Sulfolane-Induced Supercharging of Electrosprayed Salt Clusters: An Experimental/Computational Perspective

Area of Science:

• Analytical Chemistry
• Physical Chemistry
• Mass Spectrometry

Background:

• Supercharging agents (SCAs) are known to enhance charge states in electrospray ionization (ESI) of proteins.
• The precise mechanisms behind SCA-mediated supercharging remain incompletely understood.
• Limited research has explored SCA effects on non-protein analytes, such as salt clusters.

Purpose of the Study:

• To investigate the effect of sulfolane, a common SCA, on electrosprayed sodium iodide (NaI) salt clusters.
• To elucidate the atomistic mechanisms underlying sulfolane-induced supercharging of salt clusters using molecular dynamics simulations.

Main Methods:

• Electrospray ionization (ESI) of aqueous NaI solutions with and without sulfolane.
• Analysis of resulting ion clusters using mass spectrometry.
• Atomistic molecular dynamics (MD) simulations of ESI nanodroplets containing Na+/I- and sulfolane.

Main Results:

• ESI of NaI solutions primarily produced singly charged [NaI(n)]+ clusters.
• Addition of sulfolane led to the formation of abundant doubly charged [NaI(n)Sulfolane]2+ clusters, demonstrating supercharging of salt clusters.
• MD simulations confirmed the formation of similar clusters and revealed that sulfolane's slow evaporation and high dipole moment electrostatically stabilize droplets and clusters, facilitating charge retention.

Conclusions:

• This study provides the first experimental evidence of supercharging in electrosprayed salt clusters.
• Charge-dipole stabilization by sulfolane is identified as the key mechanism responsible for enhanced charge states in salt clusters.
• Findings offer new insights into ESI mechanisms and the role of SCAs beyond protein analysis.