Enthalpic studies of complex formation between carboxylic acids and 1-alkylimidazoles

The nature of the hydrogen bonding in complexes of alkylimidazoles and subs tituted carboxylic acids has been studied as a model of the hydrogen-bondin g interaction of the proton bridging N-delta 1 of His 57 and the beta carbo xyl group of Asp 102 in the active site of chymotrypsin. The interaction ha s been postulated to be a low barrier hydrogen bond (LBHB) in the enzyme an d also in the model complexes which have a small Delta pK(a). In the presen t study, enthalpies of complex formation, -Delta H-formation, between alkyl imidazoles (1-methyl, 1-n-butyl-, and 1-tert-butylimidazole) and a series o f carboxylic acids were determined by adiabatic solution calorimetry in chl oroform. In FTIR studies presented here, the concentration of LBHB present in these complexes was determined. For complexation between dichloropropion ic acid and alkylimidazoles for which the Delta pK(a) is small in chlorofor m, the -Delta H-formation values varied from 12 to 15 kcal/mol. Thus In enz ymes, where Delta G is similar to Delta H, Delta G(formation) can be as hig h 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 s tate, there will be 7-10 kcal/mol of energy available to lower the activati on barrier and accelerate the reaction by 5-7 orders of magnitude.