Polarizability: a promising descriptor for selecting di-substituted arene supercharging reagents used during electrospray ionization mass spectrometry (ESI-MS); A DFT Study

Published: 9 May 2022| Version 1 | DOI: 10.17632/nvk8hrwgrn.1
Daniel Abaye,


During electrospray ionization mass spectrometry (ESI-MS) analysis of proteins, the addition of supercharging agents allows for adjusting the maximal charge state, affecting the charge state distribution, and increases the number of ions reaching the detector thus, improving signal detection. Supercharging reagents with higher polarizability values should generate greater signal intensity and increase multiple charging. Molecular polarizability is a vital descriptor for explaining intermolecular interactions. Method We employed DFT-derived descriptors and computed molecular polarizability for ten sets of di-substituted (ortho, meta, para isomers) arene supercharging reagents, with reported use during ESI experiments. Calculations employed the density functional/Hartree-Fock hybrid model, B3LYP and the 6-311++G (2df, 2p) basis set as implemented in the Gaussian 09 program. All structural optimizations were done without symmetry restrictions. All optimized structures were subjected to normal mode analysis to verify the nature of the stationary points located. The geometries of the supercharging compounds were optimized as either the neutral or the anion species. The atomic inputs were ionization potential (IP), electron affinity (EA), electronegativity (χ), hardness (ƞ), chemical potential (µ), and dipole moment (D). We determined that the para isomers showed the highest polarizability values in nine out of the ten sets (Table 1). Polarizability also increased with increasing complexity of the substituents on the benzene ring. Polarizability correlated positively with IP, EA, χ, ƞ, and D, and negatively with chemical potential (Figure 1). Our DFT study predicts that the para isomers of di-substituted arene isomers will elicit the strongest ESI responses. Future experiments to compare the isomers are planned to establish this premise.


Steps to reproduce

To calculate polarizability, the atomic inputs were ionization potential (IP), electron affinity (EA), electronegativity (χ), hardness (ƞ), chemical potential (µ), and dipole moment (D). The atomic values were determined from the following equations: IP = - E^HOMO EA = - E^LUMO χ = -1⁄2 (E^(HOMO )+E^LUMO) µ = 1⁄2 (E^(HOMO )+ E^LUMO) ƞ = 1⁄2 (E^(HOMO )- E^LUMO) Where EHOMO and ELUMO are the energies of the highest occupied molecular orbital and lowest unoccupied molecular orbital, associated with these atomic properties for each element in the compounds under investigation. A manuscript has been submitted to Royal Society Open Science for publication.


University of Health and Allied Sciences


Mass Spectrometry, Density Functional Theory Study, Electrospray Ionization