, or Cs ϩ therefore represent a new type of cluster ion that is homochiral in its internal subunits, which then assemble in a random fashion to form octamers. We tentatively interpret the homochirality of these tetramers as a consequence of assembly of the serine molecules around a central metal ion. The data provide additional evidence that the neutral serine octamer is homochiral and is readily cationized by smaller ions. (J Am Soc Mass Spectrom 2007, 18, 856 -868) © 2007 American Society for Mass Spectrometry C ations of the alkali metals, especially Na ϩ and K ϩ , are involved in a wide variety of biological processes. To take just one example, they participate in the stabilization of noncovalently bound complexes of biological macromolecules in living organisms. In particular, telomeric DNA found at the ends of chromosomes is stabilized by forming multistrand complexes, known as G-quadruplexes, which are held together by hydrogen bonds and further stabilized by the incorporation of alkali metal cations into cavities in their structures [1][2][3]. Mass spectrometry [1], nuclear magnetic resonance, X-ray crystallography and other spectroscopic techniques have shown that small biomolecules can also form relatively stable clusters with alkali metal cations. Examples include nucleobases [4 -6] and nucleosides (as well as their derivatives) [7][8][9], and amino acids [10,11]. A particular feature of alkali metal adducts of small molecular clusters is that they often have a net positive charge and can be characterized by mass spectrometry, a technology that has proven to be key in many studies of clusters [11][12][13][14][15][16][17][18][19].Electrospray ionization (ESI) [20,21] is a versatile ionization technique, which allows biological macromolecules, fragile noncovalently bound complexes [22][23][24][25][26], and other fragile nonvolatile species to be easily transferred from solution into the gas-phase, where mass spectral data can be obtained on the resulting ions. Although the possibility exists of conformational rearrangement [27,28] and other structural changes during the ESI process, there is overwhelming evidence that electrospray ionization is successful in the characterization of solution-phase species via a study of the corresponding gas-phase ions [24,26]. Spray ionization methods derived from the original ESI method include sonic spray ionization (SSI) [29,30] and cold spray ionization (CSI) [31,32]. Recently, electrosonic spray ionization (ESSI) [33,34], a combination of ESI and SSI, was introduced. This particular spray ionization method is very gentle, yet readily yields fully desolvated ions [33,34]. The variant methods SSI, CSI, and ESSI are all believed to provide gentler ionization than normal electrospray, allowing labile species that exist in solution to survive the ionization process as well as being applicable to nonvolatile analytes.The droplet evaporation process in the gentle variant methods on ESI can lead to even more aggregation than occurs in ESI itself. This tendency has been fo...