Chemical Science Blog

In this Chemical Science Edge article, researchers from the Center for Research in Biological Chemistry and Molecular Materials (CIQUS) and Department of Organic Chemistry at the University of Santiago de Compostela, describe a highly elegant method of controlling and changing the helical sense and elongation of poly(phenylacetylene)s.  This is achieved via modifying the polymer backbone with a chiral group which responds to different solvent environments in a reliable way.  The system seems ideal for chemical sensor technology development.

The polymer highlighted in the article is a poly(phenylacetylene) derivatised with a chiral methoxytrifluoro-phenylacetic acid (MTPA) group.  The monomer was prepared from the alkyne 4-ethynylaniline, (R)-α-methoxy-α-(trifluoromethyl)phenylacetic acid and oxalyl chloride in two steps.  Subsequent polymerization was carried out using a rhodium norbornadiene dimer catalyst, under argon, and the polymer was precipitated from a tetrahydrofuran (THF) solution using methanol and hexane.

The key to the effects described in changes to the polymer properties is due to the chemical structure of the pendant group, which contains an amide and a chiral centre, giving rise to four stereoisomers.  The amide group function can result in cis or trans geometry, and the carbonyl and chiral centre yield syn (sp) or anti-periplanar (ap) conformers.

In a range of solvents, the resultant 4 states of this moiety have profound and different effects on the elongation and the sense (or direction), and tightness (compression or elongation), of the helical polymer.  The effect is shown here:

Solvent donor effects which destabilise the amide group to a cis orientation were proven by UV-Vis spectroscopy to elongate and change the sense of the helicate.  A bathochromic shift was observed.  The authors suggest that solvent polarity plays a greater role with the carbonyl-methoxy group in changing the sense (or direction) of the helicate, via circular dichroism measurements. Overall, any destabilisation in the pendant group is accomodated in the polymer backbone, via a change in the orientation and elongation of the helicate, resulting in a new stable state.

Sequential stimulation of the two functional groups was performed, as were experiments using thin films of the polymer. A large amount of analytical data: IR, NMR, UV-Vis, Raman spectroscopy and differential scanning calorimetry (DSC) is presented, as are atomic force microscopy (AFM) measurements and findings from molecular mechanics calculations.

This work should prove of interest to polymer chemists and sensor researchers alike, and to the wider scientific community.

Controlled Modulation of the Helical Sense and Elongation of Poly(phenylacetylene)s by Polar and Donor Effects
Ricardo Riguera, Felix Freire, Seila Leiras, José Manuel Seco and Emilio Quiñoá
Chem. Sci., 2013, Accepted Manuscript
DOI: 10.1039/C3SC50835H

Kevin Murnaghan is a guest web-writer for Chemical Science. He is currently a Research Chemist in the Adhesive Technologies Business Sector of Henkel AG & Co. KGaA, based in Düsseldorf, Germany. His research interests focus primarily on enabling chemistries and technologies for next generation adhesives and surface treatments. Any views expressed here are his personal ones and not those of Henkel AG & Co. KGaA.

Scientists in the US have made two fluorescent probes that can distinguish persulfides and polysulfides from hydrogen sulfide. This work paves the way for developing non-destructive probes for sulfane sulfurs that can be used in living cells and even in vivo.

Fluorescence image of a polysulfide in H9c2 cells

Sulfane sulfurs – which feature divalent sulfur atoms bonded to other sulfur – appear in a number of biologically important compounds. They include thiocysteine and thiocystine, two products of cysteine metabolism which are found at higher than normal concentrations in cancer cells. Until now, the only selective methods for detecting sulfane sulfurs were destructive and could therefore not be used for real-time imaging.

Now, Ming Xian and colleagues at Washington State University have designed a probe for sulfane sulfurs and tested it on living cells.

Continue reading the full article in Chemistry World »

Read the original journal article in Chemical Science:
New fluorescent probes for sulfane sulfurs and the application in bioimaging
Wei Chen, Chunrong Liu, Bo Peng, Yu Zhao, Armando Pacheco and Ming Xian  
Chem. Sci., 2013, Advance Article
DOI: 10.1039/C3SC50754H, Edge Article

Scientists from the Netherlands show how supramolecular polymers can be used to steer the assembly of proteins in a reversible, dynamic manner.

Synthetic supramolecular polymers have already shown great potential in the materials field, but their potential to target biological systems has been underexplored until now. This is surprising considering their self-assembling nature, providing access to structures and molecular properties analogous to biological systems.

The synthesis of a mono-functional discotic molecule, forming supramolecular columnar polymers, allows for the site-selective, covalent attachment of proteins. The supramolecular polymer, displaying the proteins along the columns, acts as a dynamic framework; the simultaneous conjugation of two different proteins enables their assembly in close proximity, resulting in efficient energy transfer. The dynamic nature of the protein-conjugated discotic monomers in the supramolecular polymers allows the exchange of supramolecular building blocks between the columns and tuning of protein density.

The concept of supramolecular polymers displaying proteins could bridge the gap between synthetic and biological systems, providing entry to create dynamic multi- and heterovalent protein assemblies with a responsive nature.

Read the ‘HOT’ Chemical Science article:

 Dynamic and bio-orthogonal protein assembly along a supramolecular polymer
Katja Petkau-Milroy, Dana A. Uhlenheuer, A. J. H. Spiering, Jef A. J. M. Vekemans and Luc Brunsveld
Chem. Sci., 2013, Advance Article, DOI: 10.1039/C3SC50891A

Controlling polymer debonding/rebonding properties using responsive materials is an exciting emerging area of chemistry and it is widely accepted that control of these properties can be achieved by engineering the functional end-groups responsible for monomer dynamic bonding.

Scientists in Germany and Australia report that the control of the bonding/debonding properties in materials obtained by Diels–Alder reactions between difunctional polymeric building blocks can also be governed by entropy considerations such as chain length and branching of the building blocks. They have shown this theoretically and experimentally for two Diels–Alder polymer systems, each based on a different difunctional diene and a common difunctional dienophile.

This interesting finding will help polymer and materials chemists transform the approach they take to designing reversibly/dynamically bonding materials and could aid the development of self-healing materials.

Read this ‘HOT’ Chemical Science article, hot off the press:

Harnessing entropy to direct the bonding/debonding of polymer systems based on reversible chemistry
N K Guimard et al, Chem. Sci., 2013, DOI: 10.1039/c3sc50642h

Otto Warburg was a rather interesting man; not only was he a Nobel prize winner, he was BFFs with Einstein, served in the cavalry in the war, and also insisted using his own tea bags when he went out for a cuppa.  Otto also observed that cancerous tissues consumed rather large amount of glucose compared to non-cancerous tissues and also had high rates of aerobic glycolysis.  These observations, now known as the Warburg effect, are now recognised as some of the hallmarks of cancer.

A recent Chemical Science Minireview by Emilia Calvaresi and Paul Hergenrother focuses on the current progress and future directions of exploiting the Warburg effect by targeting it for cancer treatment.  One potential strategy is glycoconjugation; simply put, the linking of a drug to a sugar.  Unfortunately, however, it is not as simple as dipping a fun-size Mars bar in some cisplatin.

The strategy for glycoconjugation of anticancer drugs was inspired by the use of 18F-FDG, a radiolabeled glucose analogue used to visualise tumours.

Like a rather strange cake recipe book, this review discusses ways to make sugary, anticancer conjugates– it does mention sugar and mustard at one point– but more seriously, it explains the developments in this anticancer approach, the difficulties and the lessons learned, in a clear and comprehensible way.

Since the first report of glycoconjugated anticancer drugs in 1995, this field has rapidly developed to the point that one conjugate (glufosfamide) is already in advanced trials, and Calvaresi and Hergenrother discuss this, as well as other anticancer glycoconjugates that are in development.

Importantly, Calvaresi and Hergenrother recognise that, for these glycoconjugated anticancer compounds to be successful, there are outstanding issues that need addressed, i.e., what is the best way to make the cancer ‘eat up’ these conjugates?  Do you offer it the dark chocolate or the milk chocolate?  Which position on the sugar should be substituted?  Are their more effective sugars?  What’s the best way to test the efficacy, i.e., how do we measure how much the cancer has eaten, and if it likes it?

The authors conclude that this field has a great deal of potential but, just like any new confectionery, it needs to be rigorously developed at each stage for optimum customer satisfaction.

Read this HOT Chem Sci Minireview in full!

Glucose conjugation for the specific targeting and treatment of cancer
Emilia C. Calvaresi and Paul J. Hergenrother
Chem. Sci., 2013, Advance Article
DOI: 10.1039/C3SC22205E

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, to become an assistant editor at the BMJ Publishing Group. When not trying to explain science through ridiculous analogies, you can often find her crocheting, baking or climbing, but not all at once.