Chemical Science Blog

Researchers in Australia have devised a new way to test how well drugs penetrate the low-oxygen core of solid tumours. ‘Hypoxic’ regions of tumours are notoriously difficult to target with drugs and the new work could help in the development of new compounds that can effectively reach these areas and efficiently kill the cells.

Tumours often grow faster than the blood vessels that supply them, and parts of the tumour therefore become starved of oxygen and grow slowly. This makes it difficult for drugs carried in the blood to reach these areas; furthermore many drugs rely on the rapid proliferation of cancer cells, so slowly growing ones are less susceptible.

One approach has been to develop ‘prodrugs’, which become toxic to the cell only upon entering the low-oxygen environment. Some of these are based upon cobalt(III) attached to a toxic ligand. In a hypoxic environment the cobalt is reduced to cobalt(II) and the ligand is released. However, there are currently no reliable ways either to visualise the hypoxic region of a tumour or to measure penetration of the drugs.

Now, Byung Kim, Trevor Hambley and Nicole Bryce at the University of Sydney have developed a three-dimensional model of a solid tumour with a hypoxic core that allows both the hypoxic region to be highlighted and the extent of penetration of prodrugs to be measured.

An assay that combines enzymatic reactions with a fluorescent sensor could help discover new Alzheimer’s disease drugs. 

Acetylcholinesterase is an enzyme involved in the development of Alzheimer’s disease. Werner Nau and Yu Liu and their teams hope that their tandem assay could be used to search for new acetylcholinesterase inhibitors as potential drugs.

The simple, fluorescence based, tandem assay can measure micromolar concentrations of choline and acetylcholine or screen for enzyme inhibitors. The change in fluorescence is easy to detect, making the assay suitable for large scale screening. 

Reference:
Operational calixarene-based fluorescent sensing systems for choline and acetylcholine and their application to enzymatic reactions
D-S Guo, V D Uzunova, X Su, Y Liu and W M Nau, Chem. Sci., 2011, DOI: 10.1039/c1sc00231g

Nanoparticle probes for imaging cells can now be made more simply and quickly thanks to a new method reported by Chinese chemists. 

Gold nanoparticles have been widely used for bio-imaging but they need to be coated, commonly in silica, to protect them and stop them aggregating. The conventional method for silica coating is time-consuming but the team say they’ve overcome this tedious process by using an organosilica source. The resulting organosilica shell has –SH and –OH groups inside it, making it easy to functionalise with fluorescent dyes or biomolecules. 

By modifying the gold core with Raman reporters and the organosilica shell with a fluorophore, the group produced nanoparticles with three modalities of imaging – Rayleigh scattering, fluorescence and surface enhanced Raman scattering.

Reference:
Au@organosilica multifunctional nanoparticles for the multimodal imaging
Y Cui, X-S Zheng, B Ren, R Wang, J Zhang, N-S Xia and Z-Q Tian, Chem. Sci., 2011, DOI: 10.1039/c1sc00242b

Covalent organic frameworks (COFs) are an emerging class of porous materials with potential for gas storage and organic photovoltaics. Their development has been hampered because the building blocks most commonly used to make them are poorly soluble and prone to oxidation.

Now US chemists have developed a general strategy for making COFs from stable, soluble starting materials. They also gained insight into the transformation’s mechanism, which should help scientists predict crystallisation conditions and prepare materials with improved properties.

Find out more in A mechanistic study of Lewis acid-catalyzed covalent organic framework formation by William Dichtel and colleagues.

UK scientists have worked out how ionic liquids solubilise cellulose, an important step in biomass processing.

The precise mechanism for the dissolution of cellulose by ionic liquids is hotly debated, with some researchers insisting that the ionic liquid cation forms a hydrogen bond to the sugar’s OH groups, without data to back it up.

Now researchers have proved conclusively with experimental data that there are no hydrogen bonding interactions between the cation and the sugars.

Read Christopher Hardacre’s Chemical Science Edge article to find out more.

Also of interest:
How polar are ionic liquids? Solutions of charge-transfer salts in ionic liquids reveal a dual nature of solvent polarity and an absence of ion pairing