Organic & Biomolecular Chemistry Blog

Although the presence of ozone and NO_x gases (i.e. NO^. and NO₂^.) are often linked to an increase in respiratory conditions such as asthma, the mechanism by which these pollutants cause respiratory distress is still not clear. Interestingly, the highly reactive NO₃^. (formed in the atmosphere at night by reaction of O₃ and NO₂^.) has been somewhat overlooked as a possible respiratory irritant despite numerous studies on its role in the atmosphere.

In this HOT paper Uta Wille and colleagues at the University of Melbourne follow up a previous study published in Chem. Comm. which identified the products of the reaction of the NO₃ radical with amino acids.  Now, they have simulated the exposure of proteins present at the surface of the respiratory tract to a number of environmental pollutants, determining clear reaction pathways resulting in aromatic ring nitration of the amino acids studied.  They note that nitrated aromatic amino acids are often observed in a wide range of inflammatory-immune responses such as asthma and cystic fibrosis, leading them to suggest that the NO₃ radical could actually be the real culprit in certain pollution-related diseases.

You can read the full details of this interesting study online here (it’s free to access for the next month!).

This paper is included in the OBC special we themed issue on radical chemistry that will be published soon. Keep an eye on it!

Damage of aromatic amino acids by the atmospheric free radical oxidant NO3˙ in the presence of NO2˙, N2O4, O3 and O2
Catrin Goeschen, Natalia Wibowo, Jonathan M. White and Uta Wille
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB01186J

And the previous Chem. Comm. paper can be found here:

Can the night-time atmospheric oxidant NO3˙damage aromatic amino acids?
Duanne C. E. Sigmund and Uta Wille
Chem. Commun., 2008, 2121-2123
DOI: 10.1039/B803456G

This computational study addresses the possible isomerisation of 1,2,3-trialkylimidazolium and 1-alkylpyridium ion pairs through proton transfer.  The formation of neutral species in protic room temperature ionic liquids has been well studied, but the mechanism in other, “non-protic” species has been subject to less investigation.

Oldamur Hollóczki and László Nyulászi from Budapest University of Technology and Economics carried out the DFT study after observing that the “protic nature” of an ionic liquid depends not only on the cation, but on the cation/anion assembly.  Their investigations determined that the formation of neutral species is a viable possibility for ion pairs containing sufficiently basic anions, such as organic acids .  This, they say, means that the description of imidazolium or pyridinium based ionic liquids with basic anions as pure ionic substances is oversimplified.  The presence of trace amounts of neutral species could affect the physical properties of the ILs and any basic anions present could result in unexpected reactions in “inert” IL solvents.

Neutral species from “non-protic” N-heterocyclic ionic liquids
Oldamur Hollóczki and László Nyulászi
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C1OB00007A

Ever wanted to carry some polyions across a cell membrane? Some DNA perhaps? Well it turns out you could do with the help of a molecular octopus!

Stefan Matile et al. from the University of Geneva have undertaken a comprehensive study into the structural factors affecting the ability of “octopus” amphiphiles to carry polyions across lipid bilayers and found that the number of “tentacles” was a key factor. Their work has highlighted three key results: firstly, their approach to structure development allowed rapid production and screening of counterion libraries; secondly they have shown that activity related to tail length is also dependent on the number of tails; and finally they found that branched tails were better than their linear analogs.

These findings have a broad application across the fields of sensing, catalysis, cellular uptake and anything else that relies on transporting polyions across a membrane.

Read this HOT article now in Org. Biomol. Chem. – it is available free until 14/04/2011.

Comprehensive screening of octopus amphiphiles as DNA activators in lipid bilayers: implications on transport, sensing and cellular uptake
Javier Montenegro, Andrea Fin and Stefan Matile
Org. Biomol. Chem., 2011, Advance Article

DOI: 10.1039/C0OB00948B

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,