Cold‐spray ionization mass spectrometry: principle and applications

Abstract A direct solution analysis method, cold‐spray ionization (CSI) mass spectrometry (MS), a variant of electrospray (ESI) MS operating at low temperature (ca −80 to 10 °C), allows the facile and precise characterization of labile organic species, especially those in which non‐covalent bonding interactions are prominent. We applied this method to investigations of the solution structures of many labile organic species, including unstable reagents and reaction intermediates, asymmetric catalysts, supramolecules and even primary biomolecules. Remarkable analytical results were obtained for highly ordered supramolecules using the CSI method. Whereas conventional ESI is not applicable to these compounds because of their instability to heat and/or air, CSI affords multiply charged molecular ions with many solvent molecules attached. Investigation of the constitution of Grignard reagents in solution is extremely challenging, but CSI‐MS allowed us to identify one of the key structures in THF solution. Recently, this method was adopted for investigations of the solution structures of primary biomolecules such as nucleosides, amino acids, sugars and lipids, revealing singly charged Na + adducts of large clusters (chain structures), presumably linked by non‐covalent interactions, including hydrogen bonding and/or hydrophobic interactions. The principle of the CSI method and applications of the method to a wide variety of labile organic species and primary biomolecules in solution are described. Copyright © 2003 John Wiley & Sons, Ltd.