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Advancing the Chemical Understanding...

Fosnacht, Kaylin G. W.,

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Advancing the Chemical Understanding of Hydrogen Sulfide and Related Reactive Sulfur Species With Small Molecule Tools for Delivery and Sensing /

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Advancing the Chemical Understanding of Hydrogen Sulfide and Related Reactive Sulfur Species With Small Molecule Tools for Delivery and Sensing // Kaylin G. W Fosnacht.
作者:	Fosnacht, Kaylin G. W.,
面頁冊數:	1 electronic resource (612 pages)
附註:	Source: Dissertations Abstracts International, Volume: 86-05, Section: B.
Contained By:	Dissertations Abstracts International86-05B.
標題:	Chemistry. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31334374
ISBN:	9798342715638

Advancing the Chemical Understanding of Hydrogen Sulfide and Related Reactive Sulfur Species With Small Molecule Tools for Delivery and Sensing /
Fosnacht, Kaylin G. W.,

Advancing the Chemical Understanding of Hydrogen Sulfide and Related Reactive Sulfur Species With Small Molecule Tools for Delivery and Sensing /Kaylin G. W Fosnacht. - 1 electronic resource (612 pages)

Source: Dissertations Abstracts International, Volume: 86-05, Section: B.

Reactive sulfur species (RSS), such as thiols, polysulfides, hydrogen sulfide (H2S), and persulfides (RSSH), play essential roles in biological chemistry, including roles in redox homeostasis and small molecule signaling pathways. Previously known as a toxic gas, H2S was established as a gasotransmitter in the late 1990's and is defined as a membrane permeable small molecule that is endogenously produced and involved in specific cell signaling pathways. For this reason, the association of H2S imbalances with various diseases, such as Parkinson's disease, diabetes, and asthma, has been studied and changes in endogenous H2S are indicated as a potential disease biomarker. More recently, the importance of persulfides and other RSS in addition to H2S has become a major research focus due to their overlap in activity with H2S and newly discovered importance in biological processes. In particular, recent work has further clarified that many cellular signaling processes initially attributed to H2S are likely due to persulfides. Overall, understanding the RSS pool both fundamentally and also in biological systems is crucial. Carefully developed tools to both detect and deliver RSS are needed to further understand the rich chemistry of RSS within the body.Within this dissertation three main aims are addressed: (1) improved H2S sensing tools for longer duration studies, (2) donor molecules that release RSS, and (3) increasing fundamental understanding of persulfide reactivity. Chapter I is a comprehensive review of fluorescent probes of H2S and other RSS and includes discussion of the important advantages and limitations of each probe type. Chapter II features a cell-trappable H2S probe that provides a large, selective fluorescence turn-on to H2S and was used to sense H2S in live cells. Chapter III details a palette of thiol-activated H2S donors that also produce a fluorescent response in the blue to NIR emission wavelength range. Notably, the NIR donor was applied to live rats to image the fluorescence turn-on when subcutaneously delivered. Chapter IV describes the development of a small library of esterase-activated persulfide donors and kinetic analysis of persulfide release, donor side reactivity, and observed persulfide persistence. Chapter V is a combined computational and experimental analysis of persulfide reactivity with thiols where increasing steric bulk or electron withdrawal near the persulfide can shunt persulfide reactivity through the transpersulfidation pathway. Experimentally, we used a persulfide donor and persulfide trapping agent to monitor and measure transpersulfidation from a bulky penicillamine-based persulfide to a cysteine-based thiol, which is the first direct observation of transpersulfidation between low molecular weight species. This dissertation includes previously published co-authored material.

English

ISBN: 9798342715638Subjects--Topical Terms:

516420
Chemistry.
Subjects--Index Terms:

Chemical biology

Advancing the Chemical Understanding of Hydrogen Sulfide and Related Reactive Sulfur Species With Small Molecule Tools for Delivery and Sensing /
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