# Bead-Ejection Scenario in Electrospray Ionization of Multidomain Nucleic Acids

## TL;DR

The paper explores how multidomain nucleic acids retain their structure during ionization, revealing new insights into their charge and conformation behavior.

## Contribution

The study introduces the bead-ejection scenario as a new mechanism for ion production in multidomain nucleic acids during electrospray ionization.

## Key findings

- Multidomain nucleic acids show multimodal charge-state and collision cross section distributions.
- Bead-ejection scenario explains ion production for intermediate charge states in these nucleic acids.
- Local structures are preserved in ions charged above the Rayleigh limit, indicating folded subunits.

## Abstract

Understanding how biomolecules acquire their charge and
retain
their solution conformation during electrospray ionization (ESI) is
crucial for native mass spectrometry (native MS) interpretation. Here,
we examine the charging and gas phase conformation of nucleic acid
constructs comprising folded G-quadruplex “beads” linked
by unstructured polythymine regions. Under physiological ionic strength,
these oligonucleotides exhibit a multimodal charge-state and collision
cross section distribution, revealing multiple conformational ensembles,
in contrast to the unimodal profiles typically observed for shorter
oligonucleotides. Native MS observations for intermediate charge states
are compatible with ion production via the recently proposed bead-ejection
scenario, in addition to the charge residue scenario for low charge
states and chain ejection for the highest charge states or for sequences
with thymine overhangs on both ends. The preservation of the local
structures in ions charged above the Rayleigh limit helps to infer
the presence of folded subunits. The position of the G-quadruplex
subunit and ionic strength govern the charging and retention of G-quadruplex
folded regions. Our findings broaden the existing conceptual framework
underpinning nucleic acid ionization.