Native mass spectrometry probes ions generated using electrospray ionization from aqueous buffers with physiologically relevant pH and ionic strengths. �Native-like ions� can retain significant memories of their native stoichiometries and structures, but concerns of nonspecific aggregation during the desolvation of electrospray droplets and the relationship between ion charge and structure persist. Here, experiments and models are used to understand the evolution of native-like ions, from initial droplets to final desolvated ion. Most studies of the initial stages of electrospray have probed droplets formed using electrospray from large internal diameter capillaries (10s-100s �m) with externally controlled flow rates, whereas most native mass spectrometry experiments use electrokinetically controlled solution flows through smaller inner diameter capillaries. We measured initial droplet size distributions produced by an electrokinetically controlled nanoelectrospray source and use Monte Carlo simulations to quantify the extent of nonspecific aggregation that is possible during desolvation. These results indicate that the initial droplets produced during electrokinetically controlled nanoelectrospray ionization can be small enough to preserve oligomeric distributions from solution, even in the absence of droplet fission. After droplet desolvation, the charge states measured for the resulting native-like cations and anions depend on the Rayleigh limit and competing ion evaporation processes (Allen et al. Anal. Chem. 2013 , 85, 12055-12061). We have developed a more detailed understanding of the roles of these two factors using ion mobility derived collision cross sections and complementary results measured from solutions containing supercharging reagents. These results suggest that supercharging can modestly increase the charge states of native-like ions by suppressing ion evaporation, but that disruption of structure may be concomitant with more extensive supercharging. More generally, these results provide insights into the effects of electrospray conditions on the structures of the resulting gas-phase ions and the correlation between the properties of those ions and the corresponding condensed-phase biomolecules.

Native electrospray ionization: From initial droplets to final ions

248th National Meeting (2014)

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