Potential Therapeutic Applications of Cyclodextrin Host: Guest Interactions for the Remediation of Per and Polyfluoro Alkyl Substances from Biological Systems

Authors

Nawagamuwage Lilani Dilani Perera, Florida International UniversityFollow

Document Type

Dissertation

Degree

Doctor of Philosophy (PhD)

Major/Program

Chemistry

First Advisor's Name

Kevin E. O'Shea

First Advisor's Committee Title

Co-committee chair

Second Advisor's Name

Jaroslava Miksovska

Second Advisor's Committee Title

Co-committee chair

Third Advisor's Name

Francisco Alberto Fernandez-Lima

Third Advisor's Committee Title

Committee member

Fourth Advisor's Name

Prem Chapagain

Fourth Advisor's Committee Title

Committee member

Fifth Advisor's Name

James M. Quirke

Fifth Advisor's Committee Title

Committee member

Keywords

PFAS, Gen X, HSA, Tryptophan, Fluorescence, Absorbance, Hemoglobin, Cyclodextrin, Kinetics, 1, 8-ANS, Competitive binding

Date of Defense

10-10-2022

Abstract

This dissertation project focuses on the emerging per and perfluoroalkyl substances (PFAS) which are among the most problematic halogenated organic contaminants in the environment. PFAS causes serious health issues in humans and animals. Spectroscopic methods were used to probe the interactions between emerging PFAS and the biological proteins, human serum albumin (HSA), the most abundant protein in the blood plasma, and the hemoglobin (Hb) protein were chosen for this dissertation research study. Steady-state fluorescence emission studies, circular dichroism studies, NMR techniques, and competition studies with site specific binding fluorophores were employed to investigate the interactions between the selected PFAS and the biological proteins. A number of emerging PFAS were employed in an attempt to develop structure-activity relationships between protein bonding as a function of PFAS chain length and oxygen content. Results obtained from these studies illustrate the selected emerging PFAS strongly bind with both HSA and Hb proteins with association constants on the order of 102- 105 M-1. The binding of the PFAS results in structural and conformational changes to these two selected human proteins. With this determination of the sites and strengths of the PFAS binding to these proteins, we extended the study to explore the use of cyclodextrin to extract these PFAS from proteins as a potential strategy for PFAS remediation in biological systems. Therefore, in my dissertation, I have used cyclodextrin (CD) and its derivatives, which is a nontoxic, water-soluble compound that is safe for human consumption to develop a remediation method for emerging PFAS in biological systems which can eventually be developed as a therapeutic method to treat health issues cause by PFAS inside the human body. These dissertation projects suggest that the encapsulation of emerging PFAS by CDs has potential for PFAS remediation in biological systems.

Identifier

FIDC010868

Previously Published In

Perera, N.D., Miksovska, J. and O’Shea, K.E., 2022. Elucidation of specific binding sites and extraction of toxic Gen X from HSA employing cyclodextrin. Journal of Hazardous Materials, 425, p.127765

Recommended Citation

Perera, Nawagamuwage Lilani Dilani, "Potential Therapeutic Applications of Cyclodextrin Host: Guest Interactions for the Remediation of Per and Polyfluoro Alkyl Substances from Biological Systems" (2022). FIU Electronic Theses and Dissertations. 5210.
https://digitalcommons.fiu.edu/etd/5210