UC Berkeley

Chapter 1: A brief overview of enzyme-inspired materials is provided. It covers supramolecular systems, polymeric materials, de novo designed enzymes, and small molecule micelle catalysts.

Chapter 2: Nano-reactor type random heteropolymers (RHPs) catalysis was studied. RHPs collapsed in nonpolar solvent, toluene, forming a hydrophilic interior. In polar microenvironments of RHPs, the rate of aminolysis reaction was enhanced although in toluene, there was no significant background reaction. RHP’s microenvironment was key to catalysis. The composition effects and additive effects were investigated.

Chapter 3: New random heteropolymers (RHPs) were designed to mimic terpene cyclases. Squalene-hopene cyclase (SHC) was analyzed as a representative example of terpene cyclases. Its surface and active site composition as well as its sequence were examined. Analysis showed negatively charged aspartic acid 377 was incorporated in hydrophobic active site and could stabilize a carbenium intermediate. Also, the enzyme utilized cation-π interactions to stabilize carbocation intermediates. Thus, to imitate electrostatic stabilization and cation-π interactions, new RHPs were designed and studied. Statistical sequence study showed effective incorporation of negatively charged side chain in hydrophobic microenvironment in rationally designed RHP (S15).

Chapter 4: With rationally designed random heteropolymers (RHPs) in chapter 3, cyclization reaction of citronellal (CA) was tested. The newly designed RHPs were synthesized via RAFT polymerization. The polymer’s hydrophobic microenvironment was explored using solvatochromic study with pyrene. X-ray absorption near edge structure (XANES) technique was applied to distinguish the population of negatively charged monomers in hydrophobic environment. Then, the RHP-CA complex was studied with a variety of NMR techniques. Proton NMR showed the complexation was rapid and CA’s environment changed to more hydrophobic. Diffusion NMR demonstrated complexation of RHP with CA by showing the same diffusivity from CA and RHP. Nuclear Overhauser Effect Spectroscopy illustrated interesting RHP-CA interactions including possible electrostatic interactions and cation-π interactions. Those studies explained RHPs selective catalysis in water solution.

Chapter 5: In Chapter 5, random heteropolymer (RHP)’s substrate scope was examined. Enzymes have substrate specificity due to its internal unique structures. However, enzyme’s substrate specificity could have a negative impact on industrial applications since their structures should be modified to use different substrates. In contrast, RHPs, as a more flexible system, can catalyzed different substrates when the reaction mechanism is similar. Thus, the rationally designed terpene cyclase mimic RHP was applied to another reaction which also proceeded carbenium intermediates. Here, RHPs’ versatility was studied by investigation of catalytic study of α-pinene oxide isomerization.