Recent results in laser-solid interactions indicate that there is a convenient way to propel large molecules into the gas phase with little or no degradation. This particularly exciting new method, matrix-assisted laser desorption ionization (MALDI), has enormously expanded the mass range for the spectroscopy of high molecular weight biomolecules. No adequate theory is yet available to explain the entire method, or even parts of it like co-crystallization or ion formation. The proposal plans to study the chemistry and physics of the mechanisms that produce the sample crystals, energize, eject, and ionize the molecules from condensed molecular samples with emphasis on the MALDI experiments on proteins and nucleic acids. Two limits of the ejection process will be explored: the hydrodynamic (HD) limit and the molecular dynamic (MD) limit. The two descriptions complement each other in terms of time scales (<200 ps for MD vs. 1 ns to 100 ns for HD) and accessible information (molecular vs. bulk properties). Large biomolecules are hard or impossible to evaporate since they tend to decompose before reaching high-enoughtemperature. The most accurate spectroscopic methods, however, rely on gas phase molecules. A recently discovered phenomenon, called matrix-assisted laser desorption/ionization (MALDI), gets around this problem by embedding the large molecules into an easy-to-evaporate matrix that can be excited by pulsed laser radiation. The MALDI method has provided unprecedented accuracy in the molecular mass determination of large proteins and other biomolecules. Despite the great benefits of this method, understanding of the underlying processes is lagging behind. The proposal plans to explore the chemistry and physics of the mechanisms that produce the sample crystals, energize, eject, and ionize the molecules from condensed molecular samples with emphasis on the MALDI experiments on proteins and nucleic acids. Improved understanding of the basic phenomena involved will help to extend the capabilities of MALDI for a larger group of important biomolecules.
