Since the first use of microwaves in chemistry was described in 1986 the field has undergone constant and rapid growth with over 4000 publications citing their use to speed up and enable difficult chemical reactions - 700 of these were published in 2006. This growth was exemplified at the 5th International Microwaves in Chemistry Conference, held at the UK's Imperial College last week where the adoption of the technique was shown to have grown from small molecule synthesis applications, to high-throughput synthesis laboratories, peptide synthesis, protein digestion and proteomics. "The whole area of microwaves is moving very quickly and is really transforming the world of science in many different ways - the field started off being described as microwave chemistry but is now being known as microwave enhanced science," said Dr Mike Collins, CEO of microwave instrument company CEM who sponsored the event. Numerous examples were shown where the use of microwave heating has enabled hard to do reactions or led to increases in efficiency by dramatically shortening reaction times. Dr David Smith from Sanofi Aventis presented a poster showing the use of microwaves to enable the difficult multiple isotopic labelling of an antimalarial agent, Ferroquine (SSR97193), currently in Phase I trials. Isotopic labelling of drugs allows them and their metabolites to be tracked more easily through disease models to help the researchers understand the drugs mechanism of action and their pharmacokinetic profile. Microwave heating has also been found to be beneficial for transition metal catalysed reactions where reaction rates can be increased by up to 100-fold. Dr Mark Bagley, of the University of Cardiff, told LabTechnologist.com that this is because the microwaves superheat the metals to far higher temperatures than the bulk solution. Bagley's group is currently using microwave and flow-chemistry techniques to enable his group's research into potential heterocyclic drugs for Werner's syndrome - a rare premature aging disease where cells go into a state of senescence earlier than they should. The group have had some success in this area, but Bagley said that: "aging research takes a long time". UK-based specialty chemical company, Reaxa, presented results of how the company's EnCat range of encapsulated transition metal catalysts provides safer and cleaner catalytic reactions with shorter reaction times. "We feel that the inherent safety of the microwave instruments coupled with the safety aspects of the EnCat catalysts allows researchers to carry out reactions that they wouldn't normally be allowed to perform due to health and safety concerns," said Dr Mike Pitts, R&D Project Leader at Reaxa. He continued to explain that because the EnCat catalysts do not leach there is no problem with metal plating the surface of the tubes that can lead to arcing in the microwave or the build up of toxic fumes if working with osmium catalysts. "The EnCat system also offers a beautiful way to do catalytic flow chemistry in a microwave - a subject we have been collaborating on with Professor Steve Ley of Cambridge University," continued Dr Pitts. The uptake of the technique by pharmaceutical companies was highlighted by Dr Brian Shook, a member of Johnson & Johnson's high-throughput (HT) laboratories where the use of automation and microwave reactors allows the company's chemists to produce over 5,000 molecules a year for use in HT screening programs. "My job is to make compounds quickly and efficiently and microwaves definitely help me to do my job better," he said. He continued by saying that the use of microwaves had enabled him to run 30 reactions in two days rather than two months. The technology is no longer just being used in organic chemistry applications but is making rapid inroads into the bioscience sectors. This new emerging area of microwaves in bioscience was highlighted by Jonathan Collins, manager of the Bioscience Division at CEM and Nicholas Leadbeater, of the University of Connecticut, US, in a paper published in the latest edition of Organic and Bimolecular Chemistry. The introduction of CEM's peptide synthesiser, the Liberty, has helped Professor Ben Davis, of the University of Oxford, in synthetically manipulating proteins with the aim of forming synthetic antibodies. CEM have now sold over 100 of these peptide synthesisers in less than two years, and they are now being used in many well-known research facilities and companies. "We have seen a great acceptance of microwave systems in the peptide synthesis community, because they give biochemists the ability to perform new syntheses and do things that simply weren't possible using conventional methods," said Dr Collins. The instruments have been found to allow the synthesis of difficult peptides that cannot be made using conventional methods. This has been ascribed to the polarizing effect of the microwaves that causes the peptides to straighten out; reducing the back folding that can hinder many supported peptide syntheses. Dr Jennie Lill, of Genentech's microchemistry and proteomics laboratory in San Francisco, US, has been using microwaves to dramatically speed up the enzymatic deglycosylation of proteins. The researchers working with Dr Lill use mass spectrometry techniques to analyse biological molecules being designed as therapeutics. These can have molecular weights of up to 150 kDalton and are often heavily glycosylated making the task of measuring the molecular weight of the intact protein very complicated as various different sugar groups can be attached. Removing the various sugar groups allows accurate molecular weight analysis to be conducted, but this can take as long as two days using conventional techniques and causes a huge bottleneck in laboratories. "We see a significant decrease in incubation time using microwave assisted deglycosylation," she said. She continued by saying that these difficult-to-do N-linked deglycosylations can be conducted in less than two hours with microwave assisted techniques using the same PNGase F enzyme. For example, the complete deglycosylation of Genentech's blockbuster colorectal cancer antibody Avastin (bevacizumab) can be conducted in 10 minutes using microwave heating techniques whereas the reaction is still not completed after an hour using conventional heating at the same temperature. While intact mass measurements are useful, sequence information is also required and microwave techniques can also help speed-up these processes. Using microwave techniques digestion times for many proteins can be reduced from 18 hours to about 30 minutes with the identification of at least as many peptide fragments. CEM supply the Discover enzymatic digestion system to assist in microwave-assisted proteomic sample preparation as well as the Discover protein hydrolysis system to accurately control acid hydrolysis experiments. Furthermore, CEM recently announced a new automated extraction system, the ExplorerQ, which can shorten extraction times of pharmaceutical and environmental samples from solids. The system allows sample extractions into a minimum amount of solvent in minutes rather than hours.
Microwave instruments have been speeding up chemical reactions for over 20 years and the uptake of the technology is now spreading into the bioscience sector as well.