Ruthenium N-heterocyclic Carbene Research Articles

Cationic abnormal N-heterocyclic carbene ruthenium complexes as suitable precursors for the synthesis of heterobimetallic compounds.

The cationic abnormal N-heterocyclic carbene complex [Ru(OAc)(dppe)(PC)]Br (2b) (PC = bidentate phosphine-carbene ligand) has been obtained by treatment of the neutral derivative RuBr(OAc)(PPh3)(PC) (2a) with dppe in THF. Reaction of 2b with Ag2O afforded the heterobimetallic complex Ru(OAc)(dppe)(PC)AgBr (2c) which can be easily transmetallated with [Ir(cod)Cl]2 giving Ru(OAc)(dppe)(PC)IrCl(cod) (2d). Similarly, [{Ru(OAc)(PC)(PC')}2Ag][AgBr2] (1b) reacts with [Ir(cod)Cl]2 with formation of Ru(OAc)(PC)(PC')IrCl(cod) (1e). All complexes were characterized by NMR in solution and by single crystal X-ray diffraction studies in solid state. For the cationic complexes the 1H NMR resonance of the carbene-proton is considerably down-field shifted (δ > 9 ppm) with respect to that of the neutral derivatives. Cyclic voltammetry and differential pulse voltammetry studies show that the Ru-centered redox process occurs at lower potential (ΔE > 100 mV) after transmetallation with iridium, suggesting an interaction of the two metals along the π-system of the heterocycle ligand. These complexes display catalytic activity in transfer hydrogenation of acetophenone in 2-propanol with a significant influence of Ir and Ag centers on the Ru moiety. The synthesis of the imidazolyl-based N-heterocyclic dicarbene Ru-Ir complexes, which entails the easy metallation of the reactive cationic abnormal N-heterocyclic carbene Ru complexes with Ag2O, represents a suitable pathway for the preparation of heterometallic ruthenium complexes.

A Ruthenium(II) N-Heterocyclic Carbene (NHC) Complex with Naphthalimide Ligand Triggers Apoptosis in Colorectal Cancer Cells via Activating the ROS-p38 MAPK Pathway.

The p38 MAPK pathway is known to influence the anti-tumor effects of several chemotherapeutics, including that of organometallic drugs. Previous studies have demonstrated the important role of p38 both as a regulator and a sensor of cellular reactive oxygen species (ROS) levels. Investigating the anti-cancer properties of novel 1,8-naphthalimide derivatives containing Rh(I) and Ru(II) N-heterocyclic carbene (NHC) ligands, we observed a profound induction of ROS by the complexes, which is most likely generated from mitochondria (mtROS). Further analyses revealed a rapid and consistent activation of p38 signaling by the naphthalimide-NHC conjugates, with the Ru(II) analogue—termed MC6—showing the strongest effect. In view of this, genetic as well as pharmacological inhibition of p38α, attenuated the anti-proliferative and pro-apoptotic effects of MC6 in HCT116 colon cancer cells, highlighting the involvement of this signaling molecule in the compound’s toxicity. Furthermore, the influence of MC6 on p38 signaling appeared to be dependent on ROS levels as treatment with general- and mitochondria-targeted anti-oxidants abrogated p38 activation in response to MC6 as well as the molecule’s cytotoxic- and apoptogenic response in HCT116 cells. Altogether, our results provide new insight into the molecular mechanisms of naphthalimide-metal NHC analogues via the ROS-induced activation of p38 MAPK, which may have therapeutic interest for the treatment of various cancer types.

Protonated water-soluble N-heterocyclic carbene ruthenium(II) complexes: Synthesis, cytotoxic and DNA binding properties and molecular docking study

New benzimidazolium salts 1a-d having methylpyridine group on the side chain, have been synthesized and reacted with Ag2O to produce Ag(I)-N-heterocyclic carbene (NHC) complexes 2a-d. Ag(I)-N-heterocyclic carbene (NHC) complexes were used as a carben transfer agents to synthesize water-soluble ruthenium(II)-NHC complexes 4a-d. All synthesized compounds were fully characterized by 1H and 13C NMR and HRMS spectroscopic techniques. Anticancer potential and IC50 values of ruthenium(II)-NHC complexes were evaluated by MTT assay against human colorectal cancer (Caco-2) and breast cancer (MCF-7) cell lines. The IC50 value of water-soluble ruthenium(II)-NHC complex 4d demonstrated remarkable cytotoxic activity against Caco-2 (18.0 ± 1) and MCF-7 (23.8 ± 0.5) cell lines. Also, 4d has better DNA binding capacity than 4a-c. DS 2017 R2 was used to exert molecular docking for understanding interactions between the water-soluble ruthenium(II)-NHC complexes and DNA. These complexes have been highlighted as a new type of drug.

Investigation of potential hybrid capacitor property of chelated N-Heterocyclic carbene Ruthenium(II) complex

The synthesis of chelated ruthenium(II) complex type Ru(η6-HMB) (NHC)Cl (NHC=N-heterocyclic carbene, HMB = hexamethylbenzene) is presented. The ruthenium(II)-NHC complex 6 was obtained in good yield and was fully characterised by NMR spectroscopy, X-ray diffraction and HRMS analysis. Electrochemical analysis by cyclic voltammetry (CV) revealed reversible redox behaviour at the ruthenium centre in 6. DFT studies and the catalytic activity of complex 6 on transfer hydrogenation reaction of aryl ketones are also presented. The potential hybrid capacitor applications of Ru-NHC complex is discussed and reported firstly in the literature. It was found that the highest performance was found at 20.1 F/g, which is a promising result for energy storage applications.

Enhanced Tumor Diagnostic and Therapeutic Effect of Mesoporous Silica Nanoparticle-Mediated Pre-targeted Strategy.

Improving the targeting efficiency of imaging agents or anticancer drugs has become essential in the current primary mission to enhance the diagnostic or therapeutic effects. To improve the tumor diagnosis and therapy effect, a promising drug-delivery and targeting strategy was established based on the bioorthogonal chemistry. The delivery system was composed of the pre-targeting carrier Biotin-MSNs-DBCO nanoparticles and the azido cargoes. The fluorescence probe 1-(3-azidopropyl) fluorescein (FITC-N3) and ruthenium N-heterocyclic carbene complex N3-S-S-NHC-Ru were synthesized and served as the tumor imaging and therapy probes, respectively. The cell imaging and viability was investigated by the Biotin-MSNs-DBCO pre-targeted for 4h in colonic carcinoma (HeLa) cells. For the tumor cell imaging, Biotin-MSNs-DBCO could react with FITC-N3 rapidly and completely in 20min with 93% yields. The fluorescence intensity of tumor cells was obviously increased by the Biotin-MSNs-DBCO pre-targeted. The cytotoxicity of the ruthenium complex N3-S-S-NHC-Ru was significantly improved appropriately three times with the IC50 (half inhibitory concentration) value of 6.68 ± 1.29μM and enhancement of the mitochondrial dysfunction. The pre-targeting nanoparticle Biotin-MSNs-DBCO could selectively capture the azido compounds in tumor cells, which provided a site-specific target for the cargoes and then resulted in an enhancement of diagnostic or therapeutic effects.

Deactivation of a ruthenium(II) N-heterocyclic carbene p-cymene complex during transfer hydrogenation catalysis

A ruthenium (II) N-heterocyclic carbene (NHC) complex was synthesized to investigate ligand dissociation as a possible deactivation pathway for the catalytic cycle of a transfer hydrogenation reaction. Diiodo(1,3-dimethylbenzimidazole-2-ylidene)(p-cymene)ruthenium(II) was synthesized for use as the catalytic species and characterized using physico-chemical, spectroscopic methods, and single crystal X-ray diffraction. The transfer of hydrogen from isopropanol to acetophenone was followed using 1H NMR. We observed 94% conversion of the substrate to the alcohol product after 1 h. We also found that the p-cymene complex decomposed during the catalytic reaction to the extent of 80% deactivation after 1 h, based on 1H NMR spectrometry. From Gaussian calculations, an ultraviolet–visible spectrum that is in excellent agreement with the actual spectrum was computed, giving insight into the nature of the absorptions observed experimentally.

Ruthenium(II) Bipyridyl Complexes with Cyclometalated NHC Ligands.

We present the synthesis and characterization of novel cyclometalated ruthenium N-heterocyclic carbene (NHC) complexes of the general formula [Ru(C^C*)(bpy)2]PF6 (bpy = 2,2'-bipyridine), with the C^C* ligand being based on different 1-phenylimidazoles. They were synthesized in a one-pot procedure starting from the corresponding p-cymene NHC complexes [Ru(C^C*)(p-cymene)Cl]. Their structural, spectroscopic, and electrochemical properties were investigated by NMR, X-ray, UV/vis, and CV, as well as density functional theory methods. Because of the stronger electron-donating carbene ligands, these complexes represent a new class of bisheteroleptic dyes with improved photophysical and electrochemical properties.

Transfer Hydrogenation from Glycerol: Activity and Recyclability of Iridium and Ruthenium Sulfonate-Functionalized N-Heterocyclic Carbene Catalysts

Three ruthenium(II) and two iridium(III) N-heterocyclic carbene (NHC) complexes functionalized with sulfonates are compared with respect to their activity and selectivity for the transfer hydrogenation of imines, aldehydes, ketones, and olefins using neat glycerol as hydrogen donor and solvent. Four of the five catalysts likely proceed through a monohydride mechanism and are more active for transfer hydrogenation of imines than aldehydes, ketones, and olefins. The fifth catalyst likely proceeds through a dihydride mechanism and is found to be more active for carbonyls than imines and olefins. Lactic acid is observed as the only detectable byproduct from glycerol. Quantitative poisoning experiments with 1,10-phenanthroline suggest that the predominant catalytically active species is a ligated homogeneous complex with weak binding to the poison. The potential for catalyst recycling is explored: the ruthenium NHC catalysts with chelating ligands are found to be more robust and recyclable relative to the irid...

Hydrodefluorination of Fluoroaromatics by Isopropyl Alcohol Catalyzed by a Ruthenium NHC Complex. An Unusual Role of the Carbene Ligand

The NHC (NHC = N-heterocyclic carbene) complex Cp*(IPr)RuH3 catalyzes hydrodefluorination of aromatic fluorides at 70 °C with isopropyl alcohol as the reducing reagent. The reaction is selective for aromatic fluorides, as almost negligible C(sp3)–F bond reduction takes place. The activity decreases from more to less fluorinated substrates, but polyaromatic monofluorides, such as 1-fluoronaphthalene and 6-fluoro-2-methylquinoline, can also be reduced in moderate to good yields. Kinetic studies are consistent with a mechanism based on elimination of NHC and reversible substrate coordination, followed by coordination of the alcohol.

Ruthenium(II) DMSO complexes with CˆC* cyclometalated phenylimidazol NHC ligands

We present the synthesis of cyclometalated ruthenium N-heterocyclic carbene (NHC) complexes of the general formula [Ru(CˆC*)(DMSO)3Cl] and their use as starting material for the synthesis of a heteroleptic 2,2′-bipyridine (bpy) complex [Ru(bpy)(CˆC*)(DMSO)Cl]. Starting from the corresponding η6-(p-cymene) complexes [Ru(p-cymene)(CˆC*)Cl], the π-coordinated aryl ligand is substituted by three S-bound dimethyl sulfoxide ligands. In the course of this substitution, the complexes undergo a change in geometry from facial to meridional, which is unambiguously proven by solid state structure determination and DFT calculations. The labile DMSO ligands can be substituted by bidentate ligands as shown for the widely used 2,2′-bipyridine. The resulting air- and moisture-stable heteroleptic complex features two bidentate (CˆC* + bpy) and two monodentate (Cl− + DMSO) ligands.

Dehydrogenative Synthesis of Carboxylic Acids from Primary Alcohols and Hydroxide Catalyzed by a Ruthenium N-Heterocyclic Carbene Complex.

Primary alcohols have been reacted with hydroxide and the ruthenium complex [RuCl2(IiPr)(p-cymene)] to afford carboxylic acids and dihydrogen. The dehydrogenative reaction is performed in toluene, which allows for a simple isolation of the products by precipitation and extraction. The transformation can be applied to a range of benzylic and saturated aliphatic alcohols containing halide and (thio)ether substituents, while olefins and ester groups are not compatible with the reaction conditions. Benzylic alcohols undergo faster conversion than other substrates, and a competing Cannizzaro reaction is most likely involved in this case. The kinetic isotope effect was determined to be 0.67 using 1-butanol as the substrate. A plausible catalytic cycle was characterized by DFT/B3LYP-D3 and involved coordination of the alcohol to the metal, β-hydride elimination, hydroxide attack on the coordinated aldehyde, and a second β-hydride elimination to furnish the carboxylate.

Mixed heteropentadienyl and N-heterocyclic carbene ruthenium(II) complexes: Synthesis and transfer hydrogenation catalysis

Two synthetic methodologies for obtaining novel mixed heteropentadienyl and N-heterocyclic carbenes (NHC) ruthenium(II) complexes have been explored. A synthetic strategy involving the addition of heteropentadienyl precursors to [RuII]-NHC complexes proved to be a successful route for the isolation of four novel mixed ligand complexes, namely stereoisomers [(p-cymene)RuII(BuImMe)(η3-exo-syn-CH2CHCHCHO)]BF4 (3 and 3′, BuImMe = 1-butyl-3-methylimidazolyl-2-idene) and [(η1-CH2CHCRCHSO2)RuII(PyImMe)(CH3CN)3](A) (PyImMe = 3-methyl-1-(2-pyridyl)imidazolyl-2-idene, R = H, A = BF4, 6; R = CH3, A = PF6, 7). Moreover complex 6 has been characterised by X-ray crystallography confirming the sulphur-bound monodentate nature of CH2CHCHCHSO2 ligand adopting an S-conformation. Complexes 6 and 7 were tested as pre-catalysts in the transfer hydrogenation reaction of benzophenone, showing moderate and good activities, respectively.

Synthesis and catalytic activity of supported acenaphthoimidazolylidene N-heterocyclic carbene ruthenium complex for ring closing metathesis (RCM) and ring opening metathesis polymerization (ROMP)

Ruthenium catalyzed ring closing metathesis (RCM) and ring opening metathesis polymerization (ROMP) reactions using a supported bis(arylimino)acenaphthene N-heterocyclic carbene (BIAN-NHC) complex have been reported. The BIAN-NHC Ru-complex exhibits excellent catalytic activity and tolerates a wide range of substrates at low catalyst loadings. DFT calculations were also carried out on some selected key intermediates in the reaction mechanism to study the effect of having the conjugated aromatic moiety (BIAN-NHC) in the backbone of the complex. The newly synthesized BIAN-NHC Ru-complex shows comparable catalytic activities to the commercially available second generation Ru catalyst HG2. The recycled complex was reused for up to eight reaction cycles for the RCM of N,N-diallyl tosylamine affording a high average isolated yield, with lower levels of Ru contamination in the final product.▪

Isolation of [Ru(IPr)2(CO)H]+ (IPr = 1,3-Bis(2,6-diisopropylphenyl)imidazol-2-ylidene) and Reactivity toward E–H (E = H, B) Bonds

Halide abstraction from the ruthenium N-heterocyclic carbene complex Ru(IPr)2(CO)HCl (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) with NaBAr4F (BAr4F = B{C6H3(3,5-CF3)2}4) gave the salt [Ru(IPr)2(CO)H]BAr4F (2), which was shown through a combined X-ray/neutron structure refinement and quantum theory of atoms in molecules (QTAIM) study to contain a bifurcated Ru···η3-H2C ξ-agostic interaction involving one iPr substituent of the IPr ligand. This system complements the previously reported [Ru(IMes)2(CO)H]+ cation (IMes =1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene), where a non-agostic form is favored. Treatment of 2 with CO, H2, and the amine–boranes H3B·NR2H (R = Me, H) gave [Ru(IPr)2(CO)3H]BAr4F (3), [Ru(IPr)2(CO)(η2-H2)H]BAr4F (4), and [Ru(IPr)2(CO)(κ2-H2BH·NR2H)H]BAr4F (R = Me, 5; R = H, 6), respectively. Heating 5 in the presence of Me3SiCH═CH2 led to alkene hydroboration and formation of the C–H activated product [Ru(IPr)(IPr)′(CO)]BAr4F (7). X-ray characterization of 3 and 5–7 was co...

Sensing of single nuclear spins in random thermal motion with proximate nitrogen-vacancy centers

Nitrogen-vacancy (NV) centers in diamond have emerged as valuable tools for sensing and polarizing spins. Motivated by potential applications in chemistry, biology, and medicine, we show that NV-based sensors are capable of detecting single spin targets even if they undergo diffusive motion in an ambient thermal environment. Focusing on experimentally relevant diffusion regimes, we derive an effective model for the NV-target interaction, where parameters entering the model are obtained from numerical simulations of the target motion. The practicality of our approach is demonstrated by analyzing two realistic experimental scenarios: (i) time-resolved sensing of a fluorine nuclear spin bound to an N-heterocyclic carbene-ruthenium (NHC-Ru) catalyst that is immobilized on the diamond surface and (ii) detection of an electron spin label by an NV center in a nanodiamond, both attached to a vibrating chemokine receptor in thermal motion. We find in particular that the detachment of a fluorine target from the NHC-Ru carrier molecule can be monitored with a time resolution of a few seconds.

Synthesis of ruthenium N-heterocyclic carbene complexes and their catalytic activity for β-alkylation of tertiary cyclic amines

The novel ruthenium N-Heterocyclic carbene complexes are synthesized, and characterized by studying its 1H, 13C, elemental analysis, and X-ray. These complexes have been reported as promising catalyst for β C–H bond functionalization of tertiary cyclic amines through hydrogen autotransfers in the presence of external acidic additive. The new catalytic products were characterized by 1H NMR, 13C NMR spectroscopic methods.

Erratum to: N-Propylphthalimide-Substituted Silver(I) N-Heterocyclic Carbene Complexes and Ruthenium(II) N-Heterocyclic Carbene Complexes: Synthesis and Transfer Hydrogenation of Ketones

This study deals with the synthesis of N-propylphthalimide substituted Ag(I)–N-heterocyclic carbene (NHC) complexes and N-propylphthalimide substituted Ru(II)–NHC complexes in the transfer hydrogenation of ketones. The Ag(I)–NHC complexes were synthesized from the imidazolium salts and Ag2O in dichloromethane at room temperature. The Ru(II)–NHC complexes have been prepared from Ag(I)–NHC complexes using transmetallation method. The six N-propylphthalimide substituted Ag(I)–NHC complexes and six N-propylphthalimide substituted Ru(II)–NHC complexes have been characterized by spectroscopic techniques and elemental analyses. N-propylphthalimide substituted Ru(II)–NHC complexes have been analyzed as catalysts for the transfer hydrogenation of ketones and exhibit activity in this reaction. This study deals with the synthesis of N-propylphthalimide substituted Ag(I)-N-heterocyclic carbene (NHC) complexes and N-propylphthalimide substituted Ru(II)–NHC complexes in the transfer hydrogenation of ketones. The Ag(I)–NHC complexes were synthesized from the imidazolium salts and Ag2O in dichloromethane at room temperature. The Ru(II)–NHC complexes have been prepared from Ag(I)–NHC complexes using transmetallation method. The six N-propylphthalimide substituted Ag(I)–NHC complexes and six N-propylphthalimide substituted Ru(II)–NHC complexeshavebeencharacterizedbyspectroscopictechniquesandelementalanalyses. N-propylphthalimide substituted Ru(II)–NHC complexes have been analyzed as catalysts for the transfer hydrogenation of ketones and exhibit activity in this reaction.

Latent ruthenium-indenylidene catalysts bearing a N-heterocyclic carbene and a bidentate picolinate ligand.

A silver-free methodology was developed for the synthesis of unprecedented N-heterocyclic carbene ruthenium indenylidene complexes bearing a bidentate picolinate ligand. The highly stable (SIPr)(picolinate)RuCl(indenylidene) complex 4a (SIPr = 1,3-bis(2-6-diisopropylphenyl)imidazolidin-2-ylidene) demonstrated excellent latent behaviour in ring closing metathesis (RCM) reaction and could be activated in the presence of a Brønsted acid. The versatility of the catalyst 4a was subsequently demonstrated in RCM, cross-metathesis (CM) and enyne metathesis reactions.

Net charge effects in N-heterocyclic carbene–ruthenium complexes with similar oxidation states and coordination geometries

A chelating benzimidazolylidene–carboxylate ligand (1) was transferred from [Ag(1)] to [RuCl2(dmso)4] to afford trans(C)-[Ru(1)2(bpy)] (2), but all attempts to incorporate 1 into cis(Cl)-[RuCl2(bpy)2] were unsuccessful. Alternatively, reaction of [RuCl(1)(η6-cymene)] (3) with bpy and AgOTf successfully produced [Ru(1)(bpy)2][OTf] (4). Methylation of 2 and 4 with MeOTf yielded trans(C)-[Ru(1-Me)2(bpy)][OTf]2 (5) and [Ru(1-Me)(bpy)2][OTf]2 (6), accompanied by a +2 and +1 increase in net charge, respectively. Cyclic voltammetry indicated that the increase in Ru(II)/Ru(III) oxidation potential from 2 to 5 was twice the increase from 4 to 6. UV–Vis spectroscopy also revealed that transitions in 5 occurred at higher energy than in 2 by double the difference between 6 and 4. Crystallographic analysis demonstrated that the coordination environment of Ru did not differ significantly between 2 and 5, suggesting that the observed shifts in oxidation potentials and absorption wavelengths are not due to changes in coordination chemistry or formal oxidation state. Collectively, these results show that 5 and 6 feature Ru centers more electron deficient than those in 2 and 4, respectively, by amounts linearly proportional to the difference in net charge.

Lipophilicity-dependent ruthenium N-heterocyclic carbene complexes as potential anticancer agents.

Five Ru(II)-N-heterocyclic carbenes (NHC) (1-5) were synthesized by reacting the appropriately substituted imidazolium chlorides with Ag2O, forming the NHC-silver chloride in situ followed by transmetalation with dimeric p-cymene ruthenium(II) dichloride. All the complexes were characterized by NMR and ESI-MS, and complex 1 was also characterized by single-crystal X-ray diffraction. The IC50 values of these five complexes were determined by the MTT-based assay on four human cancer cell lines, SKOV-3 (ovarian), PC-3 (prostate), MDA-MB-231 (breast) and EC109 (esophagus). The cytotoxicities of these complexes changed from a moderate effect to a fine one, corresponding to the increasing lipophilicity order of the complex of 2 < 1 < 3 < 4 < 5 (0.91, 0.88, 1.36, 1.85 and 2.62 for 1–5 respectively). Complex 5 showed the most cytotoxicity with the IC50 values 10.3 ± 0.3 μM for SKOV-3, 2.9 ± 0.1 μM for PC-3, 8.2 ± 0.6 μM for MDA-MB-231, 6.4 ± 0.2 μM for EC109 cell lines. Due to the superior cytotoxicity of complex 5 against the PC-3 cell lines, further biological evaluations were carried out to elucidate its action mechanism. The morphologic changes and cell cycle analysis showed that complex 5 can inhibit PC-3 cell lines by inducing cell cycle arrest at the G2/M phase. The DNA binding experiments further demonstrate that complex 5 has a better binding ability for DNA (Kb = 2.2 × 10(6) M(-1)) than complexes 1-4 (3.8 × 10(5), 7.0 × 10(5), 5.7 × 10(5), and 1.9 × 10(5) respectively).