Chemistry Publications
Document Type
Article
Publication Date
9-17-2024
Journal
Journal of the American Chemical Society
URL with Digital Object Identifier
doi: 10.1021/jacs.4c05760
Abstract
Electrospray ionization (ESI) of serine (Ser) solution generates Ser8H+ as an abundant magic number cluster. ESI clustering of most other solutes yields nonspecific stoichiometries. It is unclear why Ser8H+ dominates in the case of Ser, and how Ser8H+ forms during ESI. Even the location of Ser8H+ formation is contentious (in solution, in ESI droplets, or elsewhere). Here we unravel key aspects of the L-Ser8H+ formation pathway. Harsh ion sampling conditions promote the collision-induced dissociation (CID) of regular ESI analytes. Unexpectedly, Ser8H+ was seemingly resistant against CID during ion sampling, despite its extremely low MS/MS stability. This unusual behavior reveals that Ser8H+ forms during ion sampling. We propose the following pathway: (1) Nonspecific Ser clusters are released when ESI droplets evaporate to dryness. These initial clusters cover a wide size range, from a few Ser to hundreds or thousands of monomers. (2) The clusters undergo dissociation during ion sampling, mostly via successive loss of neutral monomers. For any source activation voltage, there is a sub-population of clusters for which this CID cascade tends to terminate at the octamer level, culminating in Ser8H+-dominated product distributions. Mobile proton molecular dynamics simulations were used to model the entire pathway. Ser8H+ structures formed in these simulations were consistent with ion mobility experiments. The most compact structures resembled the model of Scutelnic et al. (JACS 2018, 140, 7554), with numerous intermolecular salt bridges and H-bonds. Our findings illustrate how the interplay of association and dissociation reactions across phase boundaries can culminate in magic number clusters.
