Date of Award
Spring 4-17-2024
Degree Type
Thesis
Degree Name
Masters of Science in Chemical Sciences
Department
Chemistry and Biochemistry
Committee Chair/First Advisor
Mohammad Halim
Second Advisor
Bharat Baruah
Third Advisor
Wei Zhou
Abstract
Chemical pesticides have detrimental effects on the ecosystem and human and animal health. Although pesticides are designed to control insects, rodents, fungi, and many other things, they are exposed to air, water, and soil. How pesticides degrade in the atmosphere, bind, and interact with biological systems received great attention to predict their adverse effects on the environment. In addition, the toxicological impact of pesticides including cancer risks and human mortality, highlights the need to fundamentally probe their binding behaviors with biological samples. To identify the gas phase breakdown products of two predominant pesticides such as glyphosate and propanil as they are widely used herbicides in the United States, in-source and collision-induced dissociation coupled with mass spectrometry were used. Furthermore, pesticides' effects on plasma proteins are investigated using mass spectrometry, molecular docking, and molecular dynamics. The heme-containing Cytochrome C, myoglobin, and non-heme-containing lysozyme protein were utilized as a model protein in this work to anticipate binding and interaction caused by glyphosate. When examining Cytochrome C in the presence of water, its mass spectrum exhibited a range of charge states from 5+ to 15+, with the 8+ state being the most prominent peak. Interestingly, at low glyphosate concentrations, the charge states of Cytochrome C significantly diminished, although no direct binding between glyphosate and the protein was observed. However, at higher concentrations (>25 micromolar) of glyphosate, Cytochrome C displayed the formation of glyphosate adducts ranging from one to nine, alongside binding with eight phosphate molecules. Conversely, when glyphosate was introduced to myoglobin, only adducts with magic numbers of four and eight glyphosates were detected, indicating a distinct interaction pattern. Furthermore, in the case of lysozyme, a non-heme-containing protein, interaction with glyphosate was observed, albeit primarily at very high concentrations, resulting in the formation of a series of four glyphosate adducts. Moreover, molecular docking and molecular dynamic simulation were performed to replicate the mass spectrometry experiment involving glyphosate and Cytochrome C. Our findings highlight a stronger affinity and interaction between glyphosate and phosphate molecules with heme-containing proteins, such as Cytochrome C and myoglobin, compared to non-heme-containing proteins like lysozyme.
Included in
Analytical Chemistry Commons, Computational Chemistry Commons, Environmental Chemistry Commons