Identifier

etd-07082016-143208

Degree

Doctor of Philosophy (PhD)

Department

Chemistry

Document Type

Dissertation

Abstract

The objective of this work is to develop a new synthetic strategy for synthesizing advanced functional polypeptides or polypeptides in general. Polypeptides are amino acids based polymers with appealing properties for different applications. One of the key challenges in polypeptide research is the synthesis of functional polypeptides under mild conditions. We developed a system based on ring-opening polymerization (ROP) of N-thiocarboxyanhydrosulfides (NTAs) to synthesize polypeptides with wide range of molecular weights under mild conditions. Owing to NTAs’ good stability, our system serves as an excellent alternative to the traditional ROP of N-carboxyanhydrides (NCA). In Chapter 1, the fundamental knowledge and the cutting-edge research of polypeptides will be reviewed. The focus of the work in Chapter 2 is to develop a new class of functional polypeptide in traditional method via ROP of NCAs. This class of polypeptides combines several desired attributes for biomedical applications, which include: clickable pendant side chains for further functionalization, good water solubility, non-ionic nature to avoid unspecific interactions in biological systems, and unique secondary conformations (e.g. α-helix, β-sheet). In Chapter 3, I developed the first system to prepare polypeptides with controlled molecular weight via primary amine initiated solid-phase ring-opening polymerization (sROP) of NTAs under mild conditions in open air. Model NTA (e.g. BLG NTA, LYS NTA) monomers were synthesized for the first time, and were found to possess better thermal and moisture stability as compared to NCA analogs. The sROP proceeds by a normal amine mechanism as evidenced by matrix assisted light desorption ionization time of flight mass spectroscopy (MALDI-TOF MS). The controlled polymerization behavior of sROP is the direct result of high local monomer concentration in the solid phase, thus allowing for faster polymerization under relatively mild conditions. The work in Chapter 4 focuses on the development of solution phase polymerization of NTAs with TMG/benzoic acid as co-initiation system. PBLG with high molecular weights (33.6 kg/mol - 66.7 kg/mol) and narrow molecular weight distribution (PDI < 1.12) can be readily prepared with this system. The mechanism of the TMG/benzoic acid mediated ROP of NTAs is proposed to be activated monomer mechanism (AMM).

Date

2016

Document Availability at the Time of Submission

Secure the entire work for patent and/or proprietary purposes for a period of one year. Student has submitted appropriate documentation which states: During this period the copyright owner also agrees not to exercise her/his ownership rights, including public use in works, without prior authorization from LSU. At the end of the one year period, either we or LSU may request an automatic extension for one additional year. At the end of the one year secure period (or its extension, if such is requested), the work will be released for access worldwide.

Committee Chair

Zhang, Donghui

Included in

Chemistry Commons

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