Simple Design of an Enzyme-Inspired Supported Catalyst Based on a Catalytic Triad

Mitchell D. Nothling, Aravindhan Ganesan, Karmen Condic-Jurkic, Eric Pressly, Ashley Davalos, Michael R. Gotrik, Zeyun Xiao, Ezat Khoshdel, Craig J. Hawker, Megan L. O'Mara, Michelle L. Coote, Luke A. Connal

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

Enzyme active sites afford an intricate interplay of functional groups to mediate complex organic and inorganic reactions. Many hydrolytic enzymes use a catalytic triad comprising three different functional residues—(Ser(-OH), Hist(-imidazole), Asp(-CO2H))—that catalyze the hydrolysis of numerous unique substrates. Inspired by this design, we have developed a simple one-step synthesis for preparing a new supported catalytic system in which the three reactive groups of the catalytic triad (alcohol, imidazole, and carboxylate) are incorporated into a single functional unit. These artificial active sites can be coupled to a solid-phase support (Merrifield resin) by copper(I)-catalyzed azide-alkyne cycloaddition “click chemistry,” and their effectiveness as esterolysis catalysts was demonstrated. Furthermore, tuning the local hydrophobicity of the resin particles with an approach analogous to the native enzyme hydrophobic pocket increased the catalytic efficiency. Quantum mechanics and molecular dynamics computational modeling were used to probe the catalytic effect and suggested a concerted two-step mechanism and hydrophobic nanoenvironment similar to that of hydrolytic enzymes.

Original languageEnglish
Pages (from-to)732-745
Number of pages14
JournalChem
Volume2
Issue number5
DOIs
Publication statusPublished - 11 May 2017
Externally publishedYes

Keywords

  • bio-inspired
  • biomimicry
  • catalysis
  • catalytic triad
  • click chemistry
  • enzyme
  • esterolysis
  • quantum mechanics modeling

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