Date of Award

August 2021

Document Type


Degree Name

Doctor of Philosophy (PhD)



Committee Member

Brian Dominy

Committee Member

Steve Stuart

Committee Member

Daniel Whitehead

Committee Member

Leah Casabianca

Committee Member

Emil Alexov


In this dissertation, discrete molecular dynamics (DMD) and molecular dynamics (MD) were performed to explore the catalysis of H-D-Pro-Pro-Glu-NH2 derivatives in an aqueous solution. The amphiphilic nature of H-D-Pro-Pro-Glu-NH2 derivatives drives the formation of an emulsion and allows for excellent reactivity and selectivity on catalyzing Michael addition reactions between aldehydes and nitroolefins. The DMD and MD simulations provide a detailed atomic-level understanding of emulsion structure and offer insight into the role of emulsion structure on catalysis.

Chapter 2 studied the catalysis of H-D-Pro-Pro-Glu-NH-C12H25 on catalyzing Michael addition of butanal to nitrostyrene in an aqueous environment. A hypothesis has been proposed that the catalyst H-D-Pro-Pro-Glu-NH-C12H25 aggregates with reactants to form an emulsion, which provides a micro-hydrophobic environment that similar to that in organic solvents. The hypothesis was tested by sampling the emulsion structure with DMD and MD methods. The results illustrated that the hydrophobic environment provided by emulsion facilitates the formation of enamine intermediate. The highly concentrated nitrostyrene assembled by catalysts makes the carbon-carbon bond formation between enamine intermediate and nitrostyrene occur rapidly.

Chapter 3 explored the role of different derivatives on emulsion formation and gave insights into the reaction mechanism. Two different H-D-Pro-Pro-Glu-NH2 derivatives (H-D-Pro-Pro-Glu-NH-C12H25 and H-D-Pro-Pro-Glu-N-(C12H25)2) have been studied by DMD and MD simulations. The experimental results demonstrated that the H-D-Pro-Pro-Glu-N(C12H25)2 shows lower reactivity on catalyzing the Michael addition reaction of butanal to nitrostyrene under an aqueous environment in comparison to H-D-Pro-Pro-Glu-NH-C12H25. The atomic-level understanding of emulsion structure formed by catalysts suggests that the extra hydrophobic alkyl chain C12H25 at C-terminal of H-D-Pro-Pro-Glu-N-(C12H25)2 provides better protection of active site (D-proline) from water in comparison to that of H-D-Pro-Pro-Glu-NH-C12H25. This better water exclusion of D-proline is responsible for the lower reactivity.

Chapter 4 aimed to understand the scope of substrates on H-D-Pro-Pro-Glu-NH-C12H25 catalyzed the Michael addition reaction of aldehydes to nitrostyrene in water. The experimental results showed that the reaction rate does not only depend on the reactivity of the substrates but also heavily on the structure of the emulsion. Three different aldehydes were studied and emulsion structures of three aldehyde systems have been generated by DMD and MD simulations respectively. It was found that increasing the hydrophobicity of aldehyde increases the concentration of aldehyde at the oil-water interface, which contributes to the rate enhancement.



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