Charge Retention/Charge Depletion in ESI-MS: Theoretical Rationale

Area of Science:

• Analytical Chemistry
• Physical Chemistry
• Computational Chemistry

Background:

• Gas phase modification in electrospray ionization mass spectrometry (ESI-MS) significantly influences the charge state distribution of peptides and proteins.
• A previous study proposed a charge retention/charge depletion mechanism based on experimental data for Substance P.

Purpose of the Study:

• To theoretically investigate proton transfer processes from charged analytes to solvent clusters.
• To support the proposed charge retention/charge depletion model through theoretical calculations and experimental validation.

Main Methods:

• Computational modeling of proton transfer pathways and thermochemical stability for (di)amines with methanol and acetonitrile.
• Experimental validation using (di)amines as model systems.

Main Results:

• Both acetonitrile (ACN) and methanol (MeOH) form stable adduct clusters at the protonation site.
• Methanol forms extensive hydrogen-bonded clusters, lowering proton transfer barriers and enabling charge transfer from the analyte.
• Acetonitrile, being aprotic, does not form H-bridged structures, leading to charge retention on the analyte.

Conclusions:

• The study confirms the charge retention/charge depletion model.
• Adding aprotic solvent vapors to the ESI source gas phase favors higher analyte charge states compared to protic solvents.