A Bait-and-Switch Method for the Construction of Artificial Esterases for Substrate-Selective Hydrolysis

Area of Science:

• Supramolecular Chemistry
• Catalysis
• Nanotechnology

Background:

• Enzymes exhibit remarkable selectivity, overriding intrinsic chemical reactivity to transform specific substrates.
• Developing synthetic catalysts that mimic this enzyme-like selectivity, especially for challenging transformations, remains a significant challenge in chemistry.

Purpose of the Study:

• To create highly selective artificial esterases using molecular imprinting within nanoparticles.
• To demonstrate enzyme-like kinetics and substrate selectivity in synthetic catalysts.

Main Methods:

• Utilized micellar imprinting with photocleavable monomers and transition-state analogue templates (phosphonates/phosphates) to form active sites within nanoparticles.
• Engineered doubly cross-linked micelles to create stable, template-complementary binding pockets.
• Postmodified the imprinted micelles by replacing the binding group with a catalytic pyridyl moiety to generate artificial esterases.

Main Results:

• Successfully created artificial esterases with predetermined active site size and shape.
• The catalysts exhibited enzyme-like kinetics and high turnover numbers (hundreds).
• Demonstrated remarkable selectivity, enabling the transformation of less reactive esters in the presence of more reactive ones, attributed to substrate-complementary imprinted sites.

Conclusions:

• Micellar imprinting provides a powerful strategy for designing synthetic catalysts with enzyme-like selectivity and activity.
• These artificial esterases represent a significant advancement in mimicking biological catalysis for selective chemical transformations.
• The imprinted active sites are crucial for achieving high selectivity, overcoming inherent substrate reactivity differences.