The nature of the hydrogen bonding in complexes of alkylimidazoles and substituted carboxylic acids has been studied as a model of the hydrogen-bonding interaction of the proton bridging N-delta 1 of His 57 and the beta carboxyl group of Asp 102 in the active site of chymotrypsin. The interaction has been postulated to be a low barrier hydrogen bond (LBHB) in the enzyme and also in the model complexes which have a small Delta pK(a). In the present study, enthalpies of complex formation, -Delta H-formation, between alkylimidazoles (1-methyl, 1-n-butyl-, and 1-tert-butylimidazole) and a series of carboxylic acids were determined by adiabatic solution calorimetry in chloroform. In FTIR studies presented here, the concentration of LBHB present in these complexes was determined. For complexation between dichloropropionic acid and alkylimidazoles for which the Delta pK(a) is small in chloroform, the -Delta H-formation values varied from 12 to 15 kcal/mol. Thus In enzymes, where Delta G is similar to Delta H, Delta G(formation) can be as high as -12 to -15 kcal/mol for LBHBs. If a weak hydrogen bond in the initial E.substrate complex with a Delta G(formation) of % -5 less than or equal to-5 kcak/mol is converted to a low barrier hydrogen bond in the transition state, there will be 7-10 kcal/mol of energy available to lower the activation barrier and accelerate the reaction by 5-7 orders of magnitude.