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.
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Chemistry
Committee Chair
Alexander Wei
Date of Award
Fall 2013
Recommended Citation
Casselman, Matthew Daniel, "Fluorous- Phase Synthesis of Heparan Sulfate Disaccharides & Low-Molecular Weight Additives for Enhancing the Performance of Lithium-Ion Batteries." (2013). Open Access Dissertations. 173.
https://docs.lib.purdue.edu/open_access_dissertations/173
First Advisor
Alexander Wei
Committee Member 1
David H. Thompson
Committee Member 2
Yu Xia
Committee Member 3
Mingji Dai