Hydrogen bonding catalysis by water in epoxide ring opening reaction

Area of Science:

• Biochemistry
• Computational Chemistry
• Enzymology

Background:

• Water's catalytic role in enzymes is understudied.
• Aspartate proteases utilize water in their catalytic mechanisms.

Purpose of the Study:

• To investigate the electronic basis of water's co-catalytic role in epoxide ring opening.
• To elucidate the mechanism of water's involvement in aspartate protease catalysis.

Main Methods:

• High-level quantum mechanical calculations (M06-2X/6-31+G(d,p)).
• Analysis of electron density and reduced gradient.
• Electrostatic potential analysis.

Main Results:

• Water forms strong hydrogen bonds, anchoring reactants.
• Water's ionizing power facilitates charge delocalization and stabilizes transition states and intermediates.
• Charge transfer from aspartates to epoxide is enhanced, lowering the reaction barrier.

Conclusions:

• Water plays a crucial co-catalytic role in epoxide ring opening by aspartate proteases.
• The electronic effects of water significantly reduce the reaction barrier.
• This finding may guide research into water's role in other enzymatic reactions.