Synthesis and cytotoxicity studies of novel NHC–Gold(I) pseudohalides and thiolates

Dada, Oyinlola; Curran, Danielle; O’Beirne, Cillian; Müller‐Bunz, Helge; Zhu, Xiangming; Tacke, Matthias

doi:10.1016/j.jorganchem.2017.03.050

Cited by 27 publications

(23 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Bond angles of 108.40(10)° for 12 , 109.44(8)° for 13 , and 108.83(12)° for 14 are observed for the Au–S–C(30) angle. These values are in good agreement with similar compounds reported earlier by the Tacke group [ 25 , 26 ].…”

Section: Resultssupporting

confidence: 93%

Synthesis and Cytotoxicity Studies of Novel NHC*-Gold(I) Complexes Derived from Lepidiline A

et al. 2018

Self Cite

View full text Add to dashboard Cite

Ten novel N-heterocyclic carbene gold(I) complexes derived from lepidiline A (1,3-dibenzyl-4,5-dimethylimidazolium chloride) are reported here with full characterisation and biological testing. (1,3-Dibenzyl-4,5-diphenylimidazol-2-ylidene)gold(I) chloride (NHC*-AuCl) (1) was modified by substituting the chloride for the following: cyanide (2), dithiocarbamates (3–5), p-mercaptobenzoate derivatives (12–14) and N-acetyl-l-cysteine derivatives (15–17). All complexes were synthesised in good yields of 57–78%. Complexes 2, 12, 13, and 14 were further characterised by X-ray crystallography. Initial evaluation of the biological activity was conducted on all ten complexes against the multidrug resistant MCF-7topo breast cancer, HCT-116wt, and p53 knockout mutant HCT-116−/− colon carcinoma cell lines. Across the three cell lines tested, mainly single-digit micromolar IC50 values were observed. Nanomolar activity was exhibited on the MCF-7topo cell line with 3 displaying an IC50 of 0.28 μM ± 0.03 μM. Complexes incorporating a Au–S bond resulted in higher cytotoxic activity when compared to complexes 1 and 2. Theoretical calculations, carried out at the MN15/6–311++G(2df,p) computational level, show that NHC* is the more favourable ligand for Au(I)-Cl when compared to PPh3.

show abstract

Section: Resultssupporting

confidence: 93%

Synthesis and Cytotoxicity Studies of Novel NHC*-Gold(I) Complexes Derived from Lepidiline A

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“… 7 , 12 − 14 In particular, (NHC)Au I X and related complexes came into the focus of medicinal chemists and were examined for their suitability as chemotherapeutic agents. 6 , 9 , 15 − 19 The straightforward synthesis of the NHC ligands, the possibility of fine-tuning the physicochemical properties, and the reactivity of the resulting (NHC) gold(I) complexes make the latter to attractive lead structures for the development of novel metal-based drugs.…”

Section: Introductionmentioning

confidence: 99%

N-Heterocyclic Carbene Gold(I) Complexes: Mechanism of the Ligand Scrambling Reaction and Their Oxidation to Gold(III) in Aqueous Solutions

et al. 2020

View full text Add to dashboard Cite

N -Heterocyclic carbene (NHC) gold(I) complexes offer great prospects in medicinal chemistry as antiproliferative, anticancer, and antibacterial agents. However, further development requires a thorough understanding of their reaction behavior in aqueous media. Herein, we report the conversion of the bromido[3-ethyl-4-(4-methoxyphenyl)-5-(2-methoxypyridin-5-yl)-1-propylimidazol-2-ylidene]gold(I) ((NHC)Au I Br, 1 ) complex in acetonitrile/water mixtures to the bis[3-ethyl-4-(4-methoxyphenyl)-5-(2-methoxypyridin-5-yl)-1-propylimidazol-2-ylidene]gold(I) ([(NHC) 2 Au I ] + , 7 ), which is subsequently oxidized to the dibromidobis[3-ethyl-4-(4-methoxyphenyl)-5-(2-methoxypyridin-5-yl)-1-propylimidazol-2-ylidene]gold(III) ([(NHC) 2 Au III Br 2 ] + , 9 ). By combining experimental data from HPLC, NMR, and (LC-)/HR-MS with computational results from DFT calculations, we outline a detailed ligand scrambling reaction mechanism. The key step is the formation of the stacked ((NHC)Au I Br) 2 dimer ( 2 ) that rearranges to the T-shaped intermediate Br(NHC) 2 Au I –Au I Br ( 3 ). The dissociation of Br – from 3 and recombination lead to (NHC) 2 Au I –Au I Br 2 ( 5 ) followed by the separation into [(NHC) 2 Au I ] + ( 7 ) and [Au I Br 2 ] − ( 8 ). [Au I Br 2 ] − is not stable in an aqueous environment and degrades in an internal redox reaction to Au 0 and Br 2 . The latter in turn oxidizes 7 to the gold(III) species 9 . The reported ligand rearrangement of the (NHC)Au I Br complex differs from that found for related silver(I) analogous. A detailed understanding of this scrambling mechanism is of utmost importance for the interpretation of their biological activity and will help to further optimize them for biomedical and other applications.

show abstract

“…NHC*-Ag-OAc (SBC3) (Patil et al, 2011;Streciwilk et al, 2014;, which combine synthesis from a commercially available precursor (4,5-diphenylimidazole) with high antimicrobial activity in vitro (Sharkey et al, 2012) and in vivo (Browne et al 2014). In the homologue gold series, the introduction of pseudohalide anions led to stable and bioactive compounds (Dada et al, 2017). In this context, the attempted syntheses of the analogous NHC*-Ag I and -Cu I thio-and selenocyanates as potential antimicrobial species led to unexpected results with the formation of bis[bis(1,3-dibenzyl-4,5-diphenylimidazol-2ylidene)silver(I)] tris(thiocyanato)argentate(I) diethyl ether disolvate, (1), bis(-1,3-dibenzyl-4,5-diphenyl-2-selenoimidazole-2 Se:Se)bis[bromido(1,3-dibenzyl-4,5-diphenyl-2-selenoimidazole-Se)silver(I)] dichloromethane hexasolvate, (2), and catena-poly [[[(1,3-dibenzyl-4,5-diphenyl-2-selenoimidazole-Se)copper(I)]--cyanido-2 C:N] acetonitrile monosolvate], {[Cu(CN)(C 29 H 24 N 2 Se)]ÁC 2 H 3 N} n or NHC*Se-CuCNÁCH 3 CN, (3), the crystal structures of which are reported in this communication.…”

Section: Chemical Contextmentioning

confidence: 99%

Unexpected reactions of NHC*—Cu^I and —Ag^I bromides with potassium thio- or selenocyanate

Tacke¹,

Marhöfer²,

Althani³

et al. 2019

Acta Cryst E

Self Cite

View full text Add to dashboard Cite

show abstract

Synthesis and cytotoxicity studies of novel NHC–Gold(I) pseudohalides and thiolates

Cited by 27 publications

References 26 publications

Synthesis and Cytotoxicity Studies of Novel NHC*-Gold(I) Complexes Derived from Lepidiline A

Synthesis and Cytotoxicity Studies of Novel NHC*-Gold(I) Complexes Derived from Lepidiline A

N-Heterocyclic Carbene Gold(I) Complexes: Mechanism of the Ligand Scrambling Reaction and Their Oxidation to Gold(III) in Aqueous Solutions

Unexpected reactions of NHC*—Cu^I and —Ag^I bromides with potassium thio- or selenocyanate

Contact Info

Product

Resources

About

Synthesis and cytotoxicity studies of novel NHC–Gold(I) pseudohalides and thiolates

Cited by 27 publications

References 26 publications

Synthesis and Cytotoxicity Studies of Novel NHC*-Gold(I) Complexes Derived from Lepidiline A

Synthesis and Cytotoxicity Studies of Novel NHC*-Gold(I) Complexes Derived from Lepidiline A

N-Heterocyclic Carbene Gold(I) Complexes: Mechanism of the Ligand Scrambling Reaction and Their Oxidation to Gold(III) in Aqueous Solutions

Unexpected reactions of NHC*—CuI and —AgI bromides with potassium thio- or selenocyanate

Contact Info

Product

Resources

About

Unexpected reactions of NHC*—Cu^I and —Ag^I bromides with potassium thio- or selenocyanate