Chemical Communications Blog

Synthetic organic chemists have long regarded the Wittig reaction as one of the most significant methods for the creation of new C–C bonds. Now, researchers at Peking University have reported that this time-honoured reaction can be used for the modification of proteins in a bioorthogonal process.

Bioorthogonal processes represent a growing area of interest, encompassing reactions which can take place under physiological conditions. That is, the reaction must proceed at neutral pH in an aqueous solvent at ambient temperature and low concentrations, with high selectivity. Given these challenging parameters, the range of bioorthogonal processes remains limited.

The Ye group, based at the Key State Laboratory of Natural and Biomimetic Drugs, have contributed to the expansion of this fascinating area of chemistry by successfully applying the Wittig reaction to their one-pot site-selective protein modification. The first step involves the incorporation of an aldehyde at the N-terminus of a peptide chain (1). This could be achieved by the periodate oxidation of N-terminal serine or threonine residues, or by PLP (pyridoxal-5-phosphate) oxidation of N-terminal glycines. The resulting aldehyde (2), without the need for isolation or purification, could be reacted with an ylide (3) to form a wide variety of functionalised peptide products (4). Di-, penta- and hexa-peptide substrates could be functionalised in this manner, using water and t-butanol as co-solvents at room temperature.

The strength of this site-selective reaction was further demonstrated by modifying myoglobin. Crucially, this was achieved with no damage to the protein’s secondary or tertiary structure and, furthermore, Prof. Ye’s group established that myoglobin’s oxygen storage and release function was unaffected.

The functionality introduced offers the potential for further structural modification, or for use in medical imaging. With protein-based pharmaceuticals becoming widely used, greater insight into protein function and behaviour is of paramount importance. This methodology has the potential to be a valuable tool in that understanding. 

Read the ‘HOT’ Chem Comm article today:

Enabling Wittig reaction on site-specific protein modification

Ming-Jie Han, De-Cai Xiong and Xin-Shan Ye
Chem. Commun., 2012, 48, 11079-11081
DOI: 10.1039/C2CC35738K

Published on behalf of Ruth Gilligan, Chemical Communications web science writer.

Luminescence from lanthanide-based compounds is currently exploited in electroluminescent devices ranging from glucose monitoring sensors to thin-film displays. Triarylboron groups are known to greatly enhance the fluorescence or phosphorescence of transition metal complexes, but such compounds are very sensitive to oxygen quenching and are unsuitable for use as sensors under ambient conditions.  The combination of these groups with lanthanides may offer enhanced luminescence in more ambient-friendly lanthanide-based materials.

The Wang group from Queen’s University, Canada have synthesised the first examples of triarylboron functionalized Tb(III) and Eu(III) compounds, and have shown that the BMes₂ group is extremely effective at activating lanthanide emissions.  The new compounds have been tested as sensors, showing that such triarylboron functionalized lanthanides may be promising new CN^– and F^– anion sensors.

To find out more, download this HOT article now (free to access until the 5th of December 2012).

Selective activation of lanthanide luminescence with triarylboron-functionalized ligands and visual fluoride indicators

Maria Varlan, Barry A. Blight and Suning Wang

Researchers from the University of British Columbia have developed a ‘head to head’ dimerisation of alkynes to provide (Z)-enynes in high yields.

The conjugated enyne products are important, both as intermediates for organic synthesis and in optoelectronics – a type of electronics that detect, source and control light. Therefore, new methods for the selective synthesis of these compounds are in demand.

Platel and Schafer have overcome regioselectivity problems often associated with alkene dimerisation.  The researchers used a readily accessible Zirconium catalyst (2) in conjunction with aniline as co-catalytic proton source.

A number of alkynes (1) were successfully dimerised to provide (Z)-enynes (3) in mostly high yields. The reaction is tolerant of a number of differentially substituted aryl compounds and also some alkyl rings.

The exclusive formation of (Z)-enynes was at odds with previously established mechanistic pathways for metal-catalysed alkyne dimerisation and led the researchers to further probe the mechanism. Complex 4 was isolated when a stoichiometric amount of aniline and complex 2 were mixed, leading the researchers to consider the validity of 4 as a catalytic intermediate. When 4 was mixed with alkyne (1) under the reaction conditions, complete conversion to (Z)-enyne (3) was observed. This result suggests that the unusual dimeric imido-bridged species is a viable intermediate in the reaction pathway.

This method represents an interesting development in catalytic and regioselective C­–C bond formation.

Read the ‘HOT’ Chem Comm article today:

Zirconium catalyzed alkyne dimerization for selective Z-enyne synthesis
Rachel H. Platel and Laurel L. Schafer
Chem. Commun., 2012, 48, 10609-10611
DOI: 10.1039/C2CC35913H