Melamine and cyanuric acid are widely used in industry and in scientific research. The mixture of melamine and cyanuric acid can form a hydrogen-bonded network structure which has been used as a surface template in supramolecular chemistry. In this work, the thermochemical properties of melamine and cyanuric acid were characterized using mass spectrometry measurements and computational studies. The proton affinity and the gas-phase acidity were determined with the application of the extended Cooks kinetic method. A triple-quadrupole mass spectrometer equipped with an electrospray source was employed for this study. For melamine, the proton affinity, the gas-phase basicity, and the protonation entropy were determined to be 226.2 ± 2.0 kcal/mol, 218.4 ± 2.0 kcal/mol and 26.2 ± 2.0 cal/mol K, respectively. For cyanuric acid, the deprotonation enthalpy, the gas-phase acidity, and the deprotonation entropy were determined to be 330.7 ± 2.0 kcal/mol, 322.9 ± 2.0 kcal/mol and 26.1 ± 2.0 cal/mol K, respectively. The geometries and energetics of melamine, cyanuric acid, and related molecules/ions were calculated at the B3LYP/6-31+G(d) level of theory. The theoretical proton affinity and deprotonation enthalpy were calculated using the corresponding isodesmic proton transfer reactions. The computationally predicted proton affinity of melamine (225.9 kcal/mol) and gas-phase deprotonation enthalpy of cyanuric acid (328.4 kcal/mol) were in good agreement with the experimental results. Melamine is best represented as the imide-like triazine-triamine form and the triazine nitrogen is more basic than the amino group nitrogen. Cyanuric acid is best represented as the keto-like tautomer and the N-H group is the most likely proton donor. Cyclohexane-based molecular switches have been of great interest in recent years. This work focused on the investigations of the thermochemical properties related to the switching process. A group of cyclohexane-based model compounds were selected for this study. The model compounds included trans -2-aminocyclohexanol, trans -4-aminocyclohexanol and trans -2-dimethylaminocyclohexanol. The proton affinities of the compounds were determined using the extended Cooks kinetic method. The values obtained were 238.5 ± 2.0 kcal/mol ( trans -2-dimethylaminocyclohexanol), 225.5 ± 2.0 kcal/mol ( trans -2-aminocyclohexanol) and 220.4 ± 2.0 kcal/mol ( trans -4-aminocyclohexanol). Various molecular structures related to the model compounds and the switching molecules were calculated at the B3LYP/6-31+G(d) level of theory. The theoretical proton affinities of all the molecules investigated were also calculated at the same level of theory using corresponding isodesmic reactions. The results show that the proton affinities decrease as the relative positions of amino and alcohol groups change from ortho to meta to para . The stronger proton affinity of the ortho isomer may be due to the efficient intramolecular hydrogen bonding in the protonated form. The proton affinity of trans -2-dimethylaminocyclohexanol is stronger than that of trans -2-aminocyclohexanol by about 13 kcal/mol. Substitution of hydrogen atoms by methyl groups at nitrogen promotes the intramolecular hydrogen bonding between the amino group and the hydroxyl group upon protonation. This, in turn, may enhance the proton affinity of methylated molecule. Computational studies also show interesting trends for stabilities and proton affinities of the different structures. These data may be useful as a guide for designing efficient conformational switches.