Chemical Science Blog

Lift your right foot off the floor and make clockwise circles with it. Managing comfortably? Now draw a ‘6’ in the air with your right hand – what’s happened to your foot? It’s all gone a bit wrong, hasn’t it? See, it isn’t that easy to do two different things at once. Another example of this is the dual labelling of proteins; however, Stephen Caddick and colleagues appear to have got on top of this, as reported in their recent paper in Chemical Science.

The dual labelling of proteins has the potential to enable studies of protein structures and the construction of theranostics, for example; however, proteins can be complex and modifications are often restricted to the N- and C-termini, limiting their usefulness. Modification of non-terminal positions is tricky and can be slow, expensive and unrewarding. Caddick and colleagues demonstrate a novel approach to site-selective labelling of proteins, which yields a dual-labelled product by the introduction of two cysteine mutants into the sequence, which are converted by a single chemical reagent into two distinct products for modification. One residue, with an accessible alpha-proton, readily forms dehydroalanine, and the other residue persists, by shielding, as a sulfonium that undergoes chemoselective ring opening by reaction with an azide group. Both groups can then be further labelled orthogonally by the desired molecules.

The group demonstrated their technique by modifying GFP (green fluorescent protein). After incorporation of the cysteine mutants and treatment with a chemical reagent (2, 5-dibromohexanediamide), further treatment with sodium azide generated dual modified GFP. Further reaction with an alkyne modified dye and mercaptoethanol yielded a rhodamine dye and thiol-labelled protein.

The researchers have demonstrated a site- and chemoselective method, which they say offers a facile and generally accessible technique for dual labelling. And now they’ve got to grips with that, I pose the ultimate test: to come up with a facile method for standing on one leg and drawing a ‘6’ – trying to do that and type this blog has also been pretty challenging.

Once you’ve tried out some one-legged multi-tasking, sit back down and read this Open Access Edge Article to see what Sarah’s talking about:

A novel approach to the site-selective dual labelling of a protein via chemoselective cysteine modification
Ramiz I. Nathani, Paul Moody, Vijay Chudasama, Mark E. B. Smith, Richard J. Fitzmaurice and  Stephen Caddick
Chem. Sci., 2013, 4, 3455-3458
DOI: 10.1039/C3SC51333E

Sarah Brown is a guest web-writer for Chemical Science.  Sarah hung up her lab coat after finishing her PhD and post-doctorate in nanotechnology for diagnostics and therapeutics and now works in scientific publishing. When not trying to explain science through ridiculous analogies, you can often find her crocheting, baking or climbing, but not all at once. All views are her own.

Palladium-catalyzed heteroallylation of unactivated alkenes – synthesis of citalopram
Joanne F. M. Hewitt, Lewis Williams, Pooja Aggarwal, Craig D. Smith and David J. France
Chem. Sci., 2013, 4, 3538-3543
DOI: 10.1039/C3SC51222C, Edge Article

Free to access until 25th August 2013

Seeing through solvent effects using molecular balances
Ioulia K. Mati, Catherine Adam and Scott L. Cockroft
Chem. Sci., 2013, Advance Article
DOI: 10.1039/C3SC51764K, Edge Article

Free to access until 25th August 2013

Click here for more free HOT Chemical Science articles for July!

Heterogeneous catalysis is widely used industrially to assist in the production of many man made materials.  The world economy is reliant upon production of these materials, therefore catalysts which are reliable and cheap are hugely important.  Heterogeneous catalysts generally fulfill these criteria, hence their wide application, but the understanding of how they function is often poorly defined.

Academic investigations of single site homogeneous catalysts are generally simpler to study, which makes defining what reactions occurs at each stage and the factors which influence them clearer to interpret.  Heterogeneous catalysts are more complex to study.  The interaction between the different phases must be considered along with the nature of the catalyst itself.  The catalysts are generally solid materials whose bulk composition may not provide an accurate picture of the surface where the reactions will ultimately be occurring and the activity may be quite different.  Analysis of the subtleties of what is happening at the surface is incredibly difficult with many of the commonly used techniques not capable of providing the detail required.  But in order to fully understand a heterogeneous catalyst it is essential to have an understanding of the how the separate phases interact.

Tristan Youngs of the ISIS Facility, Christopher Hardacre of Queen’s University Belfast, and their co-workers have reported a new method to study a heterogenous process in real time.  Neutron scattering experiments (which were only made possible by the state of the art facilities at ISIS) provide the ability to simultaneously examine the rate at which reactions occur and also the speed with which the different phases in a heterogeneous system can interact.  A commonly held principle of heterogeneous catalysis is that by constructing pores and channels in the catalyst we can increase the effective surface area of the catalyst, increasing the number of sites where reactions can occur, thereby increasing the effectiveness of the catalysts.

This study, for the first time, highlights that the speed of the process is critically dependent on how easily the molecules can pass in and out of these pores.  While this may not be the case for every process, challenging some of these commonly held beliefs will surely lead to a rethink of how catalysts are designed in the future.

Interested in more?  Read this HOT, Open Access Chem Sci Edge article now!

Probing chemistry and kinetics of reactions in heterogeneous catalysts
Tristan G. A. Youngs, Haresh Manyar,  Daniel T. Bowron,  Lynn F. Gladden and Christopher Hardacre
Chem. Sci., 2013, Advance Article
DOI: 10.1039/C3SC51477C

Ruaraidh McIntosh is a guest web-writer for Chemical Science.  His research interests include supramolecular chemistry and catalysis.  When not working as a Research Fellow at Heriot-Watt University, Ruaraidh can usually be found in the kitchen where he has found a secondary application for his redoubtable skills in burning and profanity.