Different protonation equilibria of 4-methylimidazole and acetic acid.

Dynamic protonation equilibria in water of one 4-methylimidazole molecule as well as for pairs and groups consisting of 4-methylimidazole, acetic acid and bridging water molecules are studied using Q-HOP molecular dynamics simulation. We find a qualitatively different protonation behavior of 4-methylimidazole compared to that of acetic acid. On one hand, deprotonated, neutral 4-methylimidazole cannot as easily attract a freely diffusing extra proton from solution. Once the proton is bound, however, it remains tightly bound on a time scale of tens of nanoseconds. In a linear chain composed of acetic acid, a separating water molecule and 4-methylimidazole, an excess proton is equally shared between 4-methylimidazole and water. When a water molecule is linearly placed between two acetic acid molecules, the excess proton is always found on the central water. On the other hand, an excess proton in a 4-methylimidazole-water-4-methylimidazole chain is always localized on one of the two 4-methylimidazoles. These findings are of interest to the discussion of proton transfer along chains of amino acids and water molecules in biomolecules.