AB-INITIO QUANTUM-MECHANICAL GAS-PHASE AND REACTION FIELD SOLVATION STUDY ON THE PROTON ABSTRACTION FROM HYDROXYACETALDEHYDE BY FORMATE - IMPLICATIONS FOR ENZYME CATALYSIS

Proton abstraction from a model carbon acid hydroxyacetaldehyde by for mate has been studied using ab initio quantum mechanical calculations up to the MP4(SDQ)/6-31 + G*//HF/6-31 + G* level, Solvation effects a re included using the polarisable continuum method, The calculated ene rgies of several intermediates and transition states of the proton tra nsfer reaction are found to be in reasonable agreement with the availa ble experimental data, Calculations show that the alpha-carbon, which loses a proton in the reaction, retains a substantial amount of sp(3) character in the transition state of the reaction. Therefore the reson ance-stabilised enolate anion product, in which the alpha-carbon is sp (2) hybridised, develops after the transition state has been passed, I nclusion of solvation energies moves the transition state to an earlie r point on the reaction profile. This indicates that in the case of en zyme-catalysed reaction, in which the protein environment presumably c an stabilise an enolate-like structure more efficiently than water doe s, the transition state would be even less enolate-like unless enzymes had other means of enhancing the reaction and making the transition s tate occur later, We discuss how lowering of the intrinsic reaction ba rrier and proton tunnelling may move the transition state of the enzym e-catalysed proton abstraction reaction to a later point on the reacti on profile.