Hydrogen bond networks in protonated acetone/water clusters are stabilized by H3O+(Me2CO)2 centers, and the stabilizaton increases with further acetone content. For example, proton transfer from neat water (H2O)6H+ clusters to form mixed (Me2CO)3(H2O)3H+ clusters is exothermic by 80 kJ/mol (19 kcal/mol), due to strong hydrogen bonding of the carbonyl groups; in a series of mixed clusters B3(H2O)3H+, the stability of the hydrogen bond network correlates with the proton affinities PA(B). In diketone models of adjacent peptide links, the proton is stabilized by internal hydrogen bonds between the carbonyl groups. The internal bonds can be significant, for example, 31 kJ/mol (7 kcal/mol) in (MeCOCH2CH2COMe)H+, but proton transfer through the internal bond has a high barrier. However, water molecules can bridge between the CO groups. In these bridges, the proton remains on an H3O+ center, in both acetone/water and diketone/water systems. With a further H2O molecule, the diketone/water cluster (MeCOCH2CH2COMe)(H2O)2H+ and diamide/water clusters form two-water H3O+âââH2O bridges, which allow proton transfer between the CO groups with a small barrier of <12 kJ>/mol (<3 kcal>/mol). The cluster models suggest several roles for hydrogen bonds in proton transport through membranes. (1) Ionic hydrogen bonds involving polar amide groups stabilize ions by up to 135 kJ/mol (32 kcal/mol) in clusters and can similarly stabilize ions in membrane water chains and enzyme centers. (2) The proton can remain on an H3O+ center and, therefore, remain delocalized and mobile in water chains, despite the stronger basicities of the surrounding amide groups. This effect results from electrostatic balancing of opposing peptide amide dipoles. (3) In the water chains, H3O+âââH2O bridges between peptide amide groups can provide low-energy pathways for proton transport.