Synthesis of heterobimetallic gold(i) ferrocenyl-substituted 1, 2, 3-triazol-5-ylidene complexes as potential anticancer agents. Issue 45 (2nd October 2018)

• Record Type: Journal Article
• Authors: Aucamp, Danielle; Kumar, Sreedhar V.; Liles, David C.; Fernandes, Manuel A.; Harmse, Leonie; Bezuidenhout, Daniela I.
• Is Part Of: Dalton transactions. Volume 47:Issue 45(2018)
• Page Start: 16072
• Page End: 16081
• Publication Date: 2018-10-02
• Subjects: Chemistry, Inorganic -- Periodicals; Chemistry, Physical and theoretical -- Periodicals; Chemistry, Inorganic -- Periodicals; 546.05
• DOI: 10.1039/c8dt03116a
• Languages: English
• ISSNs: 1477-9226

Abstract

Abstract : Apoptotic cancer cell death mediated by a cationic gold(i ) phosphine complex bearing a ferrocenyl-functionalised mesoionic carbene. Abstract : 1, 2, 3-Triazol-5-ylidene (trz) complexes of gold(i ) containing a ferrocenyl substituent on the C4-position of the trz ring were synthesized to yield the neutral heterobimetallic gold(i ) trz chlorido (2 ), gold(i ) trz phenyl (3 ), and the cationic gold(i ) trz triphenylphospine (5 ) complexes. In order to compare the effect of silver(i ) as central metal vs. gold(i ), [Ag(trz)2 ] + (4 ) was also prepared, while variation of the C4-1, 2, 3-triazol-5-ylidene substituent from a ferrocenyl to a phenyl group was done to prepare the monometallic analogue of5, namely the cationic Au(i ) trz triphenylphosphine complex6 . The complexes were characterised with spectroscopic and electrochemical methods, and the single crystal X-ray structures of2–6 were determined. NMR stability studies of5 as a representative example of the series of complexes were performed to confirm the stability of the complexes in the solvent dimethylsulfoxide and in aqueous solution. The anti-cancer potential of5 was evaluated against the lung cancer cell lines A549 and H1975, and the human embryonic kidney cell line (HEK-293) was used as a non-cancer model. IC50 values of 0.89, 0.23 and 5.43 μM, respectively, were obtained for A549, H1975 and HEK-293, respectively, indicating the activity and selectivity of5 for cancer cells. Fluorescence microscopy experiments as a preliminary mode-of-action study evidenced an apoptotic cell death mechanism rather than necrotic cell death.