Ab initio quantum mechanical gas phase and reaction field solvation study on the proton abstraction from hydroxyacetaldehyde by formate: implications for enzyme catalysis

Abstract

Proton abstraction from a model carbon acid hydroxyacetaldehyde by formate has been studied using ab initio quantum mechanical calculations up to the MP4(SDQ)/6-31+G**//HF/6-31+G* level. Solvation effects are included using the polarisable continuum method. The calculated energies of several intermediates and transition states of the proton transfer reaction are found to be in reasonable agreement with the available experimental data. Calculations show that the α-carbon, which loses a proton in the reaction, retains a substantial amount of sp³ character in the transition state of the reaction. Therefore the resonance-stabilised enolate anion product, in which the α-carbon is sp² hybridised, develops after the transition state has been passed. Inclusion of solvation energies moves the transition state to an earlier point on the reaction profile. This indicates that in the case of enzyme-catalysed reaction, in which the protein environment presumably can stabilise an enolate-like structure more efficiently than water does, the transition state would be even less enolate-like unless enzymes had other means of enhancing the reaction and making the transition state occur later. We discuss how lowering of the intrinsic reaction barrier and proton tunnelling may move the transition state of the enzyme-catalysed proton abstraction reaction to a later point on the reaction profile.