The thermochemistry associated with protonated complexes containing one or two glyme (MeOCH(2)CH(2)-OMe, (G1)), diglyme (Me(OCH2CH2)(2)OMe, (G2)), or triglyme (Me(OCH2CH2)(3)OMe (G3)) molecules and 0-3 H2O molecules was measured by pulsed high-pressure mass spectrometry. Comparison of polyether, crown ether, and acetone complexes with H+ and H3O+ shows increasing binding energies with increasing flexibility in the ligands. For example, in protonated clusters containing ligands with a total of four polar groups, the proton is bonded by a total energy of (kJ/mol (kcal/mol)) : four Me(2)CO molecules, 1044.8 (249.7); two G1 molecules, 987.4 (236.0); one G3 molecule, 962.3 (230.0); 12-crown-4, 941.4 (225.0). Stabilization of the proton by dipoles of the free ether groups contributes significantly; for example, 17 and 54 kJ/mol (4 and 13 kcal/mol) in the binding energy within (G1H+ and (G2H+ dimers, respectively. The thermochemistry of H3O+ binding indicates bidentate complexes with one each of G2, G3, and 15-crown-5 molecules and two G1 molecules, with binding energies of 310-352 kJ/mol (74-84 kcal/mol). In these complexes the second OH+.O bond contributes up to 113 kJ/mol (27 kcal/mol). Larger binding energies of 387-475 kJ/mol (93-99 kcal/mol) indicate tridentate complexes of H3O+ With two G1 and two G3 molecules, as well as with 18-crown-6, which is the best complexing agent due to entropy effects. In complexes containing additional water molecules, the thermochemistry suggests that two H2O molecules form a protonated solvent bridge between ether groups in (G1.2H(2)OH+ and (G3.2H(2)OH+. Ab initio calculations show that open and solvent-bridged structures have comparable energies (within 16 kJ/mol (4 kcal/mol)). The calculated barriers to direct and solvent-mediated proton transfer between functional groups are 0-16 kJ/mol (0-4 kcal/mol). The solvent-bridged structures are models for water chains involved in proton transport in biomembranes.