## 3 Results and Discussions
### \(H_{3}O^{+}\) Reagent Ion Measurements with Propofol  
Given that the proton affinity (PA) and gas phase basicity (GB) for propofol are not available in the literature, we have used the Gaussian09W program with the GaussView05 for Windows interface and the B3 LYP functional with 6-31 + G (d,p) basis set at 298 K [31] to provide calculated values. We have calculated that the PA and GB of propofol at 298 K are 770 kJ mol\({}^{-1}\) and 747 kJ mol\({}^{-1}\), respectively, which are higher than the corresponding calculated values for the water monomer (PA 684 kJ mol\({}^{-1}\) and GB 653 kJ mol\({}^{-1}\)), but less than those values for the water dimer (PA 842 kJ mol\({}^{-1}\) and GB 777 kJ mol\({}^{-1}\)). Thus, of the two major reagent ions present in the drift tube of the PTR-ToF-MS, namely H\({}_{3}\)O\({}^{+}\) and H\({}_{3}\)O\({}^{+}\).H\({}_{2}\)O (see Figure 1a), only H\({}_{3}\)O\({}^{+}\) can efficiently transfer a proton to propofol. This proton transfer results in the protonated parent, C\({}_{12}\)H\({}_{19}\)O\({}^{+}\), at _m/z_ 179.144, which is found to dominate the product ion distribution up to about 170 Td. Above 170 Td protonated phenol, C\({}_{6}\)H\({}_{7}\)O\({}^{+}\) at _m/z_ 95.050, resulting from collision-induced dissociation processes, becomes the dominant product ion. One other product ion, also resulting from collision-induced dissociation, is observed at _m/z_ 137.097, which is assigned to be protonated 2-(1-methylethyl)-phenol (C\({}_{9}\)H\({}_{13}\)O\({}^{+}\)). Protonated 2-(1-methylethyl)-phenol results from a loss of C\({}_{3}\)H\({}_{6}\) from protonated propofol, and then a sequential loss of another C\({}_{3}\)H\({}_{6}\) from C\({}_{9}\)H\({}_{13}\)O\({}^{+}\) leads to the protonated phenol product. [PERSON] et al. [1] also report three product ions but only at nominal _m/z_ values of _m/z_ 179, _m/z_ 137 and _m/z_ 95 in their 2003 PTR-MS study. With the higher resolving power of the mass spectrometer available in this study, their molecular assignments are now confirmed.  
A potential reaction pathway that should perhaps be expected following the transfer of a proton from H\({}_{3}\)O\({}^{+}\) to propofol is that which leads to an elimination of H\({}_{2}\)O, as depicted in Equation (1):  
\[\mathrm{H_{3}O^{+}+C_{12}H_{18}O\ \overset{yields}{\rightarrow}\ C_{12}H_{17} ^{+}+2H_{2}O\ \Delta H}=+46\ kJ\ mol^{-1}\ \Delta G=-11\ kJ\ mol^{-1}, \tag{1}\]  
with the changes in enthalpy (\(\Delta\)H) and free energy (\(\Delta\)G) having been calculated using density functional theory calculations using a temperature of 298 K [31]. Although the temperature in the drift tube was maintained at a higher temperature than 298 K, namely 353 K, and the effective translational temperature of the ions is even greater due to the energy they gain in the electric field, the actual temperature used in the calculations is not crucial to the interpretation of the results. This is because the energetics of thermodynamics (and particularly \(\Delta\)G rather than \(\Delta\)H) are only being used as a guide to aid in the interpretation of the experimental observations. Given that the reaction pathway (1) is slightly exoergic at 298 K (\(\Delta G=-11\ kJ\ mol^{-1}\)), it is surprising that dissociative proton transfer leading to the product ion C\({}_{12}\)H\({}_{17}\)\({}^{+}\) is not observed, especially considering that the effective translational temperature of the H\({}_{3}\)O\({}^{+}\) ions in the drift tube is substantially higher than that of 298 K. We have no explanation as to why the dissociative pathway (1) is not observed, and hence we propose to undertake further theoretical and experimental investigations in the hope to be able to shed some light on this observation.