The Effect of Organic Modifiers on Electrospray Ionization Charge-State Distribution and Desorption Efficiency for Oligonucleotides

  • Buyun Chen
  • Sadie F. Mason
  • Michael G. Bartlett
Research Article
First Online:
Received:
Revised:
Accepted:

Abstract

The chemical composition of the solution has a critical impact on the electrospray desorption efficiency of oligonucleotides. Several physiochemical properties of various organic modifiers were investigated with respect to their role in the desorption process of oligonucleotides. The Henry’s Law Constant, which reflects the volatility of alkylamines, was found to have a prominent effect on both the electrospray charge state distribution and desorption efficiency of oligonucleotides. Alkylamines with higher \( \mathrm{k}_{\mathrm{H,cc}}\left( {\mathrm{aq}/\mathrm{gas}} \right) \) values such as hexylamine, piperidine, and imidazole reduced the charge state distribution by forming complexes with the oligonucleotide and dissociating from it in the gas phase, while alkylamines with extremely low \( \mathrm{k}_{\mathrm{H,cc}}\left( {\mathrm{aq}/\mathrm{gas}} \right) \) values reduced the electrospray charge state distribution by facilitating ion emission at an earlier stage of the electrospray desorption process. Ion-pairing agents with moderate \( \mathrm{k}_{\mathrm{H,cc}}\left( {\mathrm{aq}/\mathrm{gas}} \right) \) values do not alter the electrospray charge state distribution of oligonucleotides and their ability to enhance oligonucleotide ionization followed the order of decreasing \( \mathrm{k}_{\mathrm{H,cc}}\left( {\mathrm{aq}/\mathrm{gas}} \right) \) values. The Henry’s Law Constant also correlated to the impact of the acidic modifiers on oligonucleotide ionization efficiency. Ionization enhancement effects were observed with hexafluoroisopropanol, and this effect was attributed to its low \( \mathrm{k}_{\mathrm{H,cc}}\left( {\mathrm{aq}/\mathrm{gas}} \right) \) and moderate acidity. The comprehensive effects of both alkylamine and hexafluoroisoproapnol on the electrospray ionization desorption of oligonucleotides were also evaluated, and acid-base equilibrium was found to play a critical role in determining these effects.

Key words

Oligonucleotide Electrospray ionization 
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Supplementary material

13361_2012_509_Fig6_ESM.jpg (30 kb)
Supplemental Figure S1

Signal intensity from a 24 mer oligonucleotide in 0–100 mM of TFE or HFIP in 50 % MeOH:H2O (JPEG 29 kb)

13361_2012_509_MOESM1_ESM.tif (32 kb)
High Resolution Image (TIFF 31 kb)
13361_2012_509_Fig7_ESM.jpg (31 kb)
Supplemental Figure S2

pH value of different combinations of 0–100 mM of HFIP and 0–30 mM DIEA in water (JPEG 30 kb)

13361_2012_509_MOESM2_ESM.tif (33 kb)
High Resolution Image (TIFF 32 kb)

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Copyright information

© American Society for Mass Spectrometry 2013

Authors and Affiliations

  • Buyun Chen
    • 1
  • Sadie F. Mason
    • 1
  • Michael G. Bartlett
    • 1
  1. 1.Department of Pharmaceutical and Biomedical Science, College of PharmacyThe University of GeorgiaAthensUSA

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