Chemical Science Blog

Understanding the way ions behave in the gas phase is important for solving atmospheric, astrochemical and biological problems. In Chemical Science’s latest Mini review, Arthur Suits, at Wayne State University, Detroit, US, and colleagues illustrate how high-resolution ion and electron imaging techniques can be used to study photofragmentation and photoionisation dynamics in ions. Examples discussed include the use of cation photodissociation to explore the upper atmosphere of Titan, Saturn’s largest moon.

Interested? Find out more…

US chemists have synthesised an entire family of marine alkaloids that show potent anticancer activity and potential for treating Alzheimer’s disease.

Mohammad Movassaghi and colleagues at Massachusetts Institute of Technology, Cambridge, were intrigued by the molecular architecture of agelastatin alkaloids, in particular the cyclopentane C-ring, which others had proposed is formed at an early stage in the alkaloid’s biosynthesis. Conversely, Movassaghi envisaged a biosynthetic sequence where the C-ring forms at an advanced stage of the synthesis and so he designed a total synthesis plan inspired by his biogenetic hypothesis.

This unique approach gave Movassaghi access to all known members of this alkaloid family. Although 10 different research groups had made agelastatin A before, Movassaghi’s route was the shortest, most efficient and largest scale synthesis to date, generating over 1.4 g of the highly potent antitumour agent.

To find out more about the new transformations developed, including an imidazolone-forming annulation reaction and a carbohydroxylative trapping of imidazolones, read the Chemical Science Edge Article.

A new, fast way to analyse DNA has been developed by European scientists that could be used to sequence the genomes of viruses and in the future help tackle genetic disorders such as schizophrenia and congenital heart defects. 

Current DNA sequencing methods are able to sequence short regions of the genome (30² to 1500² bases in length). Regions that are either duplicated or deleted relative to a reference genome are an important cause of structural variation in the human genome with links to a variety of genetic disorders. Using current sequencing methods, studying these repeats is time consuming and labour intensive. 

Now, Robert Neely and colleagues, at Catholic University Leuven, Belgium, have used a DNA methyltransferase enzyme to label the 5′-GCGC-3′ DNA sequences with a fluorescent marker. Immobilising and stretching the DNA on a surface then produces a unique and reproducible pattern when combined with the fluorescent markers. The result is a ‘fluorocode’ – a simple description of the DNA sequence, which can be read and analyzed like a barcode. 

Sequences of DNA are tagged with a fluorescent marker

DNA barcodes using fluorescent tagging can be read quickly as labelled samples pass a detector, but Neely’s fluorocode gives significantly enhanced resolution and uses a much smaller number of DNA molecules. ‘The method from unlabelled DNA to fluorocode can be achieved in less than 8 hours for a DNA molecule that is around 50000 bases in length,’ says Neely. Current single molecule mapping methods have a timeframe of around one week for analysing individual genomes. 

Kalim Mir, an expert in DNA sequencing and genomics at the Wellcome Trust Centre for Human Genetics, University of Oxford, comments, ‘the advantage the system has over conventional optical mapping is that it can provide ultra-high density mapping of genomic DNA and could easily be extended to much longer fragments from larger genomes, from bacteria to humans. The most significant challenge the authors face is to scale the technique up to the human genome.’ 

The group now plan to scale the fluorocode up from viral genomes to bacterial and on to eukaryotic genomes with the immediate aim of producing multi-coloured fluorocodes with even more detail. 

Carl Saxton

Find out more in the Chemical Science Edge article.

Carbon nanotubes can now be functionalised on a large scale more cleanly and efficiently than before, improving their commercial viability for engineering, catalysis and bionanotechnology.

Milo Shaffer, at Imperial College London, and colleagues, have exploited existing surface oxide defects present in most carbon nanotubes to attach a variety of organic molecules to their surfaces. Surface functionalisation can improve a nanotube’s compatibility with particular environments, such as electrolytes, or can provide a direct function, such as catalytic activity. Conventional functionalisation methods are time-consuming and inconvenient. They also generate a lot of liquid waste, commonly toxic or corrosive. Although some solvent-free methods are known, they are poorly reproducible and often degrade the graphite framework and affect the nanotube’s intrinsic properties.

Shaffer heated the nanotubes to 1000 ºC under an inert atmosphere, which caused the defect groups to desorb, leaving reactive surface radicals. When he added functional monomers, such as vinyl compounds, to the activated nanotubes, the monomers polymerised, forming oligomers grafted to the nanotube surface.

This thermochemical method can be applied entirely in the gas phase, which simplifies work-up, improves scalability and makes it compatible with existing gas phase processes for commercially producing nanotubes.

Read the full Chemical Science Edge Article to find out more.

Gene therapy has the potential to revolutionise personal medicine but delivering the genes into cells is a major challenge. Dendrons offer a potential solution as their many ligands bind strongly to DNA but now scientists are reporting that smaller dendrons with fewer ligands can actually be better at gene delivery than larger ones. 

Previous studies show that larger dendrons bind DNA more strongly than smaller ones because they have a higher positive charge and form more contacts with the DNA. But as large dendrons are more difficult to synthesise, David Smith, at the University of York, UK, and colleagues have been investigating other ways to improve dendron–DNA interactions.

The team designed spermine-functionalised dendrons capable of self-assembling then used multiscale modelling to understand the impact of the self-assembly process on their ability to bind and deliver DNA. Surprisingly, the smaller dendrons were better at binding DNA because they self-assembled more effectively to form an aggregate with a higher charge density. Also, two hydrophobic cholesterol units (rather than one) at the dendron focal point resulted in enhanced gene delivery in vitro. These dendrons assemble into a different shape and pack DNA more effectively, says Smith.

To find out more, read the Edge article.