Author ORCID Identifier


Document Type


Date of Award


Degree Name

Doctor of Philosophy in Chemistry - (Ph.D.)


Chemistry and Environmental Science

First Advisor

Hao Chen

Second Advisor

Zeyuan Qiu

Third Advisor

Alexei Khalizov

Fourth Advisor

Yuanwei Zhang

Fifth Advisor

S. Basuray


Benefitting from its high detection sensitivity and specificity, mass spectrometry (MS) has become a powerful technique in academia and industry. The aim of this dissertation study is to develop new mass spectrometric methods for organic reaction screening, detection of oligosaccharide/glycan in complex matrices, and nitrosamine absolute quantitation.

First, an electrochemistry/mass spectrometry (EC/MS) platform is built to generate an N-cyclopropylaniline radical cation electrochemically and to monitor its reactivity toward alkenes, which leads to the discovery of a new redox neutral reaction of intermolecular [3 + 2] annulation of N-cyclopropylanilines and alkenes. Net redox neutral electrosynthesis is quite rare in synthetic organic electrochemistry. Taking full advantage of the online EC/MS platform as a screening tool which only uses 50 nmol of substrates, a large scale electrosynthesis for 4-chloro-N-(2-phenylcyclopentyl)aniline in 128 mg is successfully conducted in an electrochemical cell. Such an EC/MS screening of reaction may expedite the discovery of other novel redox neutral electrochemical reactions.

Second, conventional MS-based analytical methods for carbohydrates are time-consuming because of offline sample pretreatment to remove matrix which suppresses MS signal. A fast and sensitive MS-based oligosaccharide characterization strategy is developed, termed desalting paper spray mass spectrometry (DPS-MS), that uses a piece of triangular paper (10 mm x 5 mm, height x base) for both carbohydrate desalting and subsequent ionization for analysis of various oligosaccharide types of analytes in complex nonvolatile buffers (Tris-HC1, PBS, and HEPES), and glycosyltransferases (GT) reaction products. This new analytical method is not only fast (<5 min per sample) and straightforward but is also highly sensitive (LOD of 1.1 nM for β-cyclodextrin). Furthermore, DPS-MS quantitative analysis of acceptor sugars in GT reactions control samples afford a slight deviation (6.5%-11.6%) from theoretical values. This vital result shows excellent potential for onsite, high-throughput characterization of GT activities and carbohydrate diagnostics by DPS-MS.

Third, N-Nitrosamines, possible carcinogenic substrates, are recently found in the sartan family of drugs and led to drug recalls. Their detection and quantification are therefore of significant importance for human health. Although many literature quantitation papers reported, they focused on simple nitrosamines, relying on the use of standards. Nevertheless, quantitation of nitrosamines directly derived from drug molecules with a complicated structure is not explored, due to the grand challenge of lacking standards that are difficult and expensive to synthesize. A novel absolute quantitation approach for N-nitrosamines using coulometric mass spectrometry (CMS) based on Faraday's Law is explored. In this approach, reductive conversion of N-nitrosamines into electrochemically active hydrazines is accomplished using zinc as a reductant under acidic conditions and hydrazines are then easily quantified using CMS, without using standards.



To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.