Identification of Isomers by Multidimensional Isotopic Shifts in High-Field Ion Mobility Spectra

Abstract

Nearly all molecules incorporate elements with stable isotopes. The resulting isotopologue envelopes in mass spectra tell the exact stoichiometry but nothing about the geometry. Chromatography and electrophoresis at high resolution also can distinguish isotopologues, again without revealing structural information. In high-definition differential ion mobility (FAIMS) spectra, these envelopes universally split in a structure-specific manner, providing a new general approach to isomer delineation. Here, we show that the peak shifts from instances of the same isotope are equal and can be averaged into characteristic elemental shifts, namely C andCl for dichloroanilines (DCA). Matrices of these shifts, including the gas composition dimension, are unique to the structure. Hence, all six DCA isomers (with four making two unresolved pairs) are readily delineated in the C/Cl maps with He/CO buffer gases. Mixtures of coeluting isomers are also distinguished from pure components.

Structurally Informative Isotopic Shifts in Ion Mobility Spectra for Heavier Species

“…The ΔE C ( 13 C) for 3,5 remains the sole decisively negative one and moves even lower: to −0.6 V/cm (at ∼40% He) vs −0.3 V/cm for DCA. 32 The other four DBAs lie closer at ΔE C = 0.2−0.8 V/cm versus spreading over the 0.0−1.0 V/cm range for DCAs. Nonetheless, the 2,4, 2,5, and 2,6/3,4 pair remain fully distinguished at ∼30−40% He.…”

“…All tried DBAs, TBAs, and MIAs make protonated 1+ ions in ESI, with H + presumably on the N atom. The ion flux for DBAs and TBAs depends on the isomer, minimizing for DBA 2,6 (as with DCAs) 32 and TBA 2,4,6. The two large acidic Br atoms bracketing N apparently reduce its proton affinity and/ or shield it from protonation.…”

“…The mass spectra for DBAs and TBAs ( Figure 1) agree with the isotopic distributions computed ( Table 1) with unit resolution: disentangling isobars spaced by <0.01 Da requires R > 3 × 10 4 that is beyond the capability of Paul ion trap in any mode (although available from Fourier-transform MS). 32 As with lighter haloanilines, 30−32 one stoichiometry dominates each nominal mass. For DBAs or TBAs, the peaks Tables 1 and 2 Journal of the American Society for Mass Spectrometry Research Article at 1 and 2 Th above the base are due to, respectively, 13 C at >93% and 81 Br at 99.9%.…”

“…The quantitative ΔE C trends (Figure 4a−c) reveal further parallels to DCAs. 32 The three 13 C shifts [ΔE C (251−250), ΔE C (253−252), ΔE C (255−254)] are virtually constant for each isomer but vary between them. The |ΔE C | values increase at higher He content, and the expanding interisomer ΔE C spread maximizes specificity at 43% He.…”

“…The structural specificity has actually improved for DCAs compared to MCAs, as the greater number of measurable peaks in the natural isotopic envelopes and emergence of informative 37 Cl shifts augmented the dimensionality of ΔE C set. 32 That suggested the feasibility of method for substantially heavier ions.…”