자료유형  

 학위논문

Control Number  

0017164967

International Standard Book Number  

9798346389316

Dewey Decimal Classification Number  

545

Main Entry-Personal Name  

Huang, Kai-Hung.

Publication, Distribution, etc. (Imprint  

[S.l.] : Purdue University., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

385 p.

General Note  

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

General Note  

Advisor: Cooks, R. Graham.

Dissertation Note  

Thesis (Ph.D.)--Purdue University, 2024.

Summary, Etc.  

요약Mass spectrometry (MS) has long been recognized as a technology for bioanalysis. However, this thesis focuses on exploiting mass spectrometry for chemical reactions. The work described here covers the (a) investigation of chemistry at interfaces by MS, (b) utilization of MS to accelerate drug discovery processes, and (c) applications of MS techniques for organic synthesis. MS techniques are used to scrutinize the distinctive chemistry and super acidity mechanisms at the gas/liquid interfaces by reacting carbon dioxide (gas phase) with amines (solution, in droplets). The intriguing trace water effect in creating this unique environment at the interfaces is described. A systematic survey of reactions promoted by glass microspheres at liquid/solid interfaces is conducted, revealing that glass surface can act as strong base to speed up reactions. Additionally, the ability of glass surface to degrade biomolecules is revealed, which has implications for bioanalysis. Desorption electrospray ionization (DESI), an ambient ionization method, can be used as a rapid analytical technique for the direct analysis of complex reaction mixtures or bioassays without sample workup. Moreover, DESI can also be used as a small-scale synthetic tool due to accelerated reactions in generated microdroplets. These characteristics make DESI a core technology for high-throughput (HT) experimentation that prioritizes speed to achieve three major roles. (i) HT reaction screening leverages the reaction acceleration phenomenon for rapid chemical space exploration, especially for the late-stage diversification of drug molecules. The entire process, from sampling the reaction mixture by droplets to on-the-fly chemical transformation during millisecond timescales to analysis by MS, achieves an overall throughput of one reaction per second in an integrated fashion. Diverse chemical transformations for various functional groups were achieved, with over 10 4 reactions explored and over 10 3 analogs identified within three hours. (ii) HT synthesis is achieved using an automated homebuilt array-to-array transfer system. The synthetic system uses DESI microdroplets for transferring reaction mixtures from a precursor array to products on a product array. High conversions of diverse reactions with synthetic throughput of 0.2-0.02 Hz and scale of ng-µg (pmole-nmole) in a spatially resolved manner are demonstrated. Hundreds of modified bioactive molecules are generated in an array format, and the spatial distribution of the products is visualized by mass spectrometry imaging. (iii) HT bioassays are demonstrated by combining the label-free nature of MS with the high-speed analysis of DESI. The contactless feature, with high tolerance towards complex mixtures, allows direct bioassays with minimal sample preparation. An opioid receptor binding assay is described with an evaluation of the binding affinity of synthesized opioid analogs. An on-surface enzymatic assay is developed for measuring the bioactivity of deposited molecules in situ. The consolidation of (i) HT reaction screening, (ii) HT synthesis, and (iii) HT bioassays by a single but versatile technique, HT-DESI, can expedite the early drug discovery process. For applications, MS technologies are utilized to probe reactive intermediates and the reaction mechanisms of palladium-catalyzed coupling reactions. MS is also used to explore chemical reactions for natural products, rapidly generating analogs for bioactivity evaluation and benefiting bioanalysis through the discovery of derivatization reactions. HT tandem MS is demonstrated to be powerful for structural elucidation and reaction site identification.

Subject Added Entry-Topical Term  

Mass spectrometry.

Subject Added Entry-Topical Term  

Humidity.

Subject Added Entry-Topical Term  

Acids.

Subject Added Entry-Topical Term  

Gases.

Subject Added Entry-Topical Term  

Oxidation.

Subject Added Entry-Topical Term  

Reagents.

Subject Added Entry-Topical Term  

Chemical reactions.

Subject Added Entry-Topical Term  

Carbon dioxide.

Subject Added Entry-Topical Term  

Water.

Subject Added Entry-Topical Term  

Drugs.

Subject Added Entry-Topical Term  

Data processing.

Subject Added Entry-Topical Term  

Scientific imaging.

Subject Added Entry-Topical Term  

Phenols.

Subject Added Entry-Topical Term  

Narcotics.

Subject Added Entry-Topical Term  

Analytical chemistry.

Subject Added Entry-Topical Term  

Organic chemistry.

Subject Added Entry-Topical Term  

Pharmaceutical sciences.

Added Entry-Corporate Name  

Purdue University.

Host Item Entry  

Dissertations Abstracts International. 86-05B.

Electronic Location and Access  

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Control Number  

joongbu:653649