To measure the basicity of organic compounds in the gas phase, the proton affinity (PA) can be used. The proton affinity is defined as the negative of the enthalpy change for the reaction M (g) + H + (g) →MH + (g), being M a chemical species: molecule, radical or atom . The higher the PA, the stronger the conjugate base and the weaker the conjugated acid in the gas phase. The PA value also illustrates the role of hydration in Brønsted acidity in the aqueous phase . The relationships between the energies of the highest molecular orbitals (HOMO and other frontier orbitals; HOMO: Highest Occupied Molecular Orbital) and PA are often present for families of compounds, such as phenols. However, for a large number of compounds, the energies of their HOMOs do not present a good correlation with PA values . Accordingly, the question arose: why are HOMO energies good acid-base descriptors for some compounds and not for others? Faced with such limitations, another approach has emerged to understand chemical reactivity: the concept of FERMO (Frontier Effective for Reaction Molecular Orbital), proposed by Silva and Ramalho .