Bachelor with Honours Dissertations - open access

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https://hdl.handle.net/10292/14987
The "Bachelor with Honours Dissertations - open access" collection contains digital copies of AUT University B(Hons) dissertations approved for open access. B(Hons) dissertations are required to be open access from April 2022. Past students may contact the Tuwhera team (tuwhera.opentheses@aut.ac.nz) if they wish to make their B(Hons) open access.

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Browsing Bachelor with Honours Dissertations - open access by Author "Brasch, Nicola"

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    Synthesis and Antibiotic Activity of Vitamin B12-Vancomycin Conjugates
    (Auckland University of Technology, 2023) Stackpole, Ben; Brasch, Nicola; Seale, Brent
    Vitamin B12 has the potential to be used as a “Trojan horse” for drug delivery applications, with previously reported examples including anti-cancer drugs and antimicrobial drugs. As B12 is too large to cross cellular membranes by diffusion, humans and bacteria uptake it via active transport processes mediated by a series of proteins. Conjugating therapeutic molecules to B12 allows this process to be hijacked to transport cargo into cells. Because B12 is an essential nutrient and many species of bacteria cannot synthesise it themselves, this is a promising method for transporting antibiotics into bacteria. This may be especially useful in the case of Gram-negative bacteria, which possess an additional outer membrane that prevents many antibiotics from entering the cell. In this research project, we investigated the antibiotic activity of B12-vancomycin conjugates. Vancomycin is a glycopeptide antibiotic which inihibits bacterial cell wall synthesis. Due to its large size, it cannot diffuse across bacterial membranes and so it is only effective against Gram-positive bacteria. By conjugating vancomycin to B¬12, we hypothesised that it could be transported across the outer membrane of Gram-negative bacteria and inhibit their growth. Four different B12-vancomycin conjugates were successfully synthesised, differing in the linker used and the site of conjugation to B12. The conjugates were tested for antibiotic activity against Escherichia coli. None of the conjugates displayed antibiotic activity.
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    Synthesis and Properties of Cobalamin Derivatives Incorporating Halogenated Alkenyl Ligands
    (Auckland University of Technology, 2022) Maretic, Ema; Brasch, Nicola
    Synthesis of organocobalamins has been shown to be a complex process due to the conditions required to coordinate the organic molecules to the cobalt metal centre. It has been found that due to the light and air sensitive nature of typical organocobalamins, a strict air-free and dark environment is required to successfully synthesise the desired compounds. There is an abundance of literature reported on alkyl and alkynylcobalamins compared with alkenylcobalamins. The attempted synthesis of halogenated vinylcobalamins was conducted using two different methods to coordinate a halogenated alkenyl ligand to the cobalt metal centre of vitamin B12. The reduction method used sodium borohydride and a reverse addition of the reduced Co(I) species to the ligand resulted in several different complexes being produced. The final attempt of this method resulted in the formation of a new compound, shown by the new aromatic peaks observed in the 1H NMR spectrum. Unfortunately, this new compound was unable to be fully characterised due to decomposition, and the LC-MS results proved inconclusive. The reduction-free method used copper(I) acetate to remove the cyanide ligand from the beta axial site and a base, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), to deprotonate the trichloroethene ligand. In the final attempt of this method, it was found that a room temperature reaction for 4 hours resulted in the observation of several new compounds. The 1H NMR spectrum from this synthesis indicated a new major complex was present in the product mixture, with five new aromatic proton peaks (7.24 ppm, 6.85 ppm, 6.82 ppm, 6.25 ppm, and 6.05 ppm). However, once again LC-MS analysis of the product mixture was inconclusive.
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