How Water Exclusion Accelerates Reactions in Enzyme Active Sites and Supramolecular Cavitands

Area of Science:

• Biochemistry
• Physical Chemistry
• Chemical Kinetics

Background:

• Enzyme catalysis is a major scientific challenge.
• Reactions in low-density water and gas phases are significantly faster than in bulk water.
• This suggests water exclusion plays a role in enzyme acceleration.

Purpose of the Study:

• To investigate the role of water exclusion in enzyme active sites.
• To understand the physical chemistry principles behind accelerated reactions in non-bulk water environments.
• To explore if similar acceleration can be achieved in non-enzymatic systems.

Main Methods:

• Analysis of existing reports on reaction rates in different water densities and phases.
• Application of statistical mechanical scaled particle theory to liquid water.
• Theoretical modeling of cavity expansion entropy costs for transition states.

Main Results:

• Low-density water significantly accelerates reactions by reducing entropy costs associated with cavity expansion.
• Enzymes likely accelerate reactions by creating active sites that exclude bulk water.
• This general phenomenon explains a significant portion of enzymatic acceleration.

Conclusions:

• Enzyme active sites accelerate reactions primarily by excluding bulk water, reducing entropic penalties.
• The observed accelerations are linked to the inherent slowness of reactions in bulk water.
• Hydrophobic supramolecular cavitands may also catalyze reactions through a similar water-exclusion mechanism.