Chemical Science Blog

The anticancer drug cisplatin has revolutionised cancer chemotherapy. Its ability to effectively treat a wide range of cancers has made this drug a popular therapeutic choice but the side effects can be severe, including possible damage to the kidneys and nervous system. Researchers have been trying to avoid these side effects by designing systems to deliver the cisplatin to the target area, where it can be released to selectively destroy the cancer tissue.

Promising delivery vehicles for platinum-based drugs include liposomes, polymers and dendrimers, organic macrocycles, nanoparticles, viruses and carbon nanotubes. Now, James Crowley’s group at the University of Otago, New Zealand, have reported the first example of cisplatin inclusion in a metallosupramolecular cage.

Two cisplatin molecules are bound within the cage and can be released on demand by introducing Cl^– or 4-dimethylaminopyridine (DMAP). These ligands compete for binding with the cage Pd^II centres and induce dissociation of the cage structure. If the cage is deconstructed using Cl^–, it can be reassembled by adding Ag⁺ ions, which precipitate the Cl^– out of the system and allow the cage to re-form. This is particularly impressive since there are few reported examples of stimulus-induced cage assembly and disassembly. This controllable uptake and release of a drug molecule shows that similar systems may have real application for drug delivery in the future.

To find out more about Crowley’s metallosupramolecular cage, read the full article.

Posted on behalf of Cally Haynes, Chemical Science web writer.

The RSC Macrocylic and Supramolecular Chemistry meeting (MASC-11) is taking place on the 19^th and 20^th December 2011 at the University of Bath, UK.

A number of high profile authors will be speaking at the meeting including Chem Soc Rev Associate Editor, Professor Phil Gale, and Professor Kay Severin who is giving the Chemical Science sponsored lecture. To find out more about Professor Severin’s research, download his latest Chemical Science articles:

• Dative boron–nitrogen bonds in structural supramolecular chemistry: multicomponent assembly of prismatic organic cages
• Constitutionally selective amplification of multicomponent 84-membered macrocyclic hosts for (−)-cytidine•H⁺

Dr Jonathan Nitschke will be delivering the Dalton Transactions lecture as a result of being awarded the 2011 Dalton Transactions European/African Lectureship earlier on this year. Jonathan has also recently been awarded the ChemComm 2012 Cram Lehn Pedersen award.

Read more about Jonathan’s research by downloading his Chemical Science articles: 

• Selective anion binding by a “Chameleon” capsule with a dynamically reconfigurable exterior 
• Reactivity modulation in container molecules.

ChemComm, Chemical Science and Chem Soc Rev Deputy Editor, Joanne Thomson, will be attending the event. If you would like to arrange a meeting with Joanne, please email her at the Editorial Office.

To attend MASC-11, register before the 12^th December 2011. The deadline for poster abstract submissions is 1^st December.

Rotaxanes are dumbbell-shaped molecules that are threaded through a separate macrocylic molecule. The two molecules are not chemically bonded to one another but instead are mechanically interlocked – a feature that can be exploited for molecular switches in molecular electronics, actuators and controlled drug release.

In a quest to understand the spatial requirements of these molecules, Suvankar Dasgupta and Jishan Wu from the National University of Singapore have discovered the lightest rotaxane to date. The rotaxanes in question were composed of a dibenzylammonium ion which was threaded through crown ether molecules of various sizes. As a result of their investigations, Dasgupta and Wu found that a [20]crown ether was capable of encompassing the dibenzylammonium dumbbell.

To find out more about this research, download the Chemical Science article today.

Also of interest…

Visit the ChemComm Supramolecular web theme issue for lots more on Rotaxane structures.

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.