Helium droplet isolation

Gas-phase spectroscopy of neutral molecules, as opposed to ions, usually involves the use of supersonic molecular beams [1 ]. For smaller compounds this can be achieved by seeding in the inert drive gas. This limitation excludes the study of neutral nucleosides or larger compounds while even some of the bare nucleobases, such as guanine, cannot be sufficiently heated without thermal degradation. Some work with bases and base mimics has been done in seeded beams [5-10]. Larger compounds can now be vaporized successfully by pulsed laser desorption, followed by entrainment in a supersonic jet [11-14]. This experimental advance has opened up the field of study of nucleobases and nucleosides in isolation in the gas phase, especially by IR spectroscopy. The cooling in molecular beams makes this approach particularly attractive for spectroscopy. Although temperatures are not as low as in ion traps or helium droplets, molecular beams can achieve internal temperatures typically of the order of 10-20 K, which provides very useful optical resolution. 

A universal tool in establishing tautomerism is of course temperature. Techniques that are able to go to very low temperatures such as matrix isolation IR spectroscopy and studies in helium droplets and in gas expansions are essential for the study of fast tautomeric equilibria. 

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