Mechanistic Insights into Analyte Charge Enhancement using Mass Spectrometry and Molecular Dynamics Simulations

Electrospray ionization mass spectrometry (ESI-MS) is a powerful technique to investigate proteins and many other analytes. However, many fundamental aspects of ESI remain poorly understood. In this thesis, we use a combination of molecular dynamics (MD) simulations and experiments to gain insights into the hidden complexities of ESI-MS. The structure and reactivity of electrosprayed protein ions is governed by their net charge. In Chapter 2, we sought to uncover the mechanistic basis of La3+-induced charge enhancement. MD simulations showed that irreversible binding via multidentate contacts suppressed La3+ ejection from the vanishing droplets, such that the resulting gaseous proteins carried significantly more charge. In Chapter 3, we examined the supercharging effects of sulfolane on the ESI behavior of salt clusters using similar methods. Spiking NaI solutions with sulfolane resulted in the formation of highly charged cluster ions. MD simulations illustrate that sulfolane stabilizes the cluster to support additional charge. These results demonstrate that the combination of MS experiments and MD simulations can uncover intricate aspects of ESI mechanisms