Experiment and theory combine to produce a practical negative ion calibration set for collision cross-section determinations by travelling-wave ion-mobility mass spectrometry

RATIONALE There are relatively few cross-section measurements for negatively charged ions. Available calibrants provide sufficient cross-section coverage for the 390 angstrom 2 to 641 angstrom 2 and 1174 angstrom 2 to 3395 angstrom 2 ranges. This is not particularly well suited for determining the collision cross-sections of smaller ions, such as small peptides. METHODS Molecular mechanics/molecular dynamics (MM/MD) simulations, coupled with simulated annealing, were used to find the low-energy molecular conformations of polystyrene (PS) oligomers of length 39 (singly deprotonated) and 513 (doubly deprotonated). The trajectory method in MOBCAL was employed to derive their respective collision cross-sections, O. A calibration plot relating corrected O values to drift times in a Waters Synapt G2 mass spectrometer was used to predict the O values for the -2 to -6 charge states of dT10 DNA. RESULTS The in silico design of a reliable negative ion calibration set for ion mobility spectrometry successfully resulted in the use of a,omega-carboxy-terminated PS oligomers to determine the collision cross-sections of negatively charged ions in the range 132388 angstrom 2. All charge states of dT10 DNA were predicted to within 3% of the referenced values for these ions. CONCLUSIONS a,omega-Carboxy-terminated PS oligomers were found to be an excellent choice to calibrate ion mobility spectrometers to obtain cross-sections for moderately sized ions. Oligomers with fewer, or weaker, interactions among the internal side chains (like poly(ethylene glycol) oligomers) tend to have a wide range of low-energy molecular conformations resulting in large standard deviations in their theoretically predicted collision cross-sections. Copyright (c) 2012 John Wiley & Sons, Ltd.