Synthesis and Applications of Polysaccharide-Based Materials Using N-Thiocarboxyanhydrides and Polypeptides

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Virginia Tech


Polysaccharides and polypeptides are two types of biopolymers that are used in biomedical, industrial, and commercial applications. Both families of biopolymers are generally biodegradable, sustainable, and often exhibit low toxicity. Polysaccharides and polypeptides are polymers derived from natural resources and can be modified or synthesized through polymerization of various monomers. Polypeptides, specifically, are typically synthesized by polymerizing monomers such as N-carboxyanhydrides (NCAs) or N-thiocarboxyanhydrides (NTAs) to form homopolymers or random copolymers when using two different NCA/NTA monomers simultaneously. Chapter 1 begins with a background on polysaccharide and polypeptide-based materials with a focus on polysaccharide-block-polypeptide block copolymers. Previous work includes combining these two biopolymers through methods requiring post-polymerization purification. Chapter 1 introduces the field, challenges it faces, and how this work can help pose some solutions to these challenges. In this thesis, we utilized NTAs to synthesize polypeptides (Chapters 2 and 3) and as an H2S donor (Chapter 4). Combining polysaccharides and polypeptides into a block copolymer is useful for drug delivery and blend compatibilization applications. In Chapter 2, we synthesized a dextran-block-poly(benzyl glutamate) block copolymer that is amphiphilic; the differences in hydrophilicity among the two blocks allowed for nanostructures to form in situ in water, which we envision can be used for applications in drug delivery. Because nanostructures are formed in situ, this method negates the need for post-polymerization modification or purification, a requirement of many other nanostructure formation procedures. Coarse-grained molecular dynamics simulations were employed to shed light on interactions found on the molecular level. The interactions studied were then used to explain the nanostructures observed experimentally. In Chapter 3, we similarly formed another polysaccharide-block-polypeptide with the same poly(benzyl glutamate) polypeptide used in Chapter 2 but using ethyl cellulose for the polysaccharide. Poly(benzyl glutamate) is similar in structure to the commercial plastic polyethylene terephthalate (PET), a petroleum-based polymer that is not biodegradable. Therefore, this ethyl cellulose-block-poly(benzyl glutamate) BCP was used as compatibilizer to improve mixing in immiscible ethyl cellulose/PET blends. These blends afforded a more bio-derived alternative to PET/petroleum-based plastics. This chapter focuses on the synthetic efforts, a common challenge with polysaccharides, to produce this block copolymer as well as blend preparation and characterization. Chapter 4 utilizes an NTA as an H2S donor rather than a monomer for polymerization. H2S is an endogenous signaling gas that plays an important role in many organs and systems. In humans, H2S deficiency leads to a range of medical issues including hypertension, preeclampsia, liver diseases, and Alzheimer's disease. NTAs are advantageous for H2S delivery in the biomedical field due to their amino-acid origin and innocuous byproducts. The NTA donor in this work was attached to amylopectin via thiol-ene "click" photochemistry with the amino acid cysteine providing the thiol source on amylopectin. H2S release half-lives were in the range of several hours and depended on polymer molecular weight. Lastly, Chapter 5 summarizes the conclusions formed from these projects as well as potential future extensions from this work.



polypeptide, biopolymer, block copolymer, polymerization-induced self-assembly, N-thiocarboxyanhydride