Chemical Science Blog

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.

Photochemical HX splitting reactions (X = halogen) provide a route for solar-to-fuel energy conversion and halogen photoelimination is a critical step in the process.

Scientists in the US have investigated the photoreduction mechanism of a pair of valence-isomeric dirhodium phosphazane complexes and suggest that a common intermediate is accessed in the photochemistry of both mixed-valent and valence-symmetric complexes.

They conclude that halogen photoelimination proceeds by two sequential photochemical reactions: ligand dissociation followed by subsequent halogen elimination, and they hypothesise that complexes that can directly assume a halide-bridged structure will have the highest quantum efficiencies for energy conversion.

Read the ‘HOT’ article for free today:

Halogen Photoelimination from Dirhodium Phosphazane Complexes via Chloride-Bridged Intermediates
David C Powers, Matthew B Chambers, Thomas S Teets, Noémie Elgrishi, Bryce L Anderson and Daniel G Nocera
Chem. Sci., 2013, DOI: 10.1039/C3SC50462J

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.

Scientists in the UK are attempting to understand the host–guest chemistry of molecular cages in solution, by separately quantifying the free energy contributions of (at least) three host–guest interaction mechanisms that usually work in unison: hydrogen-bonding, non-polar interactions and solvophobic effects.

The team have systematically looked at a series of guests (with/without π-stacking ability and different hydrogen-bond acceptor capabilities), within a water-soluble cubic coordination cage and an isostructural organic-soluble cage.

Being able to quantify solvent effects associated with specific molecular substituents or functional groups will help in the design of hydrophobic cavities within coordination cages. Hydrophobic cavities can stabilise otherwise unstable molecular guests and catalyse reactions where the transition state matches the cavity size and shape.

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

Quantification of solvent effects on molecular recognition in polyhedral coordination cage hosts
Martina Whitehead , Simon Turega , Andrew Stephenson , Chris Hunter and Mike D Ward
Chem. Sci., 2013, Accepted Manuscript
DOI: 10.1039/C3SC50546D

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

In a recent Edge article, Chemical Science Associate Editor Professor Haw Yang and his group at Princeton University use Brownian motion to transport a two-sided micro-particle to a target, with the help of ‘photon-nudging’ to keep it on track.

The micrometer precision of this simple method of locomotion is notable.  It could potentially be used to deliver drugs and molecules in cells, precisely and in real-time.

Normally, Brownian motion causes micro-particles to move randomly in fluids.  This presents a challenge for the creation of controllable ‘micro-swimmers’.  Yet, with some external direction, this motion can deliver particles to their targets.

The adaptive photon-nudging idea.

Yang and co-workers ‘steer’ a two-sided microsphere in a fluid, as it undergoes Brownian motion.  One side has a gold coating, whilst the other is polystyrene.  When the polystyrene side is facing the target, a laser beam is activated.  The light then moves this ‘Janus’ particle in one of two ways, either by ‘radiation-pressure’ (pushing by photons) or by heat-induced locomotion via the photophoretic effect.  The latter effect forces this particle, when it has a large temperature difference across its two faces, to move in the direction of the cooler side (polystyrene side) (see also Crooke’s radiometer).

The authors do not use ‘photon-nudging’ constantly.  It is used occasionally, just to steer the particle in the right direction. Brownian motion does most of the work transporting the particle to the target– making this a good example of a man-made Brownian motor.

It will be interesting to see how soon researchers can refine this ‘photon-nudging’ method to achieve nanometer or molecular scale accuracy.  Many would welcome that level of control for particles and molecules in cells and chemical solutions.

Read this HOT Chem Sci cover article in full!

Harnessing thermal fluctuations for purposeful activities: the manipulation of single micro-swimmers by adaptive photon nudging
Bian Qian, Daniel Montiel, Andreas Bregulla, Frank Cichos and Haw Yang
Chem. Sci., 2013, 4, 1420-1429
DOI: 10.1039/C2SC21263C

Geoff Nelson is a guest web-writer for Chemical Science.  He currently works as a post-doctoral research associate in Dr David Payne’s research group in the Department of Materials at Imperial College, London.  Geoff’s current research concerns the synthesis and characterization of post-transition metal oxides for use in the energy sector.  His other research interests include carbon-based materials, biophysical chemistry, and surface science.