Comparison of collision cross section (CCS)-m/z trendlines of perfluoroalkyl carboxylic acid dimers between Trapped, Traveling Wave and Drift Tube ion mobility spectrometry

Per- and polyfluoroalkyl substances (PFASs) are emerging pollutants of great concern, with over 5,000 compounds currently reported. Non-targeted analyses of these substances by liquid chromatography (LC) coupled to high-resolution mass spectrometry (HRMS) remain challenging due to the possible presence of numerous isobars and isomers, and the low number of available analytical standards. In this regard, the coupling of ion mobility spectrometry (IMS) to conventional LC-HMRS offers new perspectives for PFAS analysis due to the additional IMS separation dimension. Furthermore, the structural descriptor obtained from the collision cross-section (CCS) that can be calculated from the measured ion mobility provides an additional identification parameter. In addition, CCS-m/z trends are observed for compounds with repeating units, such as polymers or PFASs. When trapped IMS (TIMS) is coupled to LC-MS to analyze legacy perfluoroalkyl carboxylic acids (PFCAs), multiple mobility peaks are observed at the m/z of a single deprotonated ion, preventing the determination of an unambiguous CCS as an identifier. Of the peaks detected in the mobilogram of a deprotonated PFCA ion, the one with the lowest CCS was confidently assigned to the deprotonated PFCA ion in its monomeric form. The peak with the highest CCS was assigned to a homodimeric PFCA ion ([2M H] ) that existed prior to ion mobility separation. This dimeric form could be dissociated after mobility separation inside the TIMS instrument into the corresponding deprotonated ion ([M-H]-). All detected monomeric PFCAs shared the same linear relationship between CCS and m/z, suggesting that the addition of CF2 units grows like a cylinder along the axial axis (i.e., in length) while its diameter remains constant (Haler et al., JASMS 2022 33(2):273-283). This was confirmed by computational chemistry calculation using ab-initio and semi-empirical DFT (density functional theory) calculations. For the dimeric PFCA ions, the slope of the trendline was lower than for the corresponding monomers. Furthermore, using CCS values of larger dimers, obtained from a previously reported drift tube IMS (DTIMS) database, the CCS-m/z trendline deviated from linearity and was best fitted with a power regression model (power factor 0.53). This suggests that the proton-bound PFCA homodimer no longer grows as a cylinder but more likely adopts a V-shape connected by the proton bridging the carboxylate extremities. When individual PFCAs were directly injected into a DTIMS instrument, sodium-bound homodimers (2M 2H+Na] ) were also detected and their CCS-m/z trendline was also best fitted with a power regression model. This trendline was obtained using TIMS and traveling wave IMS (TWIMS) instruments and compared. If there is any difference in ion heating during ion mobility separation (Morsa et al., Anal. Chem. 2011 83(14):5775-5782) between the three IMS instruments mentioned, this should influence the overall shape of the dimers, leading to different CCS-m/z trends. The difference in CCS values obtained for asymmetric but isobaric (i.e., sharing the same m/z) PFCA heterodimers could also support the V-shape hypothesis. For this purpose, several mixtures of two PFCA homologs that can form isobaric dimers, e.g., C4+C14, C5+C13, C8+C10, were analyzed.