Pushing the frontiers

Chemists are under increasing pressure to be more productive, especially in drug discovery programmes. Samantha Dunnage, chemistry product specialist at Asynt, considers a replacement for traditional oil baths.

There have been many advances in the equipment and techniques utilised at the forefront of chemistry research over the past 10 years, some of which have made significant and permanent improvements to the daily workflow of the chemistry laboratory. Advanced technologies such as high throughput automated synthesis and combinatorial chemistry led the way, but now these are used only by a few specialist groups. Improvements then focused on more pertinent compound libraries, but the demand to increase productivity was higher than ever; there was a huge gulf between combinatorial chemistry and one-at-a-time bench chemistry, with very little sufficiently able to fill the gap.

microwave synthesis

Technology has not stopped here; microwave synthesis has now been accepted as a simple and very rapid tool for improving the productivity of the chemist, and in some chemistry laboratories it has now taken over from parallel synthesis as the preferred high throughput approach.

But even in the laboratory equipped with the latest parallel and microwave technologies, one of the oldest synthesis tools is still in use by chemists every day: the oil bath. A metal or glass dish containing silicon or mineral oil is used in conjunction with a hotplate stirrer to heat and stir round-bottomed flasks containing a mixture of reagents and solvents. Many issues that arise with oil baths make them unfriendly, messy and sometimes hazardous to use.

improved environment

UK-based Asynt is committed to developing and offering new technologies for chemists, with an emphasis on products that can improve the working environment. The company saw that a new reaction system would be safer and friendlier than an oil bath; cheap and simple to use.

The DrySyn product range, launched in March 2004 with the Classic, was born out of discussions with chemists about their essential needs, as well as what would make a desirable product for them as individuals.

The hard anodized aluminium base and inserts are highly engineered to fit on standard hotplate stirrers and accept standard round-bottomed flasks of 50, 100, 250, 500 and 1000ml capacities. Since its launch, the flexibility and safety of the Classic has led to its adoption by pharmaceutical companies, contract research organisations and universities. To further diminish any need for oil baths in the laboratory, a version capable of handling 2000 and 3000ml flasks - the DrySyn MAXI - was developed following requests from scientists.

system conditions

The DrySyn Classic and MAXI units have indeed made an impact on the productivity of chemists. Due to the fire hazards associated with oil at elevated temperatures, some companies have banned reactions that require overnight heating. These reactions can now be performed in much safer conditions, as the DrySyn performs in a very similar way to the oil baths (see figure 1), allowing the chemist to change to the new technology with no performance compromise.

Leading drug discovery company Tripos Discovery Research has purchased multiples of both the Classic and MAXI baths for its state-of-the-art laboratories in southwest UK. 'Our existing DrySyn units have proved themselves with their ability to outperform the heat conducting properties of oil baths,' said Dr Peter Mundell, group leader, scale-up chemistry.

'They pose a far lower fire risk, and their use makes the clean-up of glassware far easier as there is no residual oil contamination on the outside of the flasks.' As mentioned earlier, parallel synthesis apparatus has improved the efficiency of many chemistry departments in the pharmaceutical industry, but there is still a gap between oil bath heating and these devices.

'The oil bath at smaller scales can be utilised as a basic parallel reactor, simply by placing two or three flasks or tubes in situ - a simple technique favoured by academic research groups. However, this makes it difficult to ensure efficient stirring, as well as good visibility.'

fire hazard

It was with this in mind that the DrySyn MULTI concept was developed in conjunction with the Department of Chemistry at Cambridge University. 'In the university, we have used oil baths to heat reactions on stirrer hotplates, but these are a fire hazard as well as being messy and leaving residues that can contaminate other glassware when being washed up,' commented technical officer Dr Richard Turner.

'Although other metal bath type heating options were available, they lacked flexibility and were heavy,' he added. 'Asynt collaborated with us to design DrySyn MULTI, which offers us the freedom to heat different sizes of flask and tube at the same time, and has a convenient place for a thermocouple for controlled heating.'

Martyn Fordham, Asynt's product director, explained: 'We wanted the DrySyn MULTI to be a versatile, low cost product for small scale synthesis. The design incorporates a flat plate that sits on the hotplate stirrer and a range of flask inserts for 25ml to 100ml. For even smaller scale reactions, we devised an insert that will take four reaction vials. The MULTI enables the chemist to do one, two or three reactions in round-bottomed flasks, or up to 12 in vials.'

The multiple reaction component of the DrySyn range has also been extended, with the MULTI-M able to incorporate up to three 10-250ml round bottom flasks. By keeping the flasks within the confines of the hotplate, with both MULTI and MULTI-M even viscose solutions can be evenly stirred and heated. Single reactions can be placed in a central position on the MULTI-M to maximise this heating and stirring efficiency.

Furthermore, the specially designed clamping systems can support all three flasks separately to the hotplate, which allows rapid removal of the heat source from the reactions if required. This feature also makes movement of the flasks between DrySyn units at different temperatures, and an ice bath, for instance,very easy.

Asynt is committed to the ongoing development of a range of products that make life easier for the chemist. Additions to the DrySyn range are currently under development, as well as products to improve other areas of the chemist's day-to-day routine.

hydrogenations

Asynt is also in partnership with chemistry technology companies, such as PharmaCore, to offer a fast, competitive and reliable route to outsource tricky or time-consuming scaffolds essential to drug discovery.

One of the most exciting new developments is the H-Cube from Asynt partner Thales Nanotechnology. It is a simple-to-use system for performing hydrogenations safely in the standard lab fume cupboard, and generates hydrogen internally through the electrolysis of water, thereby eliminating the danger of using hydrogen cylinders.

Through a novel CatCart system it also negates the need for pyrophoric catalyst filtration.

'Safety has often been an overlooked luxury in the chemistry laboratory, but we are aiming to change this from the basics up,' stressed Fordham.