Dunathan stereoelectronic hypothesis

Dunathan stereoelectronic hypothesis is a concept in chemistry to explain the stereospecific cleavage of bonds using pyridoxal phosphate. This occurs because stereoelectronic effects controls the actions of the enzyme.^[1]

History

Before the correlation between fold type and reaction correlation of proteins were understood, Harmon C. Dunathan, a chemist at Haverford College^[2] proposed that the bond that is cleaved using pyridoxal is perpendicular to the system.^[3] Though an important concept in bioorganic chemistry, it is now known that enzyme conformations play a critical role in the final chemical reaction.

Mode of action

The transition state is stabilized by the extended pi bond network (formation of anion).^[4] Furthermore hyperconjugation caused by the extended network draws electrons from the bond to be cleaved, thus weakening the chemical bond and making it labile^[5] The sigma bond that is parallel to the pi bond network will break.^[6] The bond that has the highest chance of being cleaved is one with the largest HOMO-LUMO overlap.^[7] This effect might be effected by electrostatic effects within the enzyme.^[8]

Applications

This was seen in transferase and future interests lie in decarboxylation in various catalytic cycles.^[9]