Emerging Therapeutics for Organophosphorus Nerve Agent Poisonings. The Development of a Fluoride Ion Battery System Utilizing Nanoparticles.

Emerging Therapeutics for Organophosphorus Nerve Agent Poisonings. The Development of a Fluoride Ion Battery System Utilizing Nanoparticles.

Bibliographic Details
Main Author: McKenney, Ryan Kenneth
Language:English
Published: The Ohio State University / OhioLINK 2017
Subjects:
Chemistry
Organophosphorus Nerve Agents
Treatments for Nerve Agents Exposures
Nanoparticles
Fluoride Ion Battery
Organic Chemistry
Cyclic Peptides
Organometallics
Acetylcholinesterase
Acetylcholine
Haptens
One-Bead-One-Compound Library
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=osu1491830263330328
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-osu14918302633303282021-08-03T07:01:32Z Emerging Therapeutics for Organophosphorus Nerve Agent Poisonings. The Development of a Fluoride Ion Battery System Utilizing Nanoparticles. McKenney, Ryan Kenneth Chemistry Organophosphorus Nerve Agents Treatments for Nerve Agents Exposures Nanoparticles Fluoride Ion Battery Organic Chemistry Cyclic Peptides Organometallics Acetylcholinesterase Acetylcholine Haptens One-Bead-One-Compound Library The purpose of this dissertation is to highlight three unique approaches towards discovering a catalytic treatment towards organophosphorus (OP) poisoning. All three potential approaches focus on developing catalytic treatment methods that focus on hydrolyzing OP nerve agents before they can inhibit acetylcholinesterase (AChE). AChE is a serine hydrolase which is responsible for hydrolyzing the neurotransmitter acetylcholine (ACh). AChE operates near diffusion control and can hydrolyze upwards of 25,000 ACh molecules every second. However, when AChE is inhibited by a nerve agent, an excess amount of ACh will build up at neurosynaptic gaps, thereby causing a cholinergic crisis. Once this occurs, a person will start to develop symptoms of muscle contractions, blurry vision, seizures and/or respiratory failure. An OP nerve agent has this effect because it is a structural analog to ACh; however, phosphylation of the active site is more difficult to reverse. Reactivation of AChE can occur by hydrolyzing the phosphylated enzyme with a nucleophile such as 2-PAM (often administered after OP exposure has occurred). Unfortunately, if this reactivation does not occur, the phosphylated enzyme will undergo a spontaneous dealkylation step (termed aging) to give a “dead” enzyme, which to date cannot be reactivated.The first therapeutic design focuses on the research and development of phosphorane haptens. These haptens are conjugated to some mutagen and administered into mice. This causes an immune response and can generate catalytic antibodies which are capable of hydrolyzing the nerve agent VX. In total, ten different haptens were synthesized, mimicking the hydrolysis transition state of VX, and all generated specific antibodies. Each titer of antibodies were then tested against authentic VX samples.The second approach focuses on the development of a combinatorial approach to synthesizing a random library of cyclic peptides. These cyclic peptides are meant to model the active site of enzymes such as OP hydrolase, which is capable of hydrolyzing a broad spectrum of OP compounds. Utilizing solid phase peptide synthesis will allow for a high-throughput screening of potential peptides against the catalytic hydrolysis of a model OP compound. The third approach will emphasize the synthesis and screening of organometallic compounds towards the hydrolysis of a variety of model OP and pesticide compounds. Different transition metals and ligands will be synthesized and submitted to a high throughput screening to determine their activity against OP mimics, including pesticide thions.Finally, the last chapter is a standalone project and will concentrate on the development of a fluoride ion battery (FIB) system. The FIB system described utilizes a novel electrolyte which is stable to the fluoride ion. This chapter will also highlight the new synthetic methods developed for nanoparticle synthesis. These nanoparticles will be used as the working electrode material in a fluoride ion battery. 2017-07-28 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1491830263330328 http://rave.ohiolink.edu/etdc/view?acc_num=osu1491830263330328 restricted--full text unavailable until 2022-05-08 This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Chemistry
Organophosphorus Nerve Agents
Treatments for Nerve Agents Exposures
Nanoparticles
Fluoride Ion Battery
Organic Chemistry
Cyclic Peptides
Organometallics
Acetylcholinesterase
Acetylcholine
Haptens
One-Bead-One-Compound Library
spellingShingle Chemistry
Organophosphorus Nerve Agents
Treatments for Nerve Agents Exposures
Nanoparticles
Fluoride Ion Battery
Organic Chemistry
Cyclic Peptides
Organometallics
Acetylcholinesterase
Acetylcholine
Haptens
One-Bead-One-Compound Library
McKenney, Ryan Kenneth
Emerging Therapeutics for Organophosphorus Nerve Agent Poisonings. The Development of a Fluoride Ion Battery System Utilizing Nanoparticles.
author McKenney, Ryan Kenneth
author_facet McKenney, Ryan Kenneth
author_sort McKenney, Ryan Kenneth
title Emerging Therapeutics for Organophosphorus Nerve Agent Poisonings. The Development of a Fluoride Ion Battery System Utilizing Nanoparticles.
title_short Emerging Therapeutics for Organophosphorus Nerve Agent Poisonings. The Development of a Fluoride Ion Battery System Utilizing Nanoparticles.
title_full Emerging Therapeutics for Organophosphorus Nerve Agent Poisonings. The Development of a Fluoride Ion Battery System Utilizing Nanoparticles.
title_fullStr Emerging Therapeutics for Organophosphorus Nerve Agent Poisonings. The Development of a Fluoride Ion Battery System Utilizing Nanoparticles.
title_full_unstemmed Emerging Therapeutics for Organophosphorus Nerve Agent Poisonings. The Development of a Fluoride Ion Battery System Utilizing Nanoparticles.
title_sort emerging therapeutics for organophosphorus nerve agent poisonings. the development of a fluoride ion battery system utilizing nanoparticles.
publisher The Ohio State University / OhioLINK
publishDate 2017
url http://rave.ohiolink.edu/etdc/view?acc_num=osu1491830263330328
work_keys_str_mv AT mckenneyryankenneth emergingtherapeuticsfororganophosphorusnerveagentpoisoningsthedevelopmentofafluorideionbatterysystemutilizingnanoparticles
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