Organic & Biomolecular Chemistry Blog

For [2]rotaxanes to have viable applications in molecular electronics, full control over the shuttling kinetics of the ring molecule is necessary.  J. Fraser Stoddart from Northwestern University and colleagues have shown that introducing reducible, positively-charged moieties into the rod structure effectively creates ring shuttling ‘speed bumps’.

The team synthesised degenerate [2]rotaxanes  incorporating positively bispyridinium derivatives and two 1,5-dioxynaphthalene (DNP) units on the rod portions of their dumbbell components, encircled by a single cyclobis(paraquat-p-phenylene) tetracationic (CBPQT4+) ring.  By partially reducing the conjugated bipyridinium ring, the electrostatic barrier to shuttling is removed, and the ‘speed bump’ now acts as a further recognition site.  The [2]rotaxane also becomes bistable.

The shuttling of the ring is redox controlled and fully reversible; the group hope that this type of redox-active bistable molecule may pave the way to developing candidates for the next generation of molecular electronic devices.

This interesting HOT article is currently free to access until the end of March:

Degenerate [2]rotaxanes with electrostatic barriers
Hao Li, Yan-Li Zhao, Albert C. Fahrenbach, Soo-Young Kim, Walter F. Paxton and J. Fraser Stoddart
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB00937G

Illustration of signal control through self-assembly of aromatic chromophores in a molecular beacon (MB). Generation of the fluorescence signal is controlled by conformational rearrangement of the multichromophoric assembly of alkynylpyrene (Y) and PDI (E) building blocks

Hairpin-shaped oligonucleotide probes known as molecular beacons, are comprised of a loop of target recognition sequence and a stem which contains the fluorophore and quencher.  Binding of a target oligonucleotide results in fluorescence, so a key property of a molecular beacon is the ability to efficiently quench the signal in the first place to allow sensitive target detection.

Robert Häner and co-workers from the University of Bern have carried out an detailed study on the properties of the molecular beacon stem which affect signal control.  They have previously reported that DNA strands modified with with pyrene and perylendiimide (PDI) show excellent quenching properties and here extend the work to show that self-assembly of the fluorophores is responsible.

They demonstrate that eximer fluorescence is efficiently quenched by formation of π-stacked pyrene/PDI  aggregates with the pattern EYEY, and that longer base pair stem also yield higher quenching efficiencies. The group hopes the concept of directed assembly of non-nucleosidic chromophores will be useful for other types of fluorescent  switching systems.

Read the full details of this careful study online – the article is free to access until the end of March

Signal control by self-assembly of fluorophores in a molecular beacon—a model study
Sarah M. Biner, Dominic Kummer, Vladimir L. Malinovskii and Robert Häner
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB01132K, Paper

Qing-min Wang and colleagues at Nankai University, China, describe the first complete synthesis of a recently identified natural product with intriguing anticancer activity.

Papilistatin was isolated from a Taiwan butterfly in 2010 and was found to inhibit leukaemia cell growth. This inspired Wang to undertake the synthetic challenge of producing the compound in the lab. Constructing the phenanthrene ring system proved tricky explains Wang but after many attempts at oxidative coupling, he discovered that radical cyclisation was the key.

 Read more about this synthesis in the article which is free to download until 31^st March.

First total synthesis of Papilistatin
Meng Wu, Ling Li, An-Zheng Feng, Bo Su, De-min Liang, Yu-xiu Liu and Qing-min Wang
Org. Biomol. Chem., 2011, DOI: 10.1039/C0OB01214A,

When facing the synthesis of highly electron deficient monoaryl, di-aryl and bis-diaryl acetonitriles, Christopher Gorman and his research group at North Carolina State University look at two different methods: Nucleophilic aromatic substitution (NAS) and palladium-mediated coupling.

In their search for the most efficient method, they show that palladium-mediated coupling is more efficient than nucleophilic aromatic substitution for cyano-containing, electron deficient molecules. They further show that choice of solvent, base and supporting ligand has a large effect on the yield of this coupling.

Read all of this in this HOT article that is free to access until the 31st March.

Overcoming challenges in the palladium-catalyzed synthesis of electron deficient ortho-substituted aryl acetonitriles
Molly C. Brannock, William J. Behof, Gregory Morrison and Christopher B. Gorman
Org. Biomol. Chem., 2011
DOI: 10.1039/C0OB00903B

Drug design and discovery in a research lab is already a very challenging task. It involves knowledge, intensive research, resources, a bit of luck and a lot of time. However, eureka moments do happen and when they happen it feels great.

However, the story does not finish there. One thing is the synthesis of a new drug in a lab (mg scale) but being able to scale that up to the multigram (or kilogram if you are lucky) scale in a non-expensive and safe manner that can be implemented in industry, well… THAT is the biggest challenge!

In this paper, Xiaohu Deng and colleagues at Johnson & Johnson Pharmaceutical Research and Development in San Diego, describe the ‘ideal synthesis’ of a CCK1/CCK2 dual receptor antagonist on a multi-gram scale, without protecting groups and in an environmentally friendly way.

This is an example of how academic research is translated into industrial applications.

Both the referees and the editorial office found this paper very interesting and selected it as a HOT article, which means it is free to access for 4 weeks! Download it now.

Protecting-group-free synthesis of a dual CCK1/CCK2 receptor antagonist
Jing Liu, Xiaohu Deng, Anne E. Fitzgerald, Zachary S. Sales, Hariharan Venkatesan and Neelakandha S. Mani
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB01004A, Paper

Aminoglycoside antibiotics are widely used in hospitals to treat serious and life-threatening infections. Because of their widespread use, bacterial resistance is becoming more of a problem and the search for aminoglycosides which are not affected grows ever more urgent.

Sylvie Garneau-Tsodikova, Micha Fridman and their colleagues from University of Michigan and Tel Aviv University have investigated the effect of 6′- and 6′′′-N-acylation of aminoglycosides on their ability to avoid bacterial resistance while retaining their antibiotic effect. The best compounds synthesised retained their full antibiotic effect against resistant strains whilst that of their parent compound was compromised. The authors have thus opened up a new route for aminoglycoside modification and demonstrated effective lead compounds for further development—the evolutionary struggle between man and pathogenic bacteria continues.

The referees enjoyed this paper and so did we, so read this HOT article in OBC today! It is free to access until 1st April 2011.

Assessment of 6′- and 6′′′-N-acylation of aminoglycosides as a strategy to overcome bacterial resistance
Pazit Shaul, Keith D. Green, Roi Rutenberg, Maria Kramer, Yifat Berkov-Zrihen, Elinor Breiner-Goldstein, Sylvie Garneau-Tsodikova and Micha Fridman
Org. Biomol. Chem., 2011, Advance Article

DOI: 10.1039/C0OB01133A, Paper