Hydrogen bonds are the presiding concepts for arranging the three-dimensional forms of biological molecules like proteins, carbohydrates and nucleic acids, and acts as guides for proton transfer reactions. Gas-phase acidity and pKa calculations in dimethyl sulfoxide on a line of polyhydroxylated piperidines specify that multiple hydrogen bonds lead to enhance acidities.
The gas-phase acidity (GPA) of polyhydroxylated piperidines was investigated by MP2/6-311++G(d,p)//B3LYP/6-311++G(d,p) method. For each structure, varied primary and secondary hydroxyl groups were deprotonated. The natural bond orbital (NBO) and quantum theory of atoms in molecules (QTAIM) analyses have also been used to realize the character of the hydrogen bonding interactions in these compounds.
The results show by adding each hydroxyl group, ΔHacid in the gas phase (it becomes less endothermic) and pKa value in the solution phase was decreased. Therefore, intramolecular hydrogen bonds lead to enhance the acid strength. In both the gas phase and solution phase, the β-Nojrimycin-OH2 (β-1-OH2) was found to be the most acidic compound with calculated gas-phase acidity (GPA) of 349.4 kcal.mol-1 and the pKa value of 22.0 (8.0 pKa units more acidic than 1-propanol).
It was also shown, applying the polarized continuum model (PCM), there is a superior linear correlation with the gas phase acidities (GPAs) of polyhydroxylated piperidines and their calculated pKa (DMSO) values.