Predicting Ligand-Free Cell Attachment on Next-Generation Cellulose-Chitosan Hydrogels.

There is a growing appreciation that engineered biointerfaces can regulate cell behaviors, or functions. Most systems aim to mimic the cell-friendly extracellular matrix environment and incorporate protein ligands; however, the understanding of how a ligand-free system can achieve this is limited. Cell scaffold materials comprised of interfused chitosan-cellulose hydrogels promote cell attachment in ligand-free systems, and we demonstrate the role of cellulose molecular weight, MW, and chitosan content and MW in controlling material properties and thus regulating cell attachment. Semi-interpenetrating network (SIPN) gels, generated from cellulose/ionic liquid/cosolvent solutions, using chitosan solutions as phase inversion solvents, were stable and obviated the need for chemical coupling. Interface properties, including surface zeta-potential, dielectric constant, surface roughness, and shear modulus, were modified by varying the chitosan degree of polymerization and solution concentration, as well as the source of cellulose, creating a family of cellulose-chitosan SIPN materials. These features, in turn, affect cell attachment onto the hydrogels and the utility of this ligand-free approach is extended by forecasting cell attachment using regression modeling to isolate the effects of individual parameters in an initially complex system. We demonstrate that increasing the charge density, and/or shear modulus, of the hydrogel results in increased cell attachment.

The application of design of experiments (DoE) reaction optimisation and solvent selection in the development of new synthetic chemistry.

This article outlines the benefits of using 'Design of Experiments' (DoE) optimisation during the development of new synthetic methodology. A particularly important factor in the development of new chemical reactions is the choice of solvent which can often drastically alter the efficiency and selectivity of a process. Whilst solvent optimisation is usually done in a non-systematic way based upon a chemist's intuition and previous laboratory experience, we illustrate how optimisation of the solvent for a reaction can be carried out by using a 'map of solvent space' in a DoE optimisation. A new solvent map has been developed specifically for optimisation of new chemical reactions using principle component analysis (PCA) incorporating 136 solvents with a wide range of properties. The new solvent map has been used to identify safer alternatives to toxic/hazardous solvents, and also in the optimisation of an S(N)Ar reaction.

B(OCH2CF3)3-mediated direct amidation of pharmaceutically relevant building blocks in cyclopentyl methyl ether.

The use of B(OCH2CF3)3 for mediating direct amidation reactions of a wide range of pharmaceutically relevant carboxylic acids and amines is described, including numerous heterocycle-containing examples. An initial screen of solvents for the direct amidation reaction suggested that cyclopentyl methyl ether, a solvent with a very good safety profile suitable for use over a wide temperature range, was an excellent replacement for the previously used solvent acetonitrile. Under these conditions amides could be prepared from 18 of the 21 carboxylic acids and 18 of the 21 amines examined. Further optimisation of one of the low yielding amidation reactions (36% yield) via a design of experiments approach enabled an 84% yield of the amide to be obtained.

Novel thienopyrrole glycogen phosphorylase inhibitors: synthesis, in vitro SAR and crystallographic studies.

Two series of novel thienopyrrole inhibitors of recombinant human liver glycogen phosphorylase a (GPa) which are effective in reducing glucose output from rat hepatocytes are described. Representative compounds have been shown to bind at the dimer interface site of the rabbit muscle enzyme by X-ray crystallography.