Chemical Science Blog

Incorporating selenium into a polymer backbone can improve the polymer’s electron transport and could lead to improved organic electronics, reports scientists from the UK and Australia.

Ambipolar conjugated polymers, which can transport both holes and electrons, are of great interest as a method to mimic silicon-based logic circuits. Thiophene copolymers have been shown to be good hole transporters but are let down by their ability to transport electrons. 

Replacing thiophene with selenophene results in a significant reduction in polymer band gap, enabling the polymers to effectively transport electrons as well as holes. The resulting polymers display one of the highest hole mobilities reported for any device structure.

Download the Chemical Science Edge article to find out more.

Huw Davies’ group have developed a domino sequence for the asymmetric synthesis of highly functionalised cyclopentanes.

The researchers from Emory University have combined scandium catalysis with a previously reported asymmetric rhodium-catalysed dienol formation to afford cyclopentanes in good to excellent levels of enantioselectivity. Four new stereogenic centres are formed in the reaction sequence and the cyclopentane products are obtained as single diastereoisomers.

The one-pot procedure commences with a tandem oxygen ylide formation and [2,3] sigmatropic rearrangement between racemic allyl alcohol 1 and vinyl diazoacetate 2, resulting in formation of chiral dienol 4. Upon heating, an oxy-Cope rearrangement provides enol 5 in quantitative yield albeit with slight erosion of enantiomeric excess. Subsequent tautomerisation yields ketone 6, which is primed for a scandium triflate-catalysed carbonyl ene reaction on elevation of temperature, affording the cyclopentane product.

The impressive diastereoselectivity of this reaction combined with the complexity of the enantioenriched cyclopentane products highlights the synthetic power of reactive metal carbenoids in such thoughtfully designed reaction sequences. Download Davies’ Edge article to find out more.

 Posted on behalf of Alice E. Williamson, Chemical Science web writer.

UK researchers have embarked upon a new method to create structurally diverse molecules for drug discovery.

Finding new lead compounds for drug discovery is a formidable challenge which has traditionally relied on natural product isolation and combinatorial chemistry. Despite significant investment in combinatorial chemistry, this approach has found very limited success due to a lack of chirality and structural rigidity in the compounds produced. To tackle this problem, chemists are using diversity orientated synthesis (DOS) which aims to produce compounds that are structurally diverse in shape and stereochemistry and also in functionality.

Robert Stockman from the University of Nottingham and his team have pioneered an approach that combines two-directional synthesis with tandem reactions as a tool for DOS. The starting material is a simple trifunctional, linear molecule that can be folded back on itself in a number of ways to produce a wide range of structures – like tying knots in a piece of rope.

12 products are synthesised from one molecule by combining two-directional synthesis and tandem reactions

The researchers were able to create twelve natural product-like structures from only one compound, in just fifteen reactions. Stockman and his team found that a number of compounds derived from one of the products were effective against cancer cell lines, proving that compounds synthesised by this approach are promising candidates for use in new medicines.

To find out more, watch Dr Stockman’s video and download the Chemical Science Edge article.

Scientists from India and Denmark have found a way to go one better than x-ray crystallography to examine pharmaceutical crystals at an even deeper level. Their method could be used to distinguish between polymorphs – different crystal forms – of a compound to aid in drug design. 

The team, led by Upadrasta Ramamurty and Gautam Desiraju from the Indian Institute of Science, Bangalore, and Andrew Bond from the University of Southern Denmark, have used nanoindentation to analyse two different polymorphs of aspirin. Polymorphs are crystals of the same compound but with a different molecular arrangement. Although two crystals may appear similar in structure, they can have dramatically different properties, and many drugs only receive regulatory approval for one form. ‘One of the current areas of research is trying to link crystal properties to crystal structure and to try to understand how polymorphism occurs,’ says Bond.

The nanoidentation technique involves depressing a nano-sized tip into the crystal. The researchers then measured the imprint left in the sample to determine the material’s mechanical properties, such as plasticity and elasticity (how easily a substance is deformed permanently and non-permanently, respectively).

The team discovered that two polymorph crystals of aspirin, which appeared to be pure by x-ray crystallography, in fact contained a mixture of the polymorph types. Nanoindentation could have an impact on the pharmaceutical industry, which currently relies on x-ray crystallography to establish whether or not a new drug has been made, for intellectual property rights.

Read the full story in Chemistry World and find out more by downloading the Chemical Science Edge article.

US chemists have devised an efficient synthesis of a natural product with great potential as a protectant against chemical warfare agents and in the treatment of Alzheimer’s disease.

Huperzia serrata, one of an ancient lineage of plants known as the firmosses, has been much in demand lately because it contains a chemical known as (-)-huperzine A. This alkaloid is a potent and selective inhibitor of acetylcholine esterase, and as a result is able to counteract the action of certain chemical warfare agents, such as sarin and VX. There are also strong suggestions that it may slow the progression of neurological diseases such as Alzheimer’s disease. A team of organic chemists led by Seth Herzon at Yale University, New Haven, has now developed a high-yielding route to this elusive natural product, opening up opportunities for its wider clinical evaluation.

‘The primary obstacle to the clinical development of (-)-huperzine A has been one of supply,’ says Herzon. He points out that the average yield from the dried herb is just 0.011 per cent, a problem compounded by the nearly 20 years it takes to reach maturity, coupled with its increasing scarcity due to overharvesting in its native China.  To address these problems, several groups have in the past devised syntheses of (-)-huperzine A, with the best to date employing 16 steps and giving an overall yield of about 2.8 per cent. Herzon and his team have now beaten this by a factor of 16, with an eight-step synthesis that gives 25-45 per cent overall yield.

Read the full story in Chemistry World and download Herzon’s Chemical Science Edge article.

A team of researchers led by Takashi Nakanishi from the National Institute for Materials Science in Japan have made a nanocarbon hybrid of a C₆₀ derivative and single-walled carbon nanotube (SWCNT) to be used in photovoltaic devices.  The high performance of the nanomaterial is the result of a combination of the optical and electronic properties of the SWCNTs with the electron-accepting property of C₆₀.

Photoconductivity experiment using a field-effect transistor equipped with the carbon nanohybrid

The C₆₀ is decorated with long alkyl chains which have an affinity for the SWCNT surface, avoiding the problems associated with covalent functionalisation when combining such materials. By incorporating C₆₀ into the hybrid, the SWCNTs were soluble in organic solvents meaning classic wet processes can be used to fabricate the photovoltaic device.

The nanocarbon material also has the added benefit of being superhydrophobic, providing the device with waterproof properties.

 To find out more about this research, read the Chemical Science Edge article.

Scientists have found that the way ice bonds to metal does not obey the ‘ice rules’. Andrew Hodgson, together with teams from the UK and Spain, wanted to understand water–metal and hydroxyl–metal interactions, to devise molecular models of wet metal interfaces for studying catalytic and electrochemical reactions that occur on these types of surfaces.

Using scanning tunnelling microscopy and density functional theory calculations, the teams produced a phase diagram for water and hydroxyl on a copper surface, providing a complete molecular description of the complex hydrogen bonding structures formed. They saw three distinct phases as the temperature was decreased and the water/hydroxyl ratio increased: pure OH dimers, extended 1H₂O:1OH chains aligned along the close-packed Cu rows, and finally a distorted 2D hexagonal c(2 × 2) 2H₂O:1OH network.

Binding geometry and simulated STM images for (a) an isolated OH group, (b) an OH dimer and (c) an array of OH forming a dimer chain on the copper surface

None of these phases obey the conventional ‘ice rules’. Instead, their structures can be understood based on weak H donation by hydroxyl, which favours H-bonding structures dominated by water donation to hydroxyl, and competition between hydroxyl adsorption sites.

Found out more by downloading the Chemical Science Edge article.