Gold(III)-dithiocarbamato complexes: antibacterial properties and encapsulation studies into Metal-Organic Frameworks (MOFs) for drug delivery
Klosowski, Sebastian
Klosowski, Sebastian
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2024-11-21
Type
master thesis
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Abstract
Previous research on gold(III)-dithiocarbamato complexes has shown in vivo cytotoxicity towards tumours 1-4 times greater than cisplatin, even in cisplatin resistant tumours and in addition, negligible nephrotoxicity (Adokoh, 2020). They have also been recently shown to have positive antibacterial and antibiofilm properties against multi-drug resistant strains (Ratia, et al, 2023). In this study an attempt was made in synthesising a number of gold(III) dithiocarbamato complexes via transmetallation from a previously synthesised zinc(II)- ethylestersarcosinedithiocarbamato intermediate in order to avoid formation of dimer impurities usually associated with a direct synthesis method. Secondly, the uptake of said complexes by a zinc(II) MOF was investigated due to its potential as a chemoselective drug delivery system. Lastly the antibacterial properties of the complexes were also studied both with and without blue light irradiation. The synthesis of two out of the three attempted compounds was successful, with NMR and IR spectroscopy data confirming their structures and lack of impurities. Neither of the two complexes synthesized could be taken up by the zinc(II) MOF, with no conclusive evidence to suggest the mechanism behind this negative result. A positive bactericidal effect was seen for both compounds with more efficacy towards gram negative S. aureus. The gold(III) complex containing an aromatic moiety has shown an increase in efficacy in the presence of blue light, an increase in ROS production in E. coli, but no significant impact on biofilm formation. The study concluded that transmetallation is successful at synthesising pure gold(III) dithiocarbamato complexes. More work needs to be done on elucidating the reason as to why the zinc(II) MOF does not take up the complexes, potentially by producing the framework in crystalline form in order to determine whether a change in its morphology occurs when the gold(III) complexes are introduced. Alternatively, an entirely new MOF should be trialled. A lot more work is required in terms of bactericidal properties of the complexes, particularly in elucidating their mechanism of action both with and without blue light. It would also be of interest to see whether the compounds are capable of antibiofilm effects with blue light exposure.
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University of Galway
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Attribution-NonCommercial-NoDerivatives 4.0 International