From betaines to anionic N-heterocyclic carbenes. Borane, gold, rhodium, and nickel complexes starting from an imidazoliumphenolate and its carbene tautomer.
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PROVIDER: S-EPMC5238575 | BioStudies |
REPOSITORIES: biostudies
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Project description:Ferrocene containing <i>N</i>-heterocyclic carbene (NHC) ligated gold(I) complexes of the type [Au(NHC)<sub>2</sub>]<sup>+</sup> were prepared and found to be capable of regulating the formation of reactive oxygen species (ROS) via multiple mechanisms. Single crystal X-ray analysis of bis(1-(ferrocenylmethyl)-3-mesitylimidazol-2-ylidene)-gold(I) chloride (<b>5</b>) and bis(1,3-di(ferrocenylmethyl)imidazol-2-ylidene)-gold(I) chloride (<b>6</b>) revealed a quasi-liner geometry around the gold(I) centers, (i.e., the C<b>-</b>Au<b>-</b>C bond angle were measured to be ~177° and all the Au<b>-</b>C<sub>carbene</sub> bonds distances were in the range of 2.00 (7) - 2.03 (1) Å). A series of cell studies indicated that cell proliferation inhibition and ROS generation were directly proportional to amount of ferrocene contained within the [Au(NHC)<sub>2</sub>]<sup>+</sup> complexes (IC<sub>50</sub> of <b>6 < 5 <</b> bis(1-benzyl-3-mesitylimidazol-2-ylidene)-gold(I) chloride (<b>4</b>)). Complexes <b>4</b>-<b>6</b> were also confirmed to inhibit thioredoxin reductase as inferred from lipoate reduction assays and increase chelatable intracellular zinc concentrations. RNA microarray gene expression assays revealed that <b>6</b> induces endoplasmic reticulum stress response pathways as a result of ROS increase.
| S-EPMC4762604 | BioStudies
Project description:The ligand scrambling reaction of gold(I) complexes is a phenomenon occurring primarily in L-Au<sup>I</sup>-X (L = phosphine, <i>N</i>-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<i>H</i>-imidazol-2-ylidene]gold(I) complex (<b>7a</b>), 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<sup>I</sup>Br complexes (<b>1a</b>-<b>9a</b>) in terms of the conversion to the [(NHC)<sub>2</sub>Au<sup>I</sup>]<sup>+</sup> (<b>1b</b>-<b>9b</b>) and [(NHC)<sub>2</sub>Au<sup>III</sup>Br<sub>2</sub>]<sup>+</sup> (<b>1c</b>-<b>9c</b>) species. Furthermore, the influence of external factors such as solvent, temperature, concentration, and presence of halides (Cl<sup>-</sup>, Br<sup>-</sup>, and I<sup>-</sup>) 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<sup>I</sup>Br)<sub>2</sub> dimers are present. The addition of water to ACN solutions forces the formation of such dimeric units, starting the transformation to [(NHC)<sub>2</sub>Au<sup>I</sup>]<sup>+</sup> and [(NHC)<sub>2</sub>Au<sup>III</sup>Br<sub>2</sub>]<sup>+</sup>. The rate-determining step is the release of Br<sup>-</sup> 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<sup>I</sup>Br molecules are too strong in the presence of water and largely impeded reaction with halides. As a single molecule, the reaction with Cl<sup>-</sup> (e.g., in a 0.9% NaCl solution) is notable, while I<sup>-</sup> even leads to a fast and quantitative conversion to (NHC)Au<sup>I</sup>I and finally to [(NHC)<sub>2</sub>Au<sup>I</sup>]<sup>+</sup>.
| S-EPMC8277168 | BioStudies
Project description:The synthesis of heterobimetallic complexes remains a synthetic challenge in the field of organometallic chemistry. A possible approach in this regard might be the use of a bidentate heteroditopic bis(carbene) ligand that combines an imidazol-2-ylidene (<i>n</i>NHC) with a 1,2,3-triazol-5-ylidene (<i>tz</i>NHC) connected by an organic spacer. The optimized strategy to heterobimetallic complexes with this type of ligand involves a 3-step procedure: (i) Coordination of the <i>n</i>NHC, functionalized with a 1,2,3-triazole ring, to a metal center; (ii) formation of the triazolium ring by alkylation of the triazole N-3; (iii) deprotonation of the <i>tz</i>NHC precursor and coordination of the second metal center. Following this procedure, a novel Au(I)-Ag(I) dinuclear complex was isolated and its properties were compared to the analogous homobimetallic Ag(I)-Ag(I) and Au(I)-Au(I) complexes. The study was completed by the determination of the molecular structures of some synthetic intermediates.
| S-EPMC6631958 | BioStudies
Project description:The coordination ability of the [(ppy)Au(IPr)]<sup>2+</sup> fragment [ppy = 2-phenylpyridine, IPr = 1,3-<i>bis</i>(2,6-di-isopropylphenyl)-imidazol-2-ylidene] towards different anionic and neutral X ligands (X = Cl<sup>-</sup>, BF<sub>4</sub><sup>-</sup>, OTf<sup>-</sup>, H<sub>2</sub>O, 2-butyne, 3-hexyne) commonly involved in the crucial pre-equilibrium step of the alkyne hydration reaction is computationally investigated to shed light on unexpected experimental observations on its catalytic activity. Experiment reveals that BF<sub>4</sub><sup>-</sup> and OTf<sup>-</sup> have very similar coordination ability towards [(ppy)Au(IPr)]<sup>2+</sup> and slightly less than water, whereas the alkyne complex could not be observed in solution at least at the NMR sensitivity. Due to the steric hindrance/dispersion interaction balance between X and IPr, the [(ppy)Au(IPr)]<sup>2+</sup> fragment is computationally found to be much less selective than a model [(ppy)Au(NHC)]<sup>2+</sup> (NHC = 1,3-dimethylimidazol-2-ylidene) fragment towards the different ligands, in particular OTf<sup>-</sup> and BF<sub>4</sub><sup>-</sup>, in agreement with experiment. Effect of the ancillary ligand substitution demonstrates that the coordination ability of Au(III) is quantitatively strongly affected by the nature of the ligands (even more than the net charge of the complex) and that all the investigated gold fragments coordinate to alkynes more strongly than H<sub>2</sub>O. Remarkably, a stabilization of the water-coordinating species with respect to the alkyne-coordinating one can only be achieved within a microsolvation model, which reconciles theory with experiment. All the results reported here suggest that both the Au(III) fragment coordination ability and its proper computational modelling in the experimental conditions are fundamental issues for the design of efficient catalysts.
| S-EPMC8122707 | BioStudies
Project description:Copper-alumanyl complexes, [LCu-Al(SiN<sup>Dipp</sup> )], where L=carbene=NHC<sup>iPr</sup> (N,N'-diisopropyl-4,5-dimethyl-2-ylidene) and <sup>Me2</sup> CAAC (1-(2,6-diisopropylphenyl)-3,3,5,5-tetramethyl-pyrrolidin-2-ylidene) and featuring unsupported Al-Cu bonds, have been prepared. Divergent reactivity observed with carbodiimides and CO<sub>2</sub> implies an ambiphilicity in the Cu-Al interaction that is dependent on the identity of the carbene co-ligand.
| S-EPMC8252794 | BioStudies
Project description:To achieve a systems-based approach to targeting the antioxidant pathway, 1,4-naphthoquinone annulated N-heterocyclic carbene (NHC) [bis(1,3-dimesityl-4,5-naphthoquino-imidazol-2-ylidene)-gold(i)] [silver(i) dichloride] (<b>1</b>), [bis(1,3-dimesityl-4,5-naphthoquino-imidazol-2-ylidene)-gold(i)] chloride (<b>2</b>), and 1,3-dimesityl-4,5-naphthoquino-imidazol-2-ylidene)-gold(i) chloride (<b>3</b>)) were designed, synthesized, and tested for biological activity in a series of human cancer cell lines. The solution phase of complexes <b>1-3</b> were assigned using several spectroscopy techniques, including NMR spectroscopic analysis. Complexes <b>1</b> and <b>3</b> were further characterized by single crystal X-ray diffraction analysis. Electrochemical and spectroelectrochemical studies revealed that quinone reductions are reversible and that the electrochemically generated semiquinone and quinone dianions are stable under these conditions. Complex <b>1</b>, containing two NHC-quinone moieties (to accentuate exogenous ROS <i>via</i> redox cycling) centered around a Au(i) center (to inactivate thioredoxin reductase (TrxR) irreversibly), was found to inhibit cancer cell proliferation to a much greater extent than the individual components (<i>i.e.</i>, Au(i)-NHC alone or naphthoquinone alone). Treatment of A549 lung cancer cells with <b>1</b> produced a 27-fold increase in exogenous reactive oxygen species (ROS) which was found to localize to the mitochondria. The inhibition of TrxR, an essential mediator of ROS homeostasis, was achieved in the same cell line at low administrated concentrations of <b>1</b>. TrxR inhibition by <b>1</b> was similar to that of auranofin, a gold(i) containing complex known to inhibit TrxR irreversibly. Complex <b>1</b> was found to induce cell death <i>via</i> an apoptotic mechanism as confirmed by annexin-V staining. Complex <b>1</b> was demonstrated to be efficacious in zebrafish bearing A549 xenografts. These results provide support for the suggestion that a dual targeting approach that involves reducing ROS tolerance while concurrently increasing ROS production can perturb antioxidant homeostasis, enhance cancer cell death <i>in vitro</i>, and reduce tumor burden <i>in vivo</i>, as inferred from preliminary zebra fish model studies.
| S-EPMC5859730 | BioStudies
Project description:N-Heterocyclic carbene gold(I) complexes derived from 1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene (NHC*) represent a promising class of anticancer drugs. Complexes of the type NHC*-Au-L (L = Br-, I-, C?C-R) and [NHC*-Au-L]+ (L = NHC*, PPh3) have been synthesised. The X-ray crystal structures of all gold(I) complexes are presented; aurophilic interactions were observed in five of the complexes. The anticancer activity was assessed via MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)-based proliferation assays against the human colon carcinoma cell line HCT-116wt and the multidrug-resistant human breast carcinoma cell line MCF-7topo. Most complexes showed good cytotoxicity with IC50 values in the low micromolar range, while excellent sub-micromolar activity was observed for 2c, 3a and 3b. Generally, the activity of the ligands studied was as follows: carbene > phosphine > alkyne > halide, with an exception for the highly active iodido derivative 2c.
| S-EPMC7436326 | BioStudies
Project description:Acetic acid promotes the reduction of aldehydes and ketones by the readily available N-heterocyclic carbene borane, 1,3-dimethylimidazol-2-ylidene borane. Aldehydes are reduced over 1-24 h at room temperature with 1 equiv of acetic acid and 0.5 equiv of the NHC-borane. Ketone reductions are slower but can be accelerated by using 5 equiv of acetic acid. Aldehydes can be selectively reduced in the presence of ketones. On a small scale, products are isolated by evaporation of the reaction mixture and direct chromatography.
| S-EPMC3629027 | BioStudies
Project description:The bicyclic amido-substituted silicon(I) ring compound Si<sub>4</sub> {N(SiMe<sub>3</sub> )Mes}<sub>4</sub> 2 (Mes=Mesityl=2,4,6-Me<sub>3</sub> C<sub>6</sub> H<sub>2</sub> ) features enhanced zwitterionic character and different reactivity from the analogous compound Si<sub>4</sub> {N(SiMe<sub>3</sub> )Dipp}<sub>4</sub> 1 (Dipp=2,6-<sup>i</sup> Pr<sub>2</sub> C<sub>6</sub> H<sub>3</sub> ) due to the smaller mesityl substituents. In a reaction with the N-heterocyclic carbene NHC Me4 (1,3,4,5-tetramethyl-imidazol-2-ylidene), we observe adduct formation to give Si<sub>4</sub> {N(SiMe<sub>3</sub> )Mes}<sub>4</sub> ⋅ NHC Me4 (3). This adduct reacts further with the Lewis acid BH<sub>3</sub> to yield the Lewis acid-base complex Si<sub>4</sub> {N(SiMe<sub>3</sub> )Mes}<sub>4</sub> ⋅ NHC Me4 ⋅ BH<sub>3</sub> (4). Coordination of AlBr<sub>3</sub> to 2 leads to the adduct 5. Calculated proton affinities and fluoride ion affinities reveal highly Lewis basic and very weak Lewis acidic character of the low-valent silicon atoms in 1 and 2. This is confirmed by protonation of 1 and 2 with Brookharts acid yielding 6 and 7. Reaction with diphenylacetylene only occurs at 111 °C with 2 in toluene and is accompanied by fragmentation of 2 to afford the silacyclopropene 8 and the trisilanorbornadiene species 9.
| S-EPMC9297995 | BioStudies
Project description:Indenyl (Ind) rhodium N-heterocyclic carbene (NHC) complexes [Rh(η<sup>5</sup> -Ind)(NHC)(L)] were synthesised for 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene (SIPr) with L=C<sub>2</sub> H<sub>4</sub> (1), CO (2 a) and cyclooctene (COE; 3), for 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene (SIMes) with L=CO (2 b) and COE (4), and 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (IMes) with L=CO (2 c) and COE (5). Reaction of SIPr with [Rh(Cp*)(C<sub>2</sub> H<sub>4</sub> )<sub>2</sub> ] did not give the desired SIPr complex, thus demonstrating the "indenyl effect" in the synthesis of 1. Oxidative addition of HSi(OEt)<sub>3</sub> to 3 proceeded under mild conditions to give the Rh silyl hydride complex [Rh(Ind){Si(OEt)<sub>3</sub> }(H)(SIPr)] (6) with loss of COE. Tethered-fluorenyl NHC rhodium complexes [Rh{(η<sup>5</sup> -C<sub>13</sub> H<sub>8</sub> )C<sub>2</sub> H<sub>4</sub> N(C)C<sub>2</sub> H<sub>x</sub> NR}(L)] (x=4, R=Dipp, L=C<sub>2</sub> H<sub>4</sub> : 11; L=COE: 12; L=CO: 13; R=Mes, L=COE: 14; L=CO: 15; x=2, R=Me, L=COE: 16; L=CO: 17) were synthesised in low yields (5-31 %) in comparison to good yields for the monodentate complexes (49-79 %). Compounds 3 and 1, which contain labile alkene ligands, were successful catalysts for the catalytic borylation of benzene with B<sub>2</sub> pin<sub>2</sub> (Bpin=pinacolboronate, 97 and 93 % PhBpin respectively with 5 mol % catalyst, 24 h, 80 °C), with SIPr giving a more active catalyst than SIMes or IMes. Fluorenyl-tethered NHC complexes were much less active as borylation catalysts, and the carbonyl complexes were inactive. The borylation of toluene, biphenyl, anisole and diphenyl ether proceeded to give meta substitutions as the major product, with smaller amounts of para substitution and almost no ortho product. The borylation of octane and decane with B<sub>2</sub> pin<sub>2</sub> at 120 and 140 °C, respectively, was monitored by <sup>11</sup> B NMR spectroscopy, which showed high conversions into octyl and decylBpin over 4-7 days, thus demonstrating catalysed sp<sup>3</sup> C-H borylation with new piano stool rhodium indenyl complexes. Irradiation of the monodentate complexes with 400 or 420 nm light confirmed the ready dissociation of C<sub>2</sub> H<sub>4</sub> and COE ligands, whereas CO complexes were inert. Evidence for C-H bond activation in the alkyl groups of the NHC ligands was obtained.
| S-EPMC9299238 | BioStudies