Cyclometalated Ruthenium Complexes Research Articles

Organometallic Ru(III) Catalysts for α-Alkylation of Carbonyl Compounds using Alcohols: Mechanistic Insights via Detection of Key Intermediates.

Three novel cyclometalated ruthenium complexes ([Ru.L(9)] [Ru.L(10)] and [Ru.L(11)]) featuring azo functionalities were synthesized and characterized using a variety of spectroscopic techniques, namely FT-IR, electronic absorption spectroscopy, and ESI-MS. Representative solid-state structures of the acquired complexes were determined through X-ray crystallography. These complexes were evidenced to be efficient catalysts for the synthesis of various α-alkylated compounds utilizing simple acetophenone derivatives with easily affordable and economically viable alcohols, which were isolated and characterized via 1H and 13C NMR spectroscopy. The optimum reaction conditions were found by employing toluene as solvent, potassium tert-butoxide as base at 115 oC temperature utilizing 0.8 mol% of catalyst [Ru.L(10)]. The yield of the desired compounds found to be in the range of 83 - 97%. Additionally, mass spectrometry provided insights into the in-situ generated ruthenium hydride and ruthenium alkoxy intermediates, shedding light on the catalytic mechanism.

A colorimetric Ag+ chemosensor based on a cyclometalated ruthenium complex with deprotonated 2-phenylbenzimidazole

A cyclometalated ruthenium complex (1) using 2-phenylbenzimidazole as a C,N-ligand was developed as a colorimetric chemosensor to detect Ag+ ions. Upon the addition of Ag+ ions, the absorption spectra of complex 1 demonstrated no change in CH3CN solution. However, an excellent solution color change from dark-green to purple and absorption spectral change with a blue-shift of 27 nm (from 612 to 585 nm) were clearly observed after Ag+ ions were added to the solution of 1 with 2-fold of fluoride (denoted as 1 + F−). When Ag+ ions were replaced by other common metal ions, the solution color changed from green to red. Therefore, the solution of 1 + F− can be used to distinguish Ag+ from the other common metal ions. The absorption intensity at 612 nm exhibited a good linear correlation for the detection of Ag+ ion from 0 to 4 µM with a detection limit of 0.34 µM. According to the absorption and 1HNMR spectral changes of complex 1, the reaction mechanism is proposed to be as a coordination between silver ion and the deprotonated nitrogen in imidazole. However, the interactions of other metal ions with 1 + F− are related to a proton transfer process.

Cyclometalated ruthenium complexes overcome cisplatin resistance through PI3K/mTOR/Nrf2 signaling pathway.

Currently, cisplatin resistance remains a primary clinical obstacle in the successful treatment of non-small cell lung cancer. Here, we designed, synthesized, and characterized two novel cyclometalated Ru(II) complexes, [Ru(bpy)2(1-Ph-7-OCH3-IQ)] (PF6) (bpy=2,2'-bipyridine, IQ=isoquinoline, RuIQ7)and [Ru(bpy)2(1-Ph-6,7-(OCH3)2-IQ)] (PF6) (RuIQ8). As experimental controls, we prepared complex [Ru(bpy)2(1-Ph-IQ)](PF6) (RuIQ6) lacking a methoxy group in the main ligand. Significantly, complexes RuIQ6-8 displayed higher in vitro cytotoxicity when compared to ligands, precursor cis-[Ru(bpy)2Cl2], and clinical cisplatin. Mechanistic investigations revealed that RuIQ6-8 could inhibit cell proliferation by downregulating the phosphorylation levels of Akt and mTOR proteins, consequently affecting the rapid growth of human lung adenocarcinoma cisplatin-resistant cells A549/DDP. Moreover, the results from qRT-PCR demonstrated that these complexes could directly suppress the transcription of the NF-E2-related factor 2 gene, leading to the inhibition of downstream multidrug resistance-associated protein 1 expression and effectively overcoming cisplatin resistance. Furthermore, the relationship between the chemical structures of these three complexes and their anticancer activity, ability to induce cell apoptosis, and their efficacy in overcoming cisplatin resistance has been thoroughly examined and discussed. Notably, the toxicity test conducted on zebrafish embryos indicated that the three Ru-IQ complexes displayed favorable safety profiles. Consequently, the potential of these developed compounds as innovative therapeutic agents for the efficient and low-toxic treatment of NSCLC appears highly promising.

New cyclometalated Ru(ii) polypyridyl photosensitizers trigger oncosis in cancer cells by inducing damage to cellular membranes

A new generation of benzimidazole-based cyclometalated ruthenium(ii) complexes with bpy or dpq as ancillary ligands are effective against hypoxic cancers via green light activation and can directly disrupt phospholipid membranes and trigger oncosis.

Recent trends in the design and delivery strategies of ruthenium complexes for breast cancer therapy.

As the most frequent and deadly type of cancer in women, breast cancer has a high propensity to spread to the brain, bones, lymph nodes, and lungs. The discovery of cisplatin marked the beginning of the development of anticancer metal-based medications, although the drug's severe side effects have limited its usage in clinical settings. The remarkable antimetastatic and anticancer activity of different ruthenium complexes such as NAMI-A, KP1019, KP1339, etc. reported in the 1980s has bolstered the discovery of ruthenium complexes with various types of ligands for anticancer applications. The review meticulously elucidates the cytotoxic and antimetastatic potential of reported ruthenium complexes against breast cancer cells. Notably, arene-based and cyclometalated ruthenium complexes emerge as standout candidates, showcasing remarkable potency with notably low IC50 values. These findings underscore the promising therapeutic avenues offered by ruthenium-based compounds, particularly in addressing the challenges posed by conventional treatments in refractory or aggressive breast cancer subtypes. Moreover, the review comprehensively integrates a spectrum of ruthenium complexes, spanning traditional metal complexes to nano-based formulations and light-activated variants, underscoring the versatility and adaptability of ruthenium chemistry in breast cancer therapy.

Cyclometalated Half-Sandwich Ruthenium Complexes: Preparation, Structure, and Catalytic Synthesis of Phenolic Esters from Aryl Halides without Using External CO under Air.

A series of cyclometalated C,N-chelate half-sandwich ruthenium complexes based on N-heterocyclic ligands were prepared through a simple route with good yields. These air- and moisture-stable cyclometalated ruthenium complexes showed excellent catalytic efficiency in phenoxy carbonylation of aryl halides with phenyl formate derivatives as a CO source and phenol as a coupling partner under air. Ester products were obtained with high yields at room temperature and without the need for an inert atmosphere. The excellent catalytic activity, broad substrate range, and mild reaction conditions made this catalytic system potential for industrial production. In addition, DFT study has been carried out to elaborate the possible mechanism of this Ru-catalyzed reaction.

A colorimetric chemosensor for Cu2+/Hg2+ based on a cycloruthenated 2-phenylbenzimidazole

A cyclometalated ruthenium complex (1) with 2-phenylbenzimidazole as the ligand was synthesized and used as a colorimetric chemosensor to detect Hg2+ and Cu2+. It is interesting that the presence of Hg2+ caused a blue-shifted absorption of 1 from 560 to 450 nm resulting in a solution color change from red to yellow, while the addition of Cu2+ resulted in an attenuated absorption along with the solution color changing from red to colorless. Their corresponding detection limits were calculated to be 0.25 µM for Hg2+ and 0.45 µM for Cu2+, respectively. Moreover, the slips of paper were dyed with complex 1 and then successfully used to recognize Hg2+ and Cu2+ by naked eyes, respectively. Furthermore, 1 was also used to determine Hg2+ and Cu2+ in some spiked water samples, respectively.

Synthesis of Dibenzo[f,h]quinolines by Stepwise C–H Arylation of 2-Phenylpyridine and Reductive Cyclodehydrogenation

AbstractA synthetic approach to dibenzo[f,h]quinolines and their derivatives via stepwise ruthenium-catalyzed C–H arylation and potassium-mediated reductive cyclodehydrogenation from 2-phenylpyridine and aryl bromides, is presented. One dibenzo[f,h]quinoline derivative is used as a bidentate ligand to prepare a cyclometalated ruthenium complex. Two dibenzo[f,h]quinoline compounds and the ruthenium complex were characterized by single-crystal X-ray structural analysis.

High Intrinsic Phosphorescence Efficiency and Density Functional Theory Modeling of Ru(II)-Bipyridine Complexes with π-Aromatic-Rich Cyclometalated Ligands: Attributions of Spin-Orbit Coupling Perturbation and Efficient Configurational Mixing of Singlet Excited States.

A series of π-aromatic-rich cyclometalated ruthenium(II)-(2,2'-bipyridine) complexes ([Ru(bpy)2(πAr-CM)]+) in which πAr-CM is diphenylpyrazine or 1-phenylisoquinoline were prepared. The [Ru(bpy)2(πAr-CM)]+ complexes had remarkably high phosphorescence rate constants, k RAD(p), and the intrinsic phosphorescence efficiencies (ιem(p) = k RAD(p)/(νem(p))3) of these complexes were found to be twice the magnitudes of simply constructed cyclometalated ruthenium(II) complexes ([Ru(bpy)2(sc-CM)]+), where νem(p) is the phosphorescence frequency and sc-CM is 2-phenylpyridine, benzo[h]quinoline, or 2-phenylpyrimidine. Density functional theory (DFT) modeling of the [Ru(bpy)2(CM)]+ complexes indicated numerous singlet metal-to-ligand charge transfers for 1MLCT-(Ru-bpy) and 1MLCT-(Ru-CM), excited states in the low-energy absorption band and 1ππ*-(aromatic ligand) (1ππ*-LAr) excited states in the high-energy band. DFT modeling of these complexes also indicated phosphorescence-emitting state (Te) configurations with primary MLCT-(Ru-bpy) characteristics. The variation in ιem(p) for the spin-forbidden Te (3MLCT-(Ru-bpy)) excited state of the complex system that was examined in this study can be understood through the spin-orbit coupling (SOC)-mediated sum of intensity stealing (∑SOCM-IS) contribution from the primary intensity of the low-energy 1MLCT states and second-order intensity perturbation from the significant configuration between the low-energy 1MLCT and high-energy intense 1ππ*-LAr states. In addition, the observation of unusually high ιem(p) magnitudes for these [Ru(bpy)2(πAr-CM)]+ complexes can be attributed to the values for both intensity factors in the ∑SOCM-IS formalism being individually greater than those for [Ru(bpy)2(sc-CM)]+ ions.

Ru(II)-Catalyzed Hydroarylation of in situ Generated 3,3,3-Trifluoro-1-propyne by C-H Bond Activation: A Facile and Practical Access to β-Trifluoromethylstyrenes.

In this study, a practical and straightforward synthesis of β-(E)-trifluoromethylstyrenes by ruthenium-catalyzed C-H bond activation was developed. The readily available and inexpensive 2-bromo-3,3,3-trifluoropropene (BTP), a non-ozone depleting reagent, was used as a reservoir of 3,3,3-trifluoropropyne. With this approach, the monofunctionalization of a panel of heteroarenes was possible in a safe and scalable manner (23 examples, up to 87 % yield). Mechanistic investigations and density functional theory (DFT) calculations were also conducted to get a better understanding of the mechanism of this transformation. These studies suggested that 1) a cyclometallated ruthenium complex enabled the transformation, 2) this complex exhibited high efficiency in this transformation compared to the commercially available [RuCl2 (p-cymene)]2 and 3) the mechanism proceeded through a bis-cyclometallated ruthenium intermediate for the carboruthenation step.

Dissociation of Bipyridine and Coordination with Nitrosyl: Cyclometalated Ruthenium Nitrosyl Complex.

A novel family of ruthenium nitrosyl complexes [Ru(bpy)(C∧N)(MeCN)NO](PF6)2 (2a-2e, bpy = 2,2'-bipyridine, HC∧N = 2-phenylpyridine and its derivatives) has been prepared by reacting cyclometalated ruthenium complexes [Ru(bpy)2(C∧N)][PF6] (1a-1e) with NO+, which were comprehensively characterized by mass, IR, NMR, and UV-vis spectra as well as the single-crystal X-ray structure determinations. Herein, the coordination geometry of Ru atoms in 2a-2e is a distorted octahedron and {RuII-NO+}6 is present in these complexes. Theoretical calculations suggest that the reactions involving dissociation of one bipyridine and coordination with NO+ proceed spontaneously (ΔG < 0) and the transformation from 1a-1e to the intermediates is dominated by substituents (ΔGRI varies from -1.19 to -1.53 eV), which influence the binding energy between Ru(II) and NO+ in complexes 2a-2e (-89.42 to -101.17 kcal/mol) and thus control the photorelease of NO on a certain scale. The weak absorption bands in the visible region could be attributed to the contribution of dπ(RuII) → π*(NO+), which were enhanced greatly under light, indicating the possible release of NO. The photoinduced NO, as well as singlet oxygen (1O2), was then confirmed by EPR spectra, and the amount of NO released from 2a-2e was estimated via Griess reagent assay. The cytotoxicity of these complexes with or without visible light irradiation was also investigated using an MTT assay.

Cyclometallated Ruthenium Complex with 3,3',5,5'-Tetramethyl-1,1'-biphenyl-4,4'-bipyrazole and 2,2'-Dicarboxybipyridine: Synthesis, Optical Properties, and Quantum Chemical Modeling

New complex [RuL(Dmdcbp)2]PF6 (I) is synthesized by the consecutive reactions of [Ru-p-cymene]2Cl4 with 3,3',5,5'-tetramethyl-1,1'-biphenyl-4,4'-bipyrazole (L) and 4,4'-dicarboxy-2,2'-bipyridine in a methanol–chloroform medium. The composition of complex I is confirmed by NMR and elemental analysis, and the optical and luminescence properties of the complex are studied. Ligand L is characterized for the first time by X-ray diffraction (CIF file CCDC no. 2118676). Quantum chemical calculations in terms of the density functional theory are performed for the interpretation of the absorption and emission spectra. Complex I is promising for using as a photosensitizer.

Cycloruthenates(III) with CNO pincer-like ligands: Regioselective metallation of N-(4-R-benzoyl)-N′-(2-naphthylidene)hydrazines

Synthesis and characterization of a series of cyclometallated ruthenium(III) complexes with the Schiff bases N-(4-R-benzoyl)-N′-(2-naphthylidene)hydrazines (H2Ln, where n = 1–5 for R = H, Cl, Me, OMe and NO2, respectively) are described. All the complexes having the general molecular formula trans-[Ru(Ln)(PPh3)2Cl] (1–5) were characterized by elemental analysis, magnetic susceptibility, mass spectrometric, various spectroscopic (IR, UV-Vis and EPR) and electrochemical measurements. Molecular structures of trans-[Ru(L1)(PPh3)2Cl] (1) and trans-[Ru(L2)(PPh3)2Cl] (2) were confirmed by X-ray crystallography. In each of these two complexes, the metal center is in a distorted octahedral CNOClP2 coordination environment. The tridentate amidate-O, azomethine-N and the 2-naphthyl-C3 coordinating (L1/2)2– and the Cl– occupy the four equatorial positions and the P-atoms of the two triphenylphosphine molecules satisfy the two axial positions of the metal center. Electronic spectra of 1–5 in dichloromethane exhibit a ligand field transition within 1322–1160 nm and two ligand-to-metal and three intraligand transitions in the ranges 500–406 and 332–250 nm, respectively. The room temperature (300 K) magnetic moments of 1–5 are in the range of 1.86–1.99 µB. All five complexes display rhombic EPR spectra in frozen (77 K) dichloromethane-toluene (1:1) solution. A quasi-reversible reduction response in the range of –0.60–0.68 V and two irreversible oxidation responses around 0.9 and 1.4 V (vs. Ag/AgCl) were observed in the cyclic voltammograms of 1–5 in dichloromethane. Theoretical calculations were performed to get an insight of the regioselective ruthenation at the 3-position over the 1-position of the 2-naphthyl group of (Ln)2– in these complexes.

Recent Advances in Transition-Metal-Catalyzed Selective C–H Alkoxycarbonyldifluoromethylation Reactions of Aromatic Substrates

AbstractFluorine is well-known as a very special element. Approximately 30% of agrochemicals and 20% of all drugs contain fluorine; most of those compounds have unique functions in biochemistry, pharmacy, and bioscience and those containing alkoxycarbonyldifluoromethyl functional groups often have irreplaceable roles. Therefore, the selective introduction of alkoxycarbonyldifluoromethylated functional groups into various aromatic substrates has significant practical application. This review describes recent advances in selective alkoxycarbonyldifluoromethylation of aromatic substrates by using different catalytic strategies (cyclometalated ruthenium complex, transient regulating and visible-light-induced strategies).1 Introduction2 para-C–H Alkoxycarbonyldifluoromethylation of Aromatic Derivatives2.1 Ruthenium Catalysis2.2 Palladium Catalysis2.3 Visible-Light Catalysis2.4 Iron Catalysis3 meta-C–H Alkoxycarbonyldifluoromethylation of Aromatic Derivatives3.1 Ruthenium Catalysis3.2 Palladium Catalysis4 The Influence of Transition Metals and Directing Groups on Site Selectivity of Alkoxycarbonyldifluoromethylation4.1 The Influence of Directing Groups on the Site Selectivity of Alkoxycarbonyldifluoromethylation4.2 The Influence of Transition Metals on the Site Selectivity of Alkoxycarbonyldifluoromethylation5 Conclusions

Examination of N,N-dimethylbenzylamine as a substrate for ruthenium-catalysed C-H (thio)amidation: A mass spectrometry and DFT directed study

Key steps in the potential application of N,N-dimethylbenzylamine, a widely used substrate in organometallic chemistry, in ruthenium-catalysed C-H (thio)amidation have been examined. In particular, a cationic cyclometalated ruthenium(II) complex has been synthesised and characterised by X-ray crystallography and its insertion reactions with phenyl iso(thio)cyanate studied using electrospray ionisation high-resolution mass spectrometry (ESI-HRMS) and Density Functional Theory (DFT) calculations. The ruthenium(II) catalysed process proved to be inferior to synthesising (thio)amides by ortho-lithiation, iso(thio)cyanate insertion hydrolysis, and provide insights into mechanisms that are consistent with proposals reported in examination of 2-phenylpyridine as the substrate.

Ruthenium-Catalyzed Deuteration of Aromatic Carbonyl Compounds with a Catalytic Transient Directing Group.

Invited for the cover of this issue are Helfried Neumann, Matthias Beller and co-workers at the Leibniz-Institut für Katalyse e. V., Rostock and Hangzhou Normal University. The image depicts "the case of ketone deuteration" being solved by Sherlock Holmes. Read the full text of the article at 10.1002/chem.202100468.

Photoinduced ruthenium-catalyzed alkyl-alkyl cross-coupling reactions

C–H functionalization reactions constitute a key pillar in streamlining synthesis methods. In this context, the use of visible light to mediate metal-catalyzed C–H functionalization reactions is currently emerging as an important strategy to facilitate such transformations and enables mild C–H functionalization reactions at ambient conditions without the need for external photosensitizers or reactive reagents. Herein, we report on a photochemical approach that allows for C(sp3)–H functionalization reactions using simple [Ru(cymene)Cl2]2 and a phosphoric acid diester as catalysts. This strategy enables formal C(sp3)–C(sp3) coupling reactions to access valuable, sterically demanding amines and expands photochemical C–H functionalization reactions toward reaction pathways exclusive to photochemistry. Detailed mechanistic experiments and density functional theory calculations suggest the formation of a cyclometalated ruthenium complex that is stabilized by the phosphoric acid diester anion and serves as a catalyst for C–H functionalization reactions and single-electron transfer to access C–H functionalization reactions via a deprotonation-radical addition mechanism.

Multistate redox processes of structurally asymmetric diamines with a cyclometalated ruthenium bridge

Two structurally asymmetric cyclometalated ruthenium complexes 3(PF6) and 4(PF6), with an amine substituent on the cyclometalating and noncyclometalating ligand of each complex respectively, have been prepared and characterized. Three consecutive anodic redox couples are observed for these complexes in the potential window of 0 ~ +1.5 V vs Ag/AgCl, assigned to the stepwise oxidations of the ruthenium component and the two amine substituents. Upon stepwise oxidations with SbCl5, these complexes exhibit three-step absorption spectral changes in the near-infrared (NIR) region. At the singly-oxidized state, single-line or axial-like EPR signals are detected for 32+ and 42+, respectively. The NIR absorptions of 3n+ and 4n+ at different charge states (n = 2 – 4) are rationalized by time-dependent density functional theory calculations.

Photofunction‐Directed Coordination Molecular Engineering

AbstractMolecular engineering has emerged as a highly interdisciplinary field of study on function‐directed molecular design, material synthesis, and property optimization, accompanied by a deep understanding of the structure‐property relationship. In this review, our recent progress on the design and preparations of photofunctional metal complexes and related materials is summarized from the perspective of coordination molecular engineering. In particular, a series of cyclometalated diruthenium complexes with near‐infrared (NIR) electrochromic property have been synthesized by engineering the bridging ligand structures. A group of ruthenium‐amine conjugated complexes with multistage NIR electrochromism are obtained on the basis of a multicenter strategy. By engineering the ligand structures, a series of new ruthenium and platinum complexes are synthesized to show switchable luminescence in response to various stimuli. In addition, photoluminescent ruthenium, iridium, and platinum complexes are assembled to afford micro/nanocrystals with well‐defined morphology and luminescent properties. What is the most favorite and original chemistry developed in your research group?Ruthenium‐triarylamine conjugated system is one of my favorite topics.How do you get into this specific field?Molecular materials with multistage redox processes and multiple near‐ infrared absorptions are a challenging task in the field of electrochromism and molecular switching. The combination of cyclometalated ruthenium complexes and triarylamines allows us to solve this issue by using a multicenter strategy with a great structural and functional diversity.What is the most important personality for scientific research?Personally, I consider honesty, curiosity, and persistence are the most important and fundamental personalities in carrying out scientific research.What's your hobbies?I enjoy playing basketball and watching basketball matches in leisuretime.How do you keep balance between research and family?I like managing time by prioritizing daily tasks. If time permits, I'm glad to join family activities in cooking, walking, exercising, etc. I always appreciate and support my wife's career and my daughter's studies, from which I receive their returns in support of my career.Could you please give us some advices on improving Chinese Journal of Chemistry?Chin. J. Chem. is a classical and influential journal of chemistry. The impact of the journal keeps increasing especially in recent years. In my point of view, it would be helpful for the journal by keeping a balance among different subjects of chemistry while welcoming manuscripts on material and energy‐related interdisciplinary researches. In addition, in order to further boost its global reputation, I would like to suggest inviting more international scientists to contribute to the journal.

Efficient methylation of anilines with methanol catalysed by cyclometalated ruthenium complexes

Cyclometalated ruthenium allow the effective and selective N-methylation of anilines under mild conditions.