Document Type

Dissertation - Open Access

Award Date

2023

Degree Name

Doctor of Philosophy (PhD)

Department / School

Chemistry and Biochemistry

First Advisor

Douglas Raynie

Keywords

Apoptosis, Cytotoxicity, Deep eutectic solvents, Green chemistry, Mammalian cell lines, Physicochemical properties

Abstract

In the past few years, there has been a notable surge in demand for high-purity medicines due to the prevalence of chronic diseases such as cancer, hypertension, diabetes, cardiovascular diseases, and neurological disorders. Considerable efforts have been dedicated to discovering new solvents that are environmentally friendly and cost-effective that are well-suited for industrial applications. Deep eutectic solvents have gained recognition as a highly promising alternative to organic solvents and ionic liquids due to their easily sourced raw materials, simple and cheap preparation methods, high tunability, low volatility, low toxicity, and biodegradability. The industrial utilization of deep eutectic solvents (DESs) is constrained by limited data on solvatochromic parameters, biodegradability, and toxicity, despite their impressive performance in various applications. Recent studies have questioned the initial perception of deep eutectic solvents (DESs) as "green solvents" due to their benign constituents. This study focused on conducting comprehensive investigations into the potential toxicity of carboxylic acid-based DESs on mammalian cell lines (HEK293, A549, and MDA-MB-231) as well as gaining a thorough understanding of the underlying mechanism through which DESs may pose harm to organisms. The carboxylic acid-based DESs were prepared by combining different molar ratios of hydrogen bond donors (butyric, pentanoic, and hexanoic acid) and hydrogen bond acceptor (acetylcholine chloride) to produce a eutectic mixture. Characterization techniques (NMR and FT-IR) were employed to determine the purity, molecular identity, and chemical bonding interactions between the hydrogen bond acceptor (HBA) and hydrogen bond donor (HBD) in the carboxylic acid-based DESs. UV-vis spectroscopy was employed to investigate the solvatochromic properties of the formulated DESs. The 1H NMR analysis indicated that all peaks observed in the spectra of the carboxylic acid-based deep eutectic solvents (DESs) corresponded to their constituent components, suggesting the absence of impurities. Furthermore, both 1H NMR and FTIR spectroscopy confirmed the presence of hydrogen bonding between the hydrogen bond acceptor (HBA) and the hydrogen bond donor (HBD) in the DESs. The findings from the study revealed that carboxylic acid-based deep eutectic solvents (DESs) exhibit solvatochromic properties that are similar in polarity to both organic solvents and ionic liquids which enhances their versatility and widens their range of potential applications in diverse fields. The results obtained from the MTT assay indicated that the cytotoxic potential of carboxylic acid-based DESs was cell-line dependent. The carboxylic acid-based DESs exhibited anti-cancer effects, and these effects were mediated through the inhibition of cell proliferation of the cancer cells. The findings from the western blotting assay revealed that no detection of activated Caspase-3 (an effector caspase that executes apoptosis) was observed in the carboxylic acid-based DESs. In summary, carboxylic acid-based DESs exhibit promising potential as anti-cancer agents and this outcome sets the stage for future research on carboxylic acid-based DESs in the realm of anti-cancer drug discovery.

Publisher

South Dakota State University

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Chemistry Commons

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Rights Statement

In Copyright