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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 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

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.

Spongistatin 1 is a highly cytotoxic natural product derived from a marine sponge.  In addition to its exquisite biological activity against human cancer cell lines, the structural complexity of spongistatin 1 has captured the imagination of several organic chemistry groups.

A number of total syntheses of the spongistatins exist, but more recently, simplified analogs of the natural products have been tested for anti-cancer activity.

In order to further probe the biological efficacy of simplified spongistatin analogs– or indeed, fragments– researchers at Columbia University have developed new methodology for the synthesis of the A-B fragment 3 and its merger to the C-D spiroketal fragment 3.

In their most recent Chemical Science Edge article, the Leighton research group have described a synthetic blueprint that could enable the synthesis and testing of a library of ‘C-D spiroketal-modified’ analogs of spongistatin 1.  Towards this overarching goal, Samuel Reznik was able to synthesise 34.5 g of fragment 3 in around 60 days; an achievement that demonstrates both the ‘scalability and step-economy’ of this synthetic route.

The Leighton group hope to apply this route to the synthesis of a series of C-D analogs and also hope to develop a complementary synthesis of the E-F fragment to further explore the anti-cancer therapeutic potential of spongistatin 1 derivatives.

Marilyn Monroe once sang that ‘diamonds are a girl’s best friend.’  If that is the case then it could be said that graphene, another form of carbon, has become the scientist’s best friend.  The relatively recent explosion of research conducted on graphene has been remarkable, and in 2010 resulted in a Nobel Prize for Andre Geim and Konstantin Novoselov at the University of Manchester.

Energy minimized structure from DFT calculations for a large PAH with the hydrogens removed.

Graphene can be thought of as the largest member of the polycyclic aromatic hydrocarbon (PAH) family, molecules made up of fused aromatic rings.  The interest in these carbon-based materials arises from their amazing electronic and optical properties.  The smaller members of the PAH family provide chemists an opportunity to create molecules of fixed and uniform dimensions, something which is challenging when making graphene.  Furthermore, by synthesising PAHs in a logical, stepwise fashion, we can adapt their properties to suit our own needs.

In a recent Chemical Science Edge article, the groups of Hexing Li (Shanghai Normal University) and Colin Nuckolls (Columbia University) have shown that they can construct large polycyclic aromatic hydrocarbons (PAHs) in a relatively straightforward and high yielding process. As might have been expected, such a large aromatic molecule is not particularly soluble but, emphasising the utility of their method, they are able to overcome this by adding groups to the molecule which make it more soluble.  The versatility of their approach will surely lead to the creation of even larger PAHs which will eventually serve to bridge the gap between these small molecules to the extended structures of graphene.

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

Supersized contorted aromatics
Shengxiong Xiao, Seok Ju Kang, Ying Wu, Seokhoon Ahn, Jong Bok Kim, Yueh-Lin Loo, Theo Siegrist, Michael L. Steigerwald, Hexing Li and Colin Nuckolls
Chem. Sci., 2013, 4, 2018-2023
DOI: 10.1039/C3SC50374G

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.

Chloride ions are central to many biological processes and measuring the concentration of chloride ions in biological fluids can help diagnose a number of diseases, including cystic fibrosis.

Scientists from the US have synthesised a squaraine rotaxane which can detect chloride ions via colorimetric naked eye detection and fluorescence. This is the first example of a ratiometric chloride sensor that emits in the deep red region.

Read the ‘HOT’ Chemical Science article for free:

Squaraine rotaxane shuttle as a ratiometric deep-red optical chloride sensor
Carleton G. Collins, Evan M. Peck, Patrick J. Kramer and Bradley D. Smith
Chem. Sci., 2013, DOI: 10.1039/C3SC50535A