Publication Date

Fall 2023

Document Type

Thesis

Degree Name

Master of Science

Department

Analytical Chemistry

First Advisor

Dr. Shelley Kumar

Second Advisor

Dr. Walter Henne

Third Advisor

Dr. Stephen Kent

Abstract

In a previous study, several oxygenated fullerene compounds were produced by ozonation of C60 (Buckminsterfullerene) and were identified by elemental analysis and by SALI (surface analysis by laser ionization). Some of these compounds, especially a batch, SK-5, a mixture of C60O1-8, were shown to inhibit activities of HIV-Protease with IC50 (concentration for 50% inhibition) of 1 mg/mol in the in-vitro studies. The oxygenated fullerenes were shown to have epoxide, ketones, and hydroxyl functionalities. As expected, C60 interacted with ozone with alkene functionality and not as an aromatic compound. It was postulated that C60O had epoxide functionality, as a product of ozonation of one of the double bonds of C60; C60O2 had ketone functionalities by Ozonolysis of one of the double bonds of C60; C60O4, C60O6, C60O8 had ketone functionalities by Ozonolysis of successive double bonds of C60. The hydroxyl functionality was likely produced due to interaction of water and the oxygenated fullerenes. In the present study, the interactions of oxygenated fullerenes (small molecules) with HIV-Protease (macromolecules) at the molecular levels were studied via blind docking using AutoDock Vina software to elucidate the mechanism of these interactions. The structures of C60O, C60O2, C60O4, C60O6, C60O8 were generated using Spartan software and were docked with a crystal structure of the HIV-Protease (PR) obtained from The Brookhaven Protein Data Bank using AutoDock Vina. These docking studies showed that the oxygenated fullerenes bound to multiple sites of the HIV-PR with high binding affinities (-10.4 to -8.1 kcal/mol). Nine docking poses were generated for each structure, and the models of each conformation were studied using PyMOL software. The docking models in PyMOL suggest that the high binding affinity is a result of the abundance of strong hydrogen bonds ~2.3Å long across the various C60OX structures. The presence of dipole-dipole and van der waals interactions were also found to have played a significant role in binding, with several conformations exhibiting strong binding (≥ -9.8 kcal/mol) with no hydrogen bonds. Results indicate a strong correlation between the ability of C60OX to produce hydrogen bonds/strong dipole interaction with the HIV-PR and inhibition efficacy.

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