# Carbonyl Composition and Electrophilicity in Vaping Emissions of Flavored and Unflavored E-Liquids
###### Abstract
[29] employed global electrophilicity index (\(\omega\)) and local site-specific parameters (energy-weighted local electrophilicity, \(\omega^{\text{E}}\)) and local charge-limited local electrophilicity (\(\omega^{\text{q}}\)) to predict reaction rates of 31 \(\alpha\),\(\beta\)-unsaturated carbonyls toward GSH. Global and local electrophilicity parameters correlated well with experimental values with \(r^{2}\) values around 0.88 and 0.89, respectively, which demonstrate sufficient applicability of computational approaches to predict carbonyls' chemical reactivity [29]. [PERSON] et al. [30] developed a model that uses \(\omega^{\text{q}}\) at the \(\beta\)-carbon of Michael-type acceptors to predict the kinetic rate constants of 66 compounds (aldehydes and ketones) toward GSH (k\({}_{\text{GSH}}\)), and predicted k\({}_{\text{GSH}}\) values correlated well with experimental rate constants with \(r^{2}\) of 0.91. [PERSON] and [PERSON] et al. [28] correlated \(\omega\) values of 10 carbonyls with experimental consumption rates of dithiothreitol (k\({}_{\text{DIT}}\)), a commonly used assay to estimate the oxidative potential of atmospheric aerosols [31]. The findings revealed a strong relationship between \(\omega\) and k\({}_{\text{DIT}}\) values with approximate \(r^{2}\) values of 0.84 and 0.99 for simple and \(\alpha\),\(\beta\)-unsaturated carbonyls, respectively [28]. Given the potential for adverse health outcomes, many studies have demonstrated the impact of flavoring chemicals on carbonyl production during vaping [11; 12; 32]. [PERSON] and [PERSON] [11] compared aldehydes in vaping emissions of flavored and unflavored e-liquids and reported that flavored e-liquids dominated the production of aldehydes (e.g., formaldehyde, acetaldehyde, acrolein, glyoxal, benzaldehyde, propionaldehyde, and m-tolualdehyde). [PERSON] et al. [12] found aldehyde emission levels were 150-200% higher in flavored e-liquids than unflavored e-liquids. Nevertheless, the formation of carbonyls that are not typically monitored via other reaction routes, such as direct oxidation or degradation of alcohol-containing flavoring compounds, has received less attention. In this study, we aimed to characterize reactive carbonyl species emitted via thermal decomposition and direct oxidation of alcohol moieties in e-liquid ingredients during vaping. The e-liquid base (PG and VG) and four flavored e-liquids (_trans_-2-hexenol, benzyl alcohol, l-(-)-menthol, andlinalool) were prepared in house. We hypothesized that during vaping, _trans_-2-hexenol, benzyl alcohol, l-(-)-menthol andlinalool could produce unique carbonyls, such as _trans_-2-hexenol, benzaldehyde, menthone, and linalool-8-aldehyde(6-hydroxy-2,6-dimethylocta-2,7-dienal), respectively. Emitted carbonyls from flavored and unflavored e-liquids were identified by O-(2,3,4,5,6-pentafluorobenzaryl)hydroxylamine (PFBHA) derivatization coupled to solid-phase microextraction (SPME) using gas chromatography/electron ionization-mass spectrometry (GC/EI-MS). Carbonyl levels were quantified using the 2,4-dinitrophenylhydrazine (2,4-DNPH) derivatization method followed by liquid chromatography/electrospray ionization-quadrupole time-of-flight mass spectrometry (LC/EIS-QTOFMS). To investigate the health implications of carbonyls associated with vaping, formation of carbonyl-GSH adducts were measured using LC/ESI-QTOFMS. The global and local reactivity parameters of selected carbonyl compounds were calculated using computational chemistry methods to predict their chemical reactivity and potential toxicity.