Carbene-metal complexes as anticancer and antibacterial drug candidates
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|Title:||Carbene-metal complexes as anticancer and antibacterial drug candidates||Authors:||Hackenberg, Frauke Marie||Advisor:||Tacke, Matthias||Permanent link:||http://hdl.handle.net/10197/6783||Date:||2013||Online since:||2015-08-12T08:54:28Z||Abstract:||Within this project, novel silver(I)-, ruthenium(II)- and gold(I)-NHC complexes have been synthesised by the formation of appropriately substituted (benz)imidazolium and 4,5-diaryl-imidazolium halides followed by either metallation with silver acetate, or metallation with silver oxide followed by transmetallation with dichloro ruthenium (<italic>p</italic>-cymene) dimer or dimethylsulfido gold chloride. The three obtained NHC-gold(I) chlorides were further functionalised by reacting them with silver acetate or 2,3,4,6-tetra-<italic>O</italic>-benzyl-1-thio-β-D-glucopyranose to give NHC-gold(I) acetates or NHC-gold(I) thioglucopyranoses, respectively.All complexes were characterised by NMR (<super>1</super>H and <super>13</super>C), IR, microanalysis and MS. Melting points were determined for all complexes with the exception of (benz)imidazol-2-ylidene silver(I) acetates. The <italic>in vitro</italic> antibacterial activity against bacterial strains of <italic>E. coli</italic> and <italic>MRSA</italic> of all NHC-Ag(I)OAc complexes has been investigated utilizing the Kirby-Bauer disk diffusion method. <italic>In vitro</italic> MTT-based cytotoxicity assays against the human renal cancer cell line Caki-1 were carried out on all complexes and additionally against the human breast cancer cell line MCF-7 on all 4,5-diaryl-NHC silver(I) acetate as well as on all Ru(II)-NHC and Au(I)-NHC complexes. Lowest IC<sub>50</sub> values down to 0.51 (± 0.07) μM against Caki-1 and 1.4 (± 0.1) μM against MCF-7 have been found for the most promising NHC-silver(I) acetate complex 1,3-di(<italic>p</italic>-methylbenzyl)-4,5-di(<italic>p</italic>-methylphenyl)imidazol-2-ylidene silver(I) acetate, which is currently under further investigation. Moreover, after identifying Ag(I)-NHC lead structures and subsequently transmetallating them to their ruthenium- and gold-derivatives, four promising Ru(II)-NHC and Au(I)-NHC derivatives have been discovered.||Type of material:||Doctoral Thesis||Publisher:||University College Dublin. School of Chemistry and Chemical Biology||Qualification Name:||Ph.D.||Copyright (published version):||2013 the author||Keywords:||Antibacterial; Cytotoxicity; Gold; N-heterocyclic carbenes; Silver; Transition metals||Other versions:||http://dissertations.umi.com/ucd:10001||Language:||en||Status of Item:||Peer reviewed|
|Appears in Collections:||Chemistry Theses|
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