Date

2015

Major

Chemistry (B.S.)

Document Type and Release Option

Thesis (open access)

Faculty Mentor

Dr. Hans-Joerg Schanz

Abstract

During a traumatic brain injury (TBI) sustained in combination with hemorrhagic shock the brain undergoes anoxic conditions resulting from swelling and blood loss. Traditional intravenous solutions are used to replace blood volume, but are unable to replace the blood’s oxygen carrying capacity. A proposed treatment based on isotonic solutions containing hemoglobin-based oxygen carriers (HBOC’s) which were intended to provide readily available oxygen was developed. However, cell-free hemoglobin was shown to have excessive oxidative potential. Polynitroxylated Pegylated Hemoglobin (PNPH) was developed to address this shortcoming. During PNPH synthesis a combination of polyethylene glycol (PEG) and (2,2,6,6-tetramethylpiperidin-1-yl)oxidanyl (TEMPO), is bound to the cysteine and lysine residues on the protein. The PEG serves as a physical buffer, slowing oxygen release, while the TEMPO converts released superoxide radicals and counteracts their adverse effects. This antioxidant capability allows PNPH’s to successfully serve in their role, however, the synthesis of PNPH’s remains labor and cost intensive. This research focuses on the development of a TEMPO and PEG containing copolymer which can be bound to cell-free hemoglobin to serve in the same antioxidant capacity with additional benefits. These benefits include: increased PEG and TEMPO loading capacity, optimizability in the ratio between PEG and TEMPO, and a potentially easier synthesis pathway. This document focuses on the development of TEMPO containing ring-opening metastasis polymerization compatible monomers as a component of the target polymer and TBI treatment.

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