Highly Charged Protein Ions: The Strongest Organic Acids to Date

Muhammad A Zenaidee; Michael G Leeming; Fangtong Zhang; Toby T Funston; William A Donald

doi:10.1002/anie.201702781

Highly Charged Protein Ions: The Strongest Organic Acids to Date

Angew Chem Int Ed Engl. 2017 Jul 10;56(29):8522-8526. doi: 10.1002/anie.201702781. Epub 2017 May 4.

Authors

Muhammad A Zenaidee¹, Michael G Leeming², Fangtong Zhang¹, Toby T Funston¹, William A Donald¹

Affiliations

¹ School of Chemistry, University of New South Wales, Sydney, NSW, 2052, Australia.
² School of Chemistry and Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, Victoria, 3010, Australia.

PMID: 28471085
DOI: 10.1002/anie.201702781

Abstract

The basicity of highly protonated cytochrome c (cyt c) and myoglobin (myo) ions were investigated using tandem mass spectrometry, ion-molecule reactions (IMRs), and theoretical calculations as a function of charge state. Surprisingly, highly charged protein ions (HCPI) can readily protonate non-polar molecules and inert gases, including Ar, O₂ , and N₂ in thermal IMRs. The most HCPIs that can be observed are over 130 kJ mol^-1 less basic than the least basic neutral organic molecules known (tetrafluoromethane and methane). Based on theoretical calculations, it is predicted that protonated cyt c and myo ions should spontaneously lose a proton to vacuum for charge states in which every third residue is protonated. In this study, HCPIs are formed where every fourth residue on average is protonated. These results indicate that protein ions in higher charge states can be formed using a low-pressure ion source to reduce proton-transfer reactions between protein ions and gases from the atmosphere.

Keywords: electrospray ionization; gas-phase basicity; ion-molecule reactions; mass spectrometry; proteins.

Publication types

Research Support, Non-U.S. Gov't