in the Dean-Hex reactor and suggests that a faster and more homogenous coagulation can be expected

Intestinal kinetics from digestion of milk proteins in humans

Objective. We aim to assess in humans the intestinal digestion of two protein fractions from milk, i.e. a soluble (SP) and non-soluble (casein; CAS) proteins, that exhibit opposite chemical and digestive characteristics

Polyadenylation of a functional mRNA controls gene expression in Escherichia coli

Although usually implicated in the stabilization of mRNAs in eukaryotes, polyadenylation was initially shown to destabilize RNA in bacteria. All the data are consistent with polyadenylation being part of a quality control process targeting folded RNA fragments and non-functional RNA molecules to degradation. We report here an example in Escherichia coli, where polyadenylation directly controls the level of expression of a gene by modulating the stability of a functional transcript. Inactivation of poly(A)polymerase I causes overexpression of glucosamine–6-phosphate synthase (GlmS) and both the accumulation and stabilization of the glmS transcript. Moreover, we show that the glmS mRNA results from the processing of the glmU-glmS cotranscript by RNase E. Interestingly, the glmU-glmS cotranscript and the mRNA fragment encoding GlmU only slightly accumulated in the absence of poly(A)polymerase, suggesting that the endonucleolytically generated glmS mRNA harbouring a 5′ monophosphate and a 3′ stable hairpin is highly susceptible to poly(A)-dependent degradation