Organic & Biomolecular Chemistry Blog

This latest contribution to the debate over the origin of catalysis in the chorismate mutase enzyme may bring an end to the controversy surrounding the nature of its transition state.

Adrian Mulholland and collaborators at the University of Bristol have used quantum and molecular mechanics to model the rearrangement of chorismate to prephenate in Bacillus subtilis chorismate mutase and aqueous solution. The chorismate mutase enzyme is a favourite model for theories of biological catalysis, but there is still disagreement on exactly how it occurs.

The team found that a slightly different reaction path was followed in each environment and that there were differences in the transition state structures between water and the enzyme.  A significantly more stable transition state was formed in the enzyme. These results are in opposition to previously published work which suggested that catalysis in the enzyme does not involve  transition state stabilisation at all, but rather is due to the formation of a reactive conformation of the substrate.

The referees were impressed with the careful and thorough nature of this study – read the full article online here, it’s free until the end of February.

Analysis of chorismate mutase catalysis by QM/MM modelling of enzyme-catalysed and uncatalysed reactions
Frederik Claeyssens, Kara E. Ranaghan, Narin Lawan, Stephen J. Macrae, Frederick R. Manby, Jeremy N. Harvey and Adrian J. Mulholland
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB00691B

This HOT paper by Graham Hutchings and co-workers describes a cautionary tale of solubility, as the group discovered a systematic error in HPLC measurements of the enantiomeric excess of N-arene-sulfonyl-2-phenylaziridines.

They showed that the heterogeneous or homogeneous copper-catalysed synthesis of N-arene-sulfonyl-2-phenlaziridines mainly yields the R enantiomer.  However previous reports significantly over-estimate the percentage enantiomeric excess when hexane was used as the HPLC injection solvent, due to the formation of an insoluble racemic phase.

The group has improved their analytical procedure to afford the correct value, but advise that previous reports on the
enantioselectivity of copper-catalysed aziridination reactions ‘should be regarded with caution if the analytical
procedure involved HPLC’.

Both reviewers thought this well-presented study is of importance to the field.  Download it today – it’s now free to access until 8th February.

On the enantioselectivity of aziridination of styrene catalysed by copper triflate and copper-exchanged zeolite Y: consequences of the phase behaviour of enantiomeric mixtures of N-arene-sulfonyl-2-phenylaziridines

Laura Jeffs, Damien Arquier, Benson Kariuki, Donald Bethell, Philip C. Bulman Page and Graham J. Hutchings

Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB00724B, Paper

Poul Nielsen and his group at University of Southern Denmark describe the synthesis of new double-headed nucleosides, using the CuAAC reaction, and their influence on the stability of the hybridization of oligonucleotides.

In this HOT paper they describe a new type of nucleosides that are able to stabilize three-way junctions. If you want to find out more about these interesting stabilising contacts download the article, which is free to access until the 8th February.

The synthesis of double-headed nucleosides by the CuAAC reaction and their effect in secondary nucleic acid structures
Anna S. Jørgensen, Khalil I. Shaikh, Gerald Enderlin, Elise Ivarsen, Surender Kumar and Poul Nielsen
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB00438C

To give you a better overview on Nielsen’s previous research, we have outlined below a collection of their latest OBC published papers. Enjoy!

Stabilisation of nucleic acid secondary structures by oligonucleotides with an additional nucleobase; synthesis and incorporation of 2′-deoxy-2′-C-(2-(thymine-1-yl)ethyl)uridine
Søren Ljungberg Pedersen and Poul Nielsen
Org. Biomol. Chem., 2005, 3, 3570-3575
DOI: 10.1039/B510167K

Synthesis and modelling of DNA junction and minor groove zipper motifs incorporating the double-headed nucleoside 5′(S)–C-(thymine-1-ylmethyl)thymidine
Mikkel S. Christensen, Charlotte M. Madsen and Poul Nielsen
Org. Biomol. Chem., 2007, 5, 1586-1594
DOI: 10.1039/B700852J

Nucleic acid secondary structures containing the double-headed nucleoside 5′(S)-C-(2-(thymin-1-yl)ethyl)thymidine
Charlotte Andersen, Pawan K. Sharma, Mikkel S. Christensen, Signe I. Steffansen, Charlotte M. Madsen and Poul Nielsen
Org. Biomol. Chem., 2008, 6, 3983-3988
DOI: 10.1039/B810930C

Adrien Quintard and Alexandre Alexakis from the University of Geneva report a systematic study on the application and scope of the 1,2-sulfone rearrangement and notably on its asymmetric variant. 

A wide variety of nucleophiles can be used to yield highly functionalised substrates, with some demonstrating excellent enantioselectivities of up to 94% ee.  This 1,2-sulfone rearrangement constitutes an alternative to the use of expensive 1,1-bis(phenylsulfonyl)ethene and leads to a formal alkylation of the nucleophile.

Both reviewers thought this HOT article would be of very wide interest in the organic community and it is now free to access until 8th February.

1,2-Sulfone rearrangement in organocatalytic reactions
Adrien Quintard and Alexandre Alexakis
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB00818D

Carl Schiesser takes us through the evolution of Free Radical Chemistry in this very original and well written paper that highlights results from the Beckwith “golden era”.
Join us in this trip from the “Dark Ages” of Free Radical Chemistry to the Post-Renaissance period.  The paper will be free to access until 4th February.

In the paper, they determine the rate constant data and Arrhenius parameters for a series of substituted hexenyl radicals of differing electronic and steric demand.

This paper will be included in the special issue on ‘Free Radical Chemistry’ in memory of Athel Beckwith that will be published in Spring. Keep an eye on it.

Treasures from the Free Radical Renaissance Period – Miscellaneous hexenyl radical kinetic data
Athelstan L. J. Beckwith and Carl H. Schiesser
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB00708K, Paper

Inhibition of angiotensin converting enzyme (ACE) is generally used as one of the methods for the treatment of hypertension. ‘Oxidative stress’ is another disease state caused by an imbalance in the production of oxidants and antioxidants. Hypertension and oxidative stress may be interdependent. Therefore, ACE inhibitors having antioxidant properties are considered beneficial for the treatment of hypertension.

Bhaskar J. Bhuyan and Govindasamy Mugesh at the Indian Institute of Science in Bangalore, India, synthesise in this paper a number of selenium analogues of captopril, an ACE inhibitor used as an antihypertensive drug. These analogues not only inhibit ACE activity but also effectively scavenge peroxynitrite, a strong oxidant found in vivo.

Read this paper which is free to access until the 4th February. The referees strongly recommended it and the editorial office as well.

Synthesis, characterization and antioxidant activity of angiotensin converting enzyme inhibitors Bhaskar J. Bhuyan and Govindasamy Mugesh
 Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB00823K, Paper

Bruce A. Armitage and his team at Carnegie Mellon University in Pittsburgh, USA, create a new family of blue fluoromodules with low nanomolar Kds and high quantum yields.
These fluoromodules provide a new technology for multicolour fluorescent labelling and cellular imaging.

This is a very interesting paper that has been rated as very significant by all the referees.

You don’t want to miss this one! Read it now – it is free to access until the 4th February.

Blue fluorescent dye-protein complexes based on fluorogenic cyanine dyes and single chain antibody fragments
Kimberly J. Zanotti, Gloria L. Silva, Yehuda Creeger, Kelly L. Robertson, Alan S. Waggoner, Peter B. Berget and Bruce A. Armitage
Org. Biomol. Chem., 2011
DOI: 10.1039/C0OB00444H