Synthesis of heterobimetallic gold(<scp>i</scp>) ferrocenyl-substituted 1,2,3-triazol-5-ylidene complexes as potential anticancer agents

Aucamp, Danielle; Kumar, Vellas Sreedhar; Liles, David C.; Fernandes, Manuel A.; Harmse, Leonie; Bezuidenhout, Daniela Ina

doi:10.1039/c8dt03116a

Cited by 35 publications

(17 citation statements)

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“…The carbene carbon signal is comparable to that reported for 3 a (δ C 176.0 ppm in C 6 D 6 ) and the mesityl analogue (δ C 175.8 ppm in C 6 D 6 ) [64] . The carbene resonances of previously reported N1,N3‐diarylated ferrocenyl substituted Au I complexes were within the range 160.9–183.1 ppm (CDCl 3 ) [60] . Crystals of 4 a were grown overnight from a concentrated CH 2 Cl 2 solution layered with pentane at −20 °C.…”

Section: Resultssupporting

confidence: 81%

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A Cytotoxic Bis(1,2,3‐triazol‐5‐ylidene)carbazolide Gold(III) Complex Targets DNA by Partial Intercalation

Westhuizen

Slabber

Fernandes

et al. 2021

Chemistry A European J

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The syntheses of bis(triazolium)carbazole precursors and their corresponding coinage metal (Au, Ag) complexes are reported. For alkylated triazolium salts, di‐ or tetranuclear complexes with bridging ligands were isolated, while the bis(aryl) analogue afforded a bis(carbene) AuI‐CNC pincer complex suitable for oxidation to the redox‐stable [AuIII(CNC)Cl]+ cation. Although the ligand salt and the [AuIII(CNC)Cl]+ complex were both notably cytotoxic toward the breast cancer cell line MDA‐MB‐231, the AuIII complex was somewhat more selective. Electrophoresis, viscometry, UV‐vis, CD and LD spectroscopy suggest the cytotoxic [AuIII(CNC)Cl]+ complex behaves as a partial DNA intercalator. In silico screening indicated that the [AuIII(CNC)Cl]+ complex can target DNA three‐way junctions with good specificity, several other regular B‐DNA forms, and Z‐DNA. Multiple hydrophobic π‐type interactions involving T and A bases appear to be important for B‐form DNA binding, while phosphate O⋅⋅⋅Au interactions evidently underpin Z‐DNA binding. The CNC ligand effectively stabilizes the AuIII ion, preventing reduction in the presence of glutathione. Both the redox stability and DNA affinity of the hit compound might be key factors underpinning its cytotoxicity in vitro.

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Section: Resultssupporting

confidence: 81%

“…For metallodrug design, 1,2,3‐triazol‐5‐ylidene (trz) ligands, which are a subclass of NHCs, offer facile modulation, high functional group tolerance, and stabilization of metals in both high‐ and low oxidation states [53–58] . Surprisingly, few reports address the anticancer potential of trz‐based compounds [59–62] …”

Section: Introductionmentioning

confidence: 99%

A Cytotoxic Bis(1,2,3‐triazol‐5‐ylidene)carbazolide Gold(III) Complex Targets DNA by Partial Intercalation

Westhuizen

Slabber

Fernandes

et al. 2021

Chemistry A European J

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“…To avoid this chloride abstraction mechanism (see above), a further MIC gold complex was synthesized with phenyl as the second ligand instead of chloride. Following a synthetic route introduced by Bertrand, Bezuidenhout, and co‐workers, [18a, i] the gold complex (PhDippTrz)AuPh was synthesized (Scheme 5). Recrystallizing in CH 2 Cl 2 /hexane resulted in the complex with 27 % yield.…”

Section: Resultsmentioning

confidence: 99%

Directed Design of a Au^I Complex with a Reduced Mesoionic Carbene Radical Ligand: Insights from 1,2,3‐Triazolylidene Selenium Adducts and Extensive Electrochemical Investigations

Beerhues

Neubrand

Sobottka

et al. 2021

Chemistry A European J

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Carbene‐based radicals are important for both fundamental and applied chemical research. Herein, extensive electrochemical investigations of nine different 1,2,3‐triazolylidene selenium adducts are reported. It is found that the half‐wave potentials of the first reduction of the selones correlate with their calculated LUMO levels and the LUMO levels of the corresponding triazolylidene‐based mesoionic carbenes (MICs). Furthermore, unexpected quasi‐reversibility of the reduction of two triazoline selones, exhibiting comparable reduction potentials, was discovered. Through UV/Vis/NIR and EPR spectroelectrochemical investigations supported by DFT calculations, the radical anion was unambiguously assigned to be triazoline centered. This electrochemical behavior was transferred to a triazolylidene‐type MIC‐gold phenyl complex resulting in a MIC‐radical coordinated AuI species. Apart from UV‐Vis‐NIR and EPR spectroelectrochemical investigations of the reduction, the reduced gold‐coordinated MIC radical complex was also formed in situ in the bulk through chemical reduction. This is the first report of a monodentate triazolylidene‐based MIC ligand that can be reduced to its anion radical in a metal complex. The results presented here provide design principles for stabilizing radicals based on MICs.

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“…The bond lengths within the triazolylidene ring, as well as the Au−C Carbene and Au−Cl bond lengths are all in the expected range (Table 2). [7a,8b,e,14a,21] The triazolylidene ring of 3 a is twisted with respect to the connected Cp‐ring with a dihedral angle of 38°. The angle between the phenyl substituent and the triazolylidene ring in 7 a and 7 b varies from 46 to 56°.…”

Section: Synthesis and Characterizationmentioning

confidence: 99%

Synthesis, Characterization, and Evaluation of Antibacterial Activity of Ferrocenyl‐1,2,3‐Triazoles, Triazolium Salts, and Triazolylidene Complexes of Gold(i) and Silver(i)

et al. 2021

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1,2,3-triazoles, the corresponding triazolium salts, and the resulting mesoionic carbenes (MICs) of the 1,2,3-triazol-5ylidene type are at the forefront of contemporary research. In this contribution, we present a comprehensive study involving eight triazoles, seventeen triazolium salts, two silver(i)-and four gold(i)-MIC complexes. The substituents on the N1-atom of the heterocycles are either ferrocenyl or phenyl and those on the C4-atom bear various alkyl groups. All the compounds were thoroughly characterized by a combination of multinuclear NMR spectroscopy, ESI-MS and in many cases through single crystal X-ray diffraction studies. In the electrochemical analysis, all ferrocenyl-containing compounds display a ferrocenyl-based oxidation step. Additionally, in both the triazolium salts, and the respective metal complexes, a ligand centered reduction step is observed. All the complexes were tested for their antibacterial properties against the Gram-negative bacterial strains Salmonella typhimurium (S. typhimurium) and Escherichia coli (E. coli). Many of the tested compounds display good antibacterial activity against the rather resistant Salmonella strain. To inhibit the growth of E. coli, higher concentrations of the compounds tested were required. A preliminary structureactivity relationship of this set of compounds is also reported.

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Synthesis of heterobimetallic gold(i) ferrocenyl-substituted 1,2,3-triazol-5-ylidene complexes as potential anticancer agents

Abstract: Apoptotic cancer cell death mediated by a cationic gold(i) phosphine complex bearing a ferrocenyl-functionalised mesoionic carbene.

Cited by 35 publications

References 50 publications

A Cytotoxic Bis(1,2,3‐triazol‐5‐ylidene)carbazolide Gold(III) Complex Targets DNA by Partial Intercalation

A Cytotoxic Bis(1,2,3‐triazol‐5‐ylidene)carbazolide Gold(III) Complex Targets DNA by Partial Intercalation

Directed Design of a Au^I Complex with a Reduced Mesoionic Carbene Radical Ligand: Insights from 1,2,3‐Triazolylidene Selenium Adducts and Extensive Electrochemical Investigations

Synthesis, Characterization, and Evaluation of Antibacterial Activity of Ferrocenyl‐1,2,3‐Triazoles, Triazolium Salts, and Triazolylidene Complexes of Gold(i) and Silver(i)

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Synthesis of heterobimetallic gold(i) ferrocenyl-substituted 1,2,3-triazol-5-ylidene complexes as potential anticancer agents

Abstract: Apoptotic cancer cell death mediated by a cationic gold(i) phosphine complex bearing a ferrocenyl-functionalised mesoionic carbene.

Cited by 35 publications

References 50 publications

A Cytotoxic Bis(1,2,3‐triazol‐5‐ylidene)carbazolide Gold(III) Complex Targets DNA by Partial Intercalation

A Cytotoxic Bis(1,2,3‐triazol‐5‐ylidene)carbazolide Gold(III) Complex Targets DNA by Partial Intercalation

Directed Design of a AuI Complex with a Reduced Mesoionic Carbene Radical Ligand: Insights from 1,2,3‐Triazolylidene Selenium Adducts and Extensive Electrochemical Investigations

Synthesis, Characterization, and Evaluation of Antibacterial Activity of Ferrocenyl‐1,2,3‐Triazoles, Triazolium Salts, and Triazolylidene Complexes of Gold(i) and Silver(i)

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Directed Design of a Au^I Complex with a Reduced Mesoionic Carbene Radical Ligand: Insights from 1,2,3‐Triazolylidene Selenium Adducts and Extensive Electrochemical Investigations