Dwivedi, et al. Gas Phase Chiral Separations by IMS, Anal. Chem, 2006, 8200-8206

In this paper, gas-phase chiral separation of enantiomers of some racemates is claimed to be achieved by ion mobility spectrometry by introducing the dopants S-2-butanol and R-2-butanol. However, results are inconsistent.

Overall

● What were the major flaws of this article?

1) In Figure 4, the curves for S-2-butanol and R-2-butanol should coincide. If S-2-butanol produced a given drift time shift in L-methionine, R-2-butanol should produce the same shift in D-methionine. The shifts are achieved because the enantiomers exist as the clusters S-2-butanol/L-methionine and R-2-butanol/D-methionine. These clusters both have the same size and energetics because they are specular images.

2) The difference in drift time between D and L methionine should be the same with S-2-butanol and R-2-butanol. However, it is larger with S-2-butanol. The explanation of why this is wrong is the same as before

3) The separation between the enantiomers of atenolol is huge compared with the other racemic mixtures. Atenolol is a large molecule, compared to, for example, valinol, and its mobility shift should be small as has been demonstrated in the literature.1,2 However, the change in mobility with the dopant is the same for both molecules. Atenolol has shown only a small absolute mobility shift of 0.7% with 2-butanol in the buffer gas for strong non-chiral interactions;3 for this reason, it is not clear how a large 1.7% mobility shift can be obtained for a weak chiral interaction like the one experienced in Dwivedi’s paper especially because their non-chiral interaction yielded 0% mobility shift: their (R)-atenolol enantiomer did not shift.

4) The relative mobility shifts in absolute values (%ΔK0’) of the enantiomers of protonated methionine was 0.82, calculated as the percentage difference between the mobilities of both enantiomers in a (S)-2-butanol-doped buffer gas; this value was 2.3 for phenylalanine and 1.7 for atenolol. A small ΔEnergy’ for adducts of (S)-2-butanol with the ions investigated has been calculated: only 0.2 Kcal/mol for methionine and 0.9 Kcal/mol for (S)-phenylalanine, too small to explain the relatively large mobility shifts reported in Dwivedi’s paper. Protonated methionine and phenylalanine have shown small mobility shifts (%ΔK0) of -4.2 and -7.2 for large interaction energies of 21.1 and 19.6 Kcal/mol, respectively, when 2-butanol was introduced in the buffer gas at similar conditions;4 this results in 0.20 and 0.37 %ΔK0/Kcal 4 compared to 4.1 and 2.6 %ΔK0/Kcal [Dwivedi’s paper] for protonated methionine and phenylalanine, respectively; results from Dwivedi’s paper are excessively large especially because these values result from strong non-chiral interactions and those from Dwivedi’s paper from weak chiral interactions.

TITLE • The title is short, catchy and informative

ABSTRACT • The aim of the paper is clear and the abstract is short. • It is clear what the study found but the method is not described. • The purpose of the paper was provided and general results are given. Information on the extent of the separations were not given. • There is not an interpretation and conclusion.

INTRODUCTION

• The paper state what is known of this research area, the gap in the knowledge; it is concise and direct. Important studies are referenced.

EXPERIMENTAL

• Experiments are detailed so they can be can repeated • Vendors and their location (instruments and reagents) are given. • This section is rightly written in the past tense

RESULTS AND DISCUSSION • Tables and figures are independent from the text. • Data on precision is given • Limitations and future research areas and applications of the study are supplied.

REFERENCES, • References are relevant and current; they are correctly referenced

1. Fernandez-Maestre R, Wu C, Hill HH. Buffer gas modifiers effect resolution in ion mobility spectrometry through selective ion-molecule clustering reactions. Rapid Commun Mass Spectrom 2012, 26, 19, 2211–2223.
2. Fernandez-Maestre R, Wu C, Hill HH. Using a Buffer Gas Modifier to Change Separation Selectivity in Ion Mobility Spectrometry, Int J Mass Spectrom 2010, 298, 2-9.
3. Fernandez-Maestre, R.; Harden, C.S.; Ewing, R.G.; Crawford, C.L.; Hill Jr., H.H. Chemical Standards in Ion Mobility Spectrometry. Analyst, 2010, 135(6):1433-1442.
4. Fernandez-Maestre R, Meza-Morelos D, Hill HH. Mobilities of amino acid adducts with modifiers in the buffer gas of an ion mobility spectrometer depended on modifier size and modifier-amino acid interaction energy. Int J Mass Spectrom 2015, 380, 21-25.