| Abstract
| - The nature of the hydrogen bonding in complexes of alkylimidazoles and substituted carboxylicacids has been studied as a model of the hydrogen-bonding interaction of the proton bridging Nδ1 of His 57and the β carboxyl group of Asp 102 in the active site of chymotrypsin. The interaction has been postulatedto be a low barrier hydrogen bond (LBHB) in the enzyme and also in the model complexes which have asmall ΔpKa. In the present study, enthalpies of complex formation, −ΔHformation, between alkylimidazoles(1-methyl, 1-n-butyl-, and 1-tert-butylimidazole) and a series of carboxylic acids were determined by adiabaticsolution calorimetry in chloroform. In FTIR studies presented here, the concentration of LBHB present inthese complexes was determined. For complexation between dichloropropionic acid and alkylimidazoles forwhich the ΔpKa is small in chloroform, the −ΔHformation values varied from 12 to 15 kcal/mol. Thus in enzymes,where ΔG is similar to ΔH, ΔGformation can be as high as −12 to −15 kcal/mol for LBHBs. If a weak hydrogenbond in the initial E·substrate complex with a ΔGformation of ≤−5 kcal/mol is converted to a low barrier hydrogenbond in the transition state, there will be 7−10 kcal/mol of energy available to lower the activation barrier andaccelerate the reaction by 5−7 orders of magnitude.
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