ORCID Identifier(s)

ORCID 0000-0003-0460-0102

Graduation Semester and Year

Fall 2024

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Chemistry

Department

Chemistry and Biochemistry

First Advisor

Daniel W. Armstrong

Second Advisor

Kevin A. Schug

Third Advisor

Sherri A. McFarland

Fourth Advisor

Joseph A. Buonomo

Abstract

Separation science is a rapidly evolving field, where routine analyses are now done at speeds and efficiencies not thought to be possible several years ago. The tangential field of green analytical chemistry is evolving at an even faster rate and can be considered to be in its infancy stage. As green analytical chemistry is better understood, the greenness of a method will be considered during standard method development just as resolution, sensitivity, and efficiency are considered now. The first portion of this dissertation focuses on the development of mathematical and pragmatic methods to minimize the analytical method greenness score, and the introduction of unusual eluents. The analytical method greenness score was refined to consider instrument cycle time and was made a function of flow rate. Using the first order optimality condition, this function was minimized to solve for the greenest flow rate for any given separation. The derived expressions were used to compare the greenness of enantioseparations in the liquid phase to those in the supercritical fluid continuum. Two unusual eluents were proposed, the first being based on carbonated water or carbonated alcoholic water solutions. A simple delivery system was introduced that can carbonate a given mobile phase, to form carbonic acid and exploit the benefits of organic acid containing mobile phases. The second unusual eluent is a senary solvent system produced by balancing a mixture of carbon dioxide, methanol, acetonitrile, water, trifluoroacetic acid, and triethylamine. Using this eluent and a functionalized cyclofructan chiral stationary phase, the enantioseparation of Ru(II) and Os(II) polypyridyl complexes was achieved. This chapter represents one of the first examples of chiral separations of ionic compounds in a mobile phase that is primarily (>50% by volume) carbon dioxide. The greenness of separations produced by small volume columns packed with small (2.7 µm) superficially porous silica particles was demonstrated. These columns produce high efficiency and low volume peaks, which require them to be operated on small dispersion LC systems for optimal performance. The second portion of this dissertation focuses on extra-column effects and digital signal processing in modern LC to empower highly efficient and greener separations. The extra-column band broadening for nine different liquid chromatography systems was discussed including a variety of optical (UV, CD, and ELSD) and mass spectrometric (QqQ, and Orbitrap) detectors. It was shown that extra-column effects are particularly pronounced for microbore columns (1.0 mm) that are typically used for LC-MS “omics.” The mathematical removal of extra-column effects was examined, and the use of Tikhonov regularization with the Perona-Malik filter was introduced for the first time to produce artifact free “column-only” chromatograms. Finally, the removal of exponential tailing in chiral chromatography was investigated. This resolution enhancement technique was achieved using noise suppressed first derivatives produced through penalized least squares filtering and central difference numerical differentiation. The theory, methods, and applications presented in this dissertation will assist in achieving the next generation of sustainable separations.

Keywords

Green Separations, Enantiomeric Analysis, Chiral Separations, Deconvolution, Extra-Column Effects, Supercritical Fluids

Disciplines

Analytical Chemistry

License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Available for download on Thursday, June 12, 2025

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