## 3 Results
### Fluoxetine  
HAT Gibbs free energy (\(\Delta\)G\({}^{\circ}\)HAT) was computed for all the possible sites of fluoxetine (Figure 1) considering five ROSs, i.e., HO\({}^{\bullet}\), HOO\({}^{\bullet}\), CH\({}_{3}\)OO\({}^{\bullet}\), CH\({}_{2}\)=CHOO\({}^{\bullet}\), and CH\({}_{3}\)O\({}^{\bullet}\) (Figure 2). The results are shown in Figure 3 and reported in Table S1. HO\({}^{\bullet}\) is the most reactive and electrophilic oxygen-centered radical; the peroxyl radicals HOO\({}^{\bullet}\) and CH\({}_{3}\)OO\({}^{\bullet}\) are much less reactive, and thus can reach remote cellular locations; CH\({}_{2}\)=CHOO\({}^{\bullet}\) was chosen to mimic larger unsaturated peroxyl radicals; finally, CH\({}_{3}\)O\({}^{\bullet}\) has an intermediate reactivity between HO\({}^{\bullet}\) and the peroxyl radicals.  
The thermodynamic results, i.e., reaction energies are discussed first. Referring to the gas-phase values, it emerges that fluoxetine is selective for HO\({}^{\bullet}\) and alkoxyl radicals, excluding--in this latter case--the sites on the phenyl rings; it is not selective for peroxyl radicals. Focusing on the scavenging of HO\({}^{\bullet}\), HAT is thermodynamically strongly favored from N site 16 and from C sites 7, 14-15 and 17, among which 7 and 15 are associated to the largest (negative) values, i.e., \(-\)26.06 and \(-\)26.88 kcal mol\({}^{-1}\). A similar \(\Delta\)G\({}^{\circ}\)HAT is computed for HAT from N site 16 (\(-\)24.24 kcal mol\({}^{-1}\)) and from C site 17 (\(-\)24.87 kcal mol\({}^{-1}\)). In solvent, the same trends are maintained, the \(\Delta\)G\({}^{\circ}\)HAT becoming more negative with increasing polarity, and the largest negative value is found for HAT from N 16 in water (\(-\)31.41 kcal mol\({}^{-1}\)). When considering CH\({}_{3}\)O\({}^{\bullet}\), in the gas phase, HAT is thermodynamically favored only from sites 7 and 14-17. Meanwhile, \(\Delta\)G\({}^{\circ}\)HAT values are approximately half (in absolute value) those computed for HO\({}^{\bullet}\), except for those associated to C 14 and N 16, which are drastically reduced, changing from \(-\)18.31 and \(-\)24.24 kcal mol\({}^{-1}\) to \(-\)3.81 and \(-\)9.73 kcal mol\({}^{-1}\), respectively. Also, for CH\({}_{3}\)O\({}^{\bullet}\), increasing the solvent polarity results in thermodynamically more favored reactions. The reactivity of C sites 14 and 15 of fluoxetine recalls the reactivity of the topologically similar C site 4 in melatonin [46] and zolpidem [38]. By comparing the transfer of the methylene hydrogens to HO\({}^{\bullet}\) in these compounds, which were computed at the same level of theory, [38] the order is zolpidem (\(-\)33.3 kcal mol\({}^{-1}\)) \(>\) melatonin (\(-\)28.9 kcal mol\({}^{-1}\)) \(>\) fluoxetine (\(-\)26.88 kcal mol\({}^{-1}\)). The value of \(\Delta\)G\({}^{\circ}\)HAT involving HO\({}^{\bullet}\) of Trolox is \(-\)38.7 kcal mol\({}^{-1}\)[38]. As mentioned above, fluoxetine is not selective for peroxyl radicals: a negative value of \(\Delta\)G\({}^{\circ}\)HAT, i.e., \(-\)1.23 kcal mol\({}^{-1}\), is computed only for CH\({}_{2}\)=CHOO\({}^{\bullet}\) in water.  
The transition states and thus the activation energies were computed only for the exergonic reactions; they are reported in Table 1.  
Figure 2: Hydrogen atom transfer (HAT) and radical adduct formation (RAF) in fluoxetine (**1**).  
Considering the HAT from C sites 7 and 14, the energy barriers increase almost in all cases when going from the gas phase to benzene and water. Conversely, for the HAT from C sites 15 and 17 and N site 16, the lowest activation energies are computed in water. Kinetically, the easiest scavenging involves HO\({}^{\bullet}\) in water from N 16, which is also the most thermodynamically favored reaction.