Calculation of the free energy of proton transfer from an aqueous phase toliquid acetonitrile

Protons in liquid phases are stabilized by long-range electrostatic interac tions, hydrogen bonding, and the formation of covalent bonds between H+ and solvent molecules. Thus, a small proton affinity, a low dielectric constan t, or the inability to form hydrogen bonds that characterize many nonaqueou s solvents hinders the transfer of protons from an aqueous phase. As a resu lt, the particle that is readily transferred is a hydrated proton, H2n+1On, rather than the bare proton, H+. Here we present calculations of the free energy of proton transfer from water to Equid acetonitrile, including the dehydrated particle, H+, and two hydrated particles, H3O+ and H9O4+- We use a combination of ab initio density functional, theory and a polarizable co ntinuum model within the self-consistent reaction field method. This allows the first and second solvation shells of the proton to be described explic itly from first principles. Vibrational contributions to the enthalpy and e ntropy have been added in. Values taken from experiment are used for the va porization free energies of water and acetonitrile. Our calculations sugges t that the particle that is readily transferred is H9O4+. The model that be st describes the transfer energetics consists of H9O4+ plus several acetoni trile molecules treated explicitly. For these models, the calculated and ob served transfer free energies agree within 50 kJ/mol. Conversely, calculati ons for H+ or H3O+ lead to transfer energies that are too high. In most H9O P4+ models, the proton remains as a H3O+ species that coordinates to a firs t shell of water molecules and a second shell of solvent molecules hydrogen bonded to the water shell. The connection of these results with the curren t views of hydrated protons in polar environments, such as membrane protein s, is also discussed.