Archive for the ‘Hot articles’ Category

HOT: ultra-sensitive fluorescence quenching to detect molecular recognition events

Achieving sensitive signal detection in fluorescence-based assays often involves chemically pre-amplifying the signal to detectable levels.   There are currently several methods of achieving amplification, but here Andrei Kutateladze and colleagues at the University of Denver come up with a concept different from previous methods based on photoamplified fluorescence quenching.

General concept for the amplified unmasking of benzophenone resulting in fluorescence quenching

They are able to detect molecular recognition events in the biotin-avidin system through the autocatalytic photo-unmasking of benzophenone – which acts as both the amplification chain carrier and the quencher for the reporter fluorophore – achieving attomolar detection limits with a relatively cheap CCD camera.  They even demonstrate the possibility of imaging the binding assay with an ordinary mobile phone camera, showing that sensitive analysis can be carried out when expensive state-of-the-art equipment is not available.

To read more, download the article – it’s free to access for the next four weeks:

Photochemically amplified detection of molecular recognition events: an ultra-sensitive fluorescence turn-off binding assay
Tiffany P. Gustafson, Greg A. Metzel and Andrei G. Kutateladze
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C1OB05289F

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

HOT: multivalent strategies for RGD peptide-integrin binding

Integrins play important roles in cell adhesion and signalling, and crucially are over-expressed in certain cancer cells.  The tripeptide Arg-Gly-Asp (RGD) is known to bind to integrins, and understanding exactly how they bind is obviously of fundamental importance for the development of structures with higher integrin affinities for possible therapeutic applications.

Here, Daniel Welsh and David K. Smith (University of York) investigate different ways in which the peptide ligands can be organised for multivalent binding to integrins. Although integrins only posses a single binding site they often grouped together in cell membranes, so mutlivalent binding to multiple integrins is possible.  They investigate both dendritic (covalent) and self-assembly (non-covalent) strategies, finding both can be used in similar ways to enhance the binding of RGD peptides to integrins, but that the self-assembly approach appears to give rise to slightly higher affinity integrin binding.

To find out more download this article – it’s free for the next four weeks:

Comparing dendritic and self-assembly strategies to multivalency—RGD peptide–integrin interactions
Daniel J. Welsh and David K. Smith
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C1OB05241A

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

HOT: sweet but not sickly – non-cytotoxic sugar amino acid-containing antimicrobial agents

As bacteria continue to resist our efforts to eradicate them, the development of new antibiotics with alternative modes of action are required to augment existing treatments.  Cationic antimicrobial peptides (CAPs) show potential, but are often too cytotoxic to be developed as new antibiotics.  One way to get around the cytotoxic mechanisms is to attach agents to carriers, such as gold nanoparticles which are non-toxic to cells and biocompatible.

In this HOT paper Tushar Kanti Chakraborty and colleagues from the Central Drug Research Institute, India, have synthesised some novel sugar amino acid-containing cyclic cationic peptides and attach them to gold nanoparticles to study their therapeutic effects. The preliminary studies found that the sugar amino acid-containing CAPs retained their antimicrobial activity on conjugation with the nanoparticles, but with significantly reduced cytotoxic effects.

Download the article to discover more about the study and the potential mechanism for these CAPs – it’s free to access for four weeks:

Towards the synthesis of sugar amino acid containing antimicrobial noncytotoxic CAP conjugates with gold nanoparticles and a mechanistic study of cell disruption
Sudip Pal, Kalyan Mitra, Sarfuddin Azmi, Jimut Kanti Ghosh and Tushar Kanti Chakraborty
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C1OB05338H

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

HOT: Monitoring intracellular copper levels in living cells

Copper is an essential trace element in the physiology of living organisms as many critical proteins and enzymes contain copper in their active sites or/and require copper for their activities.
Disruption of copper levels in cells can cause diseases such as Menkes syndrome, Wilson’s disease, amyotrophic lateral sclerosis and Alzheimer’s. Therefore, the quantitative detection of intracellular copper could help with the understanding of its complex physiological and pathological roles.

Unlike other trace metals such as zinc, iron, chromium and mercury, which can be successfully detected with rhodamine-based fluorescence probes, the detection of copper has proven to be more challenging and the development of satisfactory fluorescent probes needs addressing.

Bao-Xiang Zhao, Jun-Ying Miao and colleagues at Shandong University in China have now developed a rhodamine chromene-based fluorescence probe to monitor the intracellular levels of copper in living cells. The probe switches to a highly fluorescent complex upon coordination with copper under physiological conditions in a very sensitive and selective manner and facilitates the naked-eye detection of the metal.

If you want to learn more about this satisfactory fluorescent probe I invite you to download this paper that is free to access until 15th June.

Synthesis, crystal structure and living cell imaging of a Cu2+-specific molecular probe
Wei-Yong Liu, Hai-Ying Li, Bao-Xiang Zhao and Jun-Ying Miao
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C1OB05358B

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

HOT: One electron oxidation of substituted ferrocenes

How can the structure of short-lived N-oxyl radicals influence its electron transfer (ET) properties?

Osvaldo Lanzalunga and his team at Sapienza Universita di Roma and Istituto CNR di Metodologie Chimiche (IMC-CNR) provide some answers to this question in this OBC HOT paper.

They study the kinetics of the one electron oxidation of substituted ferrocenes by a series of N-oxyl radicals in acetonitrile and determine self-exchange reorganization energy values.
They conclude by saying that ‘even small modifications of the structure of the N-oxyl radicals lead to signifiant variation of the self-exchange reorganization energy values.’

If you want to read more about these results, you can download the paper for free until 8th June.

This paper is part of the Free Radical collection of papers in memory of Athel Beckwith, which will be published at the end of May. Watch this space.

One-electron oxidation of ferrocenes by short-lived N-oxyl radicals. The role of structural effects on the intrinsic electron transfer reactivities
Enrico Baciocchi, Massimo Bietti, Claudio D’Alfonso, Osvaldo Lanzalunga, Andrea Lapi and Michela Salamone
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB01257B

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

HOT: Radical route to lactams

Lactams are often used as building blocks for antibiotics, such as penicillin. Now Hiroshi Matsubara, Ilhyong Ryu and colleagues have investigated an exciting radical route to produce them.

They show that acyl radicals can react as electrophiles in ionic type addition reactions with amines, which leads to cyclisation forming a series of lactams. Depending on the N-substituent (good or not good leaving group) reaction occurs via rare 1,4-H shift or via a formal homolytic substitution at nitrogen leading to interesting new compounds.

Download the paper now to read more about the synthetic scope and theoretical findings. It is free to access until 25th May.   

This article will be included in the OBC special issue in memory of Athel Beckwith: Free Radical Chemistry. Coming soon

Radical carbonylation of ω-alkynylamines leading to α-methylene lactams. Synthetic scope and the mechanistic insights
Ilhyong Ryu, Takahide Fukuyama, Mami Tojino, Yoshitaka Uenoyama, Yuka Yonamine, Nozomi Terasoma and Hiroshi Matsubara
Org. Biomol. Chem., 2011, 9, 3780-3786
DOI: 10.1039/C1OB05145H

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

HOT: Switch on the rotaxane!

Rotaxanes are mechanically interlocked molecules with interesting physical and chemical properties. They have attracted much attention due to their potential applications in molecular electronics, smart materials and molecular machines.

In this HOT paper, Da-Hui Qu, He Tian and their research group at East China University of Science & Technology in Shanghai, synthesise a multi-state [2]rotaxane based on a crown ether. They introduce a dithienylethene (DTE) photochromic functional group that can be switched by pH, light or the combination of pH and light. This photochromic unit is responsible of the multi-mode alteration of intercomponent interactions such as energy transfer, electron transfer and charge transfer interactions.

This multi-state molecular shuttle has potential to construct multi-level molecular machines.

You can now read this article, which is free to download until 25th May, here.

The referees and the editorial office found it very interesting. We hope you like it too.

Altering intercomponent interactions in a photochromic multi-state [2]rotaxane
Hui Zhang, Xin-Xin Kou, Qiong Zhang, Da-Hui Qu and He Tian
Org. Biomol. Chem., 2011
DOI: 10.1039/C1OB05307H

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

HOT article: upping the TEMPO-H

The stable radical TEMPO is an an important molecule for organic catalysis, and its protonated cousin TEMPO-H is an excellent chemical source of hydrogen.  However, Jason Masuda and Jason Clyburne (Saint Mary’s University, Canada) were concerned that, due to the current synthetic route, water present in TEMPO-H could lead to unwanted side reactions.

In this HOT paper they overcome this problem by reporting the first anhydrous route to TEMPO-H (2,2,6,6-tetramethylpiperidin-1-ol), by treating the sodium salt of TEMPO with triethylamine hydrochloride.  They show that the anhydrous form is not only more stable during synthesis, but that it has a different structure and reactivity patterns as well.  They tested their anhydrous compound against several molecules with low valence carbon centres such as carbenes and ketenes, demonstrating the use of the anhydrous form in avoiding side reactions and creating different complex structures.

Preparation of anhydrous TEMPO-H

You can read the full details of the synthesis and characterisation for free until 14th May:

Anhydrous TEMPO-H: reactions of a good hydrogen atom donor with low-valent carbon centres
Nick A. Giffin, Miller Makramalla, Arthur D. Hendsbee, Katherine N. Robertson, Cody Sherren, Cory C. Pye, Jason D. Masuda and Jason A. C. Clyburne
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB00999G, Paper

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

HOT: Novel efficient synthesis of functionalised naphthoquinones

Naphthoquinone derivatives have important pharmacological properties. They have been explored for their anti-inflammatory, antifungal and antitumor biological activities amongst many others. Therefore, efficient syntheses of naphthoquinines are of great interest.

In this paper, Jian Wang and his team at the National University of Singapore, have developed a new catalytic synthetic method for the preparation of chiral naphthoquinones with a novel chiral thiourea catalyst. They achieve excellent yields (94-99%) and excellent enantioselectivities (90-98% ee)

Read more about this new and very efficient synthesis in this HOT paper which is free to access until 14th May.

Enantioselective organocatalytic Michael-hemiketalization catalyzed by a trans-bifunctional indane thiourea catalyst
Yaojun Gao, Qiao Ren, Swee-Meng Ang and Jian Wang
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C1OB05404J

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

HOT: Effect of substituents on the stabilities of radicals

The effect of substituents on the thermodynamic stabilities of trisubstituted carbon-centered radicals is an interesting topic that has received limited attention in literature until now.

Now, Leo Radom and collaborators in Australia and Switzerland present in this paper a thorough computational study, which correlates with experimental data, of the stability of a very large series of multiply-substituted carbon-centered radicals. They look at the stabilization and interaction energies and the deviations from additivity of RSEs.

If you want to learn about the 14 conclusions they reach in this HOT article, download it now. It is free to access until 5th May.

This article will be included in the OBC special issue in memory of Athel Beckwith: Free Radical Chemistry. Coming soon.

Effect of substituents on the stabilities of multiply-substituted carbon-centered radicals
Ambili S. Menon, David J. Henry, Thomas Bally and Leo Radom
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C1OB05196B

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)