Synthesis, characterization and biological activity of bis[3-ethyl-4-aryl-5-(2-methoxypyridin-5-yl)-1-propyl-1,3-dihydro-2<i>H</i>-imidazol-2-ylidene]gold(<scp>i</scp>) complexes

Gallati, Caroline Marie; Goetzfried, Sina Katharina; Ortmeier, Anna; Sagasser, Jessica; Wurst, Klaus; Hermann, Martin; Baecker, Daniel; Kircher, Brigitte; Gust, Ronald

doi:10.1039/d0dt03902k

“…In previous papers, we reported on the design and in vitro activity of bromido[3-ethyl-4-aryl-5-(2-methoxypyridin-5-yl)-1-propyl-1,3dihydro-2H-imidazol-2-ylidene]gold(I) complexes and related [(NHC) 2 Au(I)] + species. [39][40] The latter caused significantly higher antiproliferative effects (IC 50 values  0.5 µM) than their (NHC)Au(I)Br counterparts (IC 50 = 3-6 µM). This finding is of particular importance, because the (NHC)Au(I)Br complexes undergo ligand rearrangement reactions to the related [(NHC) 2 Au(I)] + derivatives in the presence of water.…”

Section: Introductionmentioning

confidence: 98%

Investigations of the reactivity, stability and biological activity of halido (NHC)gold(i) complexes

Goetzfried

¹

,

Kapitza

²

,

Gallati

³

et al. 2022

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“…For this reason, ligands with biological interest have been chosen to achieve an effective interaction with gold atom. Hence, thiolate [31,32], dithiocarbamate [33,34], phosphine [35,36], or N-heterocyclic carbene [20,[37][38][39][40] ligands, among others, have been at the center of study in the last two decades, showing good biological results (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

“…For this reas ligands with biological interest have been chosen to achieve an effective interaction w gold atom. Hence, thiolate [31,32], dithiocarbamate [33,34], phosphine [35,36], or N-het ocyclic carbene [20,[37][38][39][40] ligands, among others, have been at the center of study in last two decades, showing good biological results (Figure 1). On the other hand, Ag(I) complexes have also been widely used as antimicrobial [ and anti-inflammatory [42] agents and have also received special attention for their an tumor activity [26,[43][44][45][46][47].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of New Thiourea-Metal Complexes with Promising Anticancer Properties

Canudo-Barreras

¹

,

Ortego

²

,

Izaga

³

et al. 2021

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In this work, two thiourea ligands bearing a phosphine group in one arm and in the other a phenyl group (T2) or 3,5-di-CF3 substituted phenyl ring (T1) have been prepared and their coordination to Au and Ag has been studied. A different behavior is observed for gold complexes, a linear geometry with coordination only to the phosphorus atom or an equilibrium between the linear and three-coordinated species is present, whereas for silver complexes the coordination of the ligand as P^S chelate is found. The thiourea ligands and their complexes were explored against different cancer cell lines (HeLa, A549, and Jurkat). The thiourea ligands do not exhibit relevant cytotoxicity in the tested cell lines and the coordination of a metal triggers excellent cytotoxic values in all cases. In general, data showed that gold complexes are more cytotoxic than the silver compounds with T1, in particular the complexes [AuT1(PPh3)]OTf, the bis(thiourea) [Au(T1)2]OTf and the gold-thiolate species [Au(SR)T1]. In contrast, with T2 better results are obtained with silver species [AgT1(PPh3)]OTf and the [Ag(T1)2]OTf. The role played by the ancillary ligand bound to the metal is important since it strongly affects the cytotoxic activity, being the bis(thiourea) complex the most active species. This study demonstrates that metal complexes derived from thiourea can be biologically active and these compounds are promising leads for further development as potential anticancer agents.

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“…The data are important for the interpretation of the in vitro results since 1a – 9a exhibited antiproliferative activity in ovarian cancer and leukemia cell lines at low micromolar concentrations, 41 whereas 1b – 9b caused these effects already at nanomolar concentrations. 42 Therefore, it is of interest to know more about the conditions for the transformation of 1a – 9a to the higher active 1b – 9b . Furthermore, the reaction with chloride is pivotal because of the high concentration in the cell culture medium, which leads to the formation of (NHC)Au I Cl complexes.…”

Section: Introductionmentioning

confidence: 99%

Internal and External Influences on Stability and Ligand Exchange Reactions in Bromido[3-ethyl-4-aryl-5-(2-methoxypyridin-5-yl)-1-propyl-1,3-dihydro-2H-imidazol-2-ylidene]gold(I) Complexes

Goetzfried

¹

,

Koenig

²

,

Gallati

³

et al. 2021

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The ligand scrambling reaction of gold(I) complexes is a phenomenon occurring primarily in L–Au I –X (L = phosphine, N -heterocyclic carbene (NHC), and thiol; X = halide and thiol) complexes and has been observed among others for e.g., the bromido[3-ethyl-4-(4-methoxyphenyl)-5-(2-methoxypyridin-5-yl)-1-propyl-1,3-dihydro-2 H -imidazol-2-ylidene]gold(I) complex ( 7a ), which underwent ligand rearrangement in aqueous solutions. In this study, we investigated the influence of substituents on the 4-aryl ring of the related (NHC)Au I Br complexes ( 1a – 9a ) in terms of the conversion to the [(NHC) 2 Au I ] + ( 1b – 9b ) and [(NHC) 2 Au III Br 2 ] + ( 1c – 9c ) species. Furthermore, the influence of external factors such as solvent, temperature, concentration, and presence of halides (Cl – , Br – , and I – ) or hydroxyl ions was studied to gain a deeper understanding of the ligand rearrangement reaction. The substituent on the 4-aryl ring has a marginal impact on the scrambling reaction. Out of the investigated organic solvents (dimethylformamide (DMF), dimethyl sulfoxide (DMSO), ethanol (EtOH), methanol (MeOH), and acetonitrile (ACN)), only ACN separates single complex molecules. In all other solvents, relatively stable ((NHC)Au I Br) 2 dimers are present. The addition of water to ACN solutions forces the formation of such dimeric units, starting the transformation to [(NHC) 2 Au I ] + and [(NHC) 2 Au III Br 2 ] + . The rate-determining step is the release of Br – from a T-shape intermediate because an excess of KBr terminates this reaction. Furthermore, it is obvious that only single molecules react with halides. The aurophilic interactions between two (NHC)Au I Br molecules are too strong in the presence of water and largely impeded reaction with halides. As a single molecule, the reaction with Cl – (e.g., in a 0.9% NaCl solution) is notable, while I – even leads to a fast and quantitative conversion to (NHC)Au I I and finally to [(NHC) 2 Au I ] + .

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Synthesis, characterization and biological activity of bis[3-ethyl-4-aryl-5-(2-methoxypyridin-5-yl)-1-propyl-1,3-dihydro-2H-imidazol-2-ylidene]gold(i) complexes

Cited by 10 publications

References 52 publications

Investigations of the reactivity, stability and biological activity of halido (NHC)gold(i) complexes

Investigations of the reactivity, stability and biological activity of halido (NHC)gold(i) complexes

Synthesis of New Thiourea-Metal Complexes with Promising Anticancer Properties

Internal and External Influences on Stability and Ligand Exchange Reactions in Bromido[3-ethyl-4-aryl-5-(2-methoxypyridin-5-yl)-1-propyl-1,3-dihydro-2H-imidazol-2-ylidene]gold(I) Complexes

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