Date of Award

Fall 2013

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

First Advisor

Alexander Wei

Committee Chair

Alexander Wei

Committee Member 1

David H. Thompson

Committee Member 2

Yu Xia

Committee Member 3

Mingji Dai

Abstract

Heparan sulfate is a complex cell-surface proteoglycan that serves many important roles in biology, such as growth and development, immune response and pathogenesis. Heparan sulfate is structurally heterogeneous due to the variable post- glycosylation modifications, particularly the generation of diverse sets of sulfate esters (sulfoforms) for any given disaccharide unit. In order to establish useful relationships between heparan sulfate structure and biological activity, a set of well-defined sulfoforms is necessary to support binding affinity screening. In this thesis, we describe the generation of diverse sulfoforms from heparan disaccharides using a fluorous tag to facilitate purification of highly charged intermediates, and their subsequent immobilizaion on substrates for affinity binding studies.

A library of heparan disaccharide sulfoforms was prepared from a single intermediate using an orthogonal protecting group system, to enable the controlled unmasking of hydroxyls or amines for subsequent sulfonation. A practical challenge of this approach is the need to carry highly polar intermediates through multiple synthetic steps. This was addressed by installing a perfluoroalkyl (fluorous) tag on the reducing end of the orthogonally protected disaccharide. The fluorous tag facilitated the separation of polar intermediates from non-fluorous byproducts via a two-stage solid-phase extraction. In this manner, a library of 1,4-linked disaccharides comprised of glucuronic acid (GlcA) and glucosamine (GlcN) could be prepared with a variable set of sulfonated substituents. The fluorous tag was retained on the final product to enable their non- covalent adhesion onto perfluoroalkyl-functionalized glass slides in microarray format, for biological screening against L-selectin, FGF2, and urokinase.

Lithium ion batteries have quickly become an important energy source and storage medium for electronics in recent years. Increasing the useful lifetime of batteries is a key challenge in their wide use. A number of perfluoroalkyl-functionalized small molecules were prepared as performance-enhancing additives for lithium ion batteries. Perfluorooctyl ethylene carbonate was identified as a candidate that had positive effects on both cell cycling and cell impedance.

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