Rhodium Complexes Research Articles

In vitro and in vivo anticancer activity of novel Rh(III) and Pd(II) complexes with pyrazolopyrimidine derivatives

Six pyrazolopyrimidine rhodium(III) or palladium(II) complexes, [Rh(L1)(H2O)Cl3] (1), [Rh(L2)(CH3OH)Cl3] (2), [Rh(L3)(H2O)Cl3] (3), [Rh2(L4)Cl6]·CH3OH (4), [Rh(L5)(CH3CN)Cl3]·0.5CH3CN (5), and [Pd(L5)Cl2] (6), were synthesized and characterized. These complexes showed high cytotoxicity against six tested cancer cell lines. Most of the complexes showed higher cytotoxicity to T-24 cells in vitro than cisplatin. Mechanism studies indicated that complexes 5 and 6 induced G2/M phase cell cycle arrest through DNA damage, and induced apoptosis via endoplasmic reticulum stress response. In addition, complex 5 also induced cell apoptosis via mitochondrial dysfunction. Complexes 5 and 6 showed low in vivo toxicity and high tumor growth inhibitory activity in mouse tumor models. The inhibitory effect of rhodium complex 5 on tumor growth in vivo was more pronounced than that of palladium complex 6.

Structural Effect of Water-Soluble Zinc Porphyrins in a Visible-Light Driven NADH Regeneration System Catalyzed by Rhodium Pentamethylcyclopentadienyl Complex

Abstract The effect of ionic substituents (4-sulfonatophenyl, 4-carboxyphenyl, 4-methylpyridyl, and 4-N,N,N-trimethylaminophenyl-groups) of water-soluble zinc porphyrin (ZnP) on the visible light-driven NADH regeneration by a system of triethanolamine, ZnP, and rhodium complex [Cp*Rh(bpy)(H2O)]2+ (Cp* = pentamethylcyclopentadienyl, bpy = 2,2′-bipyridyl) was studied to provide significant guidance for hybridization with a wide range of oxidoreductases.

Half-Sandwich Iridium(III), Rhodium(III), and Ruthenium(II) Complexes Chelating Hybrid sp2-N/sp3-N Donor Ligands to Achieve Improved Anticancer Selectivity.

The biological efficacy of half-sandwich platinum group organometallic complexes of the formula [(η5-Cpx)/(η6-arene)M(XY)Cl]0/+ (XY = bidentate ligands; Cpx = functionalized cyclopentadienyl; M = Ir, Rh, Ru, Os) has received considerable attention due to the significance of the metal center, chelating ligand, and Cpx/arene moieties in defining their anticancer potency and selectivity. With a facile access to the BIAN-derived imine-amine ligands using alkylaluminum as the reductant, we herein described the preparation and characterization of 16 half-sandwich Ir(III), Rh(III), and Ru(II) complexes chelating the hybrid sp2-N/sp3-N donor ligand. A nonplanar five-member metallacycle was confirmed by X-ray single-crystal structures of Ir1-Ir3, Ir7, Rh1, Ru1, and Ru4. The attempt to prepare imine-amido complexes using a base as the deprotonating agent led to the mixture of imine-amine complexes, within which the leaving group Cl- was displaced, and 16-electron imine-amido complexes without Cl-. The half-sandwich imine-amine complexes in this system underwent rapid hydrolysis in aqueous solution, exhibited weak photoluminescence, and showed the ability of binding to CT-DNA and BSA. The cytotoxicity of all imine-amine complexes against A549 lung cancer cell lines, HeLa cervical cancer cell lines, and 4T1 mouse breast cancer cells was determined by an MTT assay. The IC50 values of these complexes were in a range of 5.71-67.28 μM. Notably, most of these complexes displayed improved selectivity toward A549 cancer cells versus noncancerous BEAS-2B cells in comparison with the corresponding α-diimine complexes chelating the sp2-N/sp2-N donor ligand, which have been shown no selectivity in our previous report. The anticancer selectivity of these complexes appeared to be related to the redox-based mechanism including the catalytic oxidation of NADH to NAD+, reactive oxygen species (ROS) generation, and depolarization of the mitochondrial membrane. Further, inducing apoptosis of these complexes in A549 cancer cells and BEAS-2B normal cells also correlated with their anticancer selectivity, indicating the apoptosis mode of cell death in this system. In addition, these complexes could enter A549 cells via energy-dependent pathway and were able to impede the in vitro migration of A549 cells.

Syntheses, Crystal and Electronic Structures of Rhodium and Iridium Pyridine Di-Imine Complexes with O- and S-Donor Ligands: (Hydroxido, Methoxido and Thiolato)

The syntheses of new neutral square-planar pyridine di-imine rhodium and iridium complexes with O- and S-donor (OH, OR, SH, SMe and SPh) ligands along with analogous cationic compounds are reported. Their crystal and electronic structures are investigated in detail with a focus on the non-innocence/innocence of the PDI ligand. The oxidation states of the metal centers were analyzed by a variety of experimental (XPS and XAS) and theoretical (LOBA, EOS and OSLO) methods. The dπ-pπ interaction between the metal centers and the π-donor ligands was investigated by theoretical methods and revealed the partial multiple-bond character of the M-O,S bonds. Experimental support is provided by a sizable barrier for the rotation about the Ir-S bond in the methyl thiolato complex and confirmed by DFT and LNO-CCSD(T) calculations. This was corroborated by the high Ir-O and Ir-S bond dissociation enthalpies calculated at the PNO-CCSD(T) level.

Plus‐Size DiPAMP Hybrids for Advanced Rhodium(I)‐Catalyzed Hydrogenation: The 2RBigFUS Model

AbstractOutfitting the P,P′‐distereogenic 2MeBigFUS ligand with the characteristic branched/functionalized‐alkoxy feature of the R‐SMS‐Phos design furnished the 2RBigFUS family (Figure 2). Rhodium(I) complexes thereof exhibited a further boosted activity and superior enantioselectivity in the hydrogenation of various functionalized olefins, including the challenging α‐arylacrylic acids. The application under practical conditions to enantiomeric active pharmaceutical ingredients (APIs) and relevant synthetic building blocks capped the outcome.

Observation of a light-induced short-lived excimer in a crystal of a fluorescent rhodium complex via time-resolved Laue photocrystallography

Observation of a light-induced short-lived excimer in a crystal of a fluorescent rhodium complex <i>via</i> time-resolved Laue photocrystallography

Open-Cage Fullerene as a Macrocyclic Ligand for Na, Pt, and Rh Metal Complexes.

An open-cage [60]fullerene derivative was prepared through Malaprade oxidation of a vicinal triol moiety as the key step. Above the 17-membered orifice, there is one carboxyl group. Three ketone carbonyl groups and one lactone carbonyl group are located on the rim of the orifice. The carboxylic and carbonyl oxygen atoms around the orifice act as strong polydentate ligands for a sodium ion. These oxygen atoms also react with [Rh(CO)2Cl]2 to form various isomeric rhodium complexes with comparable stability. The fullerene C═C bond on the rim of the orifice forms a stable platinum complex when treated with Pt(PPh3)4. Single crystal X-ray diffraction data reveal that one of the carboxylic oxygen atoms above the orifice forms a H-bond with the water molecule trapped in the cage.

Variable coordination behavior of rhodium metal complexes towards thiourea derivative ligands in comparison to its ruthenium and iridium analogs: Synthesis and biological studies

Reactions of arene d6 platinum group metal dimers [(arene)MCl2]2 (where M =Ru/Rh/Ir and arene = p-cymene, Cp*) with thiourea derivatives L1 {2-(3-methoxybenzoyl)-N-phenylhydrazinecarbothioamide}, L2 {2-benzoyl-N-phenylhydrazinecarbothioamide} and L3 {N-phenyl-2-(thiophene-2-carbonyl)hydrazinecarbothioamide} yielded a series of mononuclear neutral complexes (1–9) formulated as [(arene)M(L)к2(N∩S)Cl] {where L = L1, L2, L3, M =Ru, Ir, arene = p-cymene, Cp*} and [Cp*Rh(L)к1(S)Cl2] {where L = L1, L2, L3}. Further, treatment of monodentate rhodium complexes with sodium azide resulted in interesting dinuclear sulfur bridged complexes (10–12). These complexes have been characterized by various spectroscopic techniques such as FT-IR, UV–Vis, NMR spectroscopy and ESI-Mass spectrometry. The solid-state structures of the representative complexes determined by single-crystal X-ray diffraction studies showed that the ligands exhibit versatile coordination modes. In vitro antibacterial activity was evaluated against human pathogenic bacteria by the agar well diffusion method, which revealed their significant activity against both Gram-positive (Staphylococcus aureus and Bacillus thuringiensis) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria. Furthermore, antioxidant activity by DPPH assay revealed that the ligands and complexes are potent antioxidants.

Heterobimetallic Trihydrido Complex of Ruthenium and Rhodium Supported by Cyclopentadienyl Groups with Different Steric Demands

Heterobimetallic Trihydrido Complex of Ruthenium and Rhodium Supported by Cyclopentadienyl Groups with Different Steric Demands

Rhodium(III)-Picolinamide Complexes Act as Anticancer and Antimetastasis Agents via Inducing Apoptosis and Autophagy.

As a continuation of our endeavors in discovering metal-based drugs with cytotoxic and antimetastatic activities, herein, we reported the syntheses of 11 new rhodium(III)-picolinamide complexes and the exploration of their potential anticancer activities. These Rh(III) complexes showed high antiproliferative activity against the tested cancer cell lines in vitro. The mechanism study indicated that Rh1 ([Rh(3a)(CH3CN)Cl2]) and Rh2 ([Rh(3b)(CH3CN)Cl2]) inhibited cell proliferation by multiple modes of action via cell cycle arrest, apoptosis, and autophagy and inhibited cell metastasis via FAK-regulated integrin β1-mediated suppression of EGFR expression. Furthermore, Rh1 and Rh2 significantly inhibited bladder cancer growth and breast cancer metastasis in a xenograft model. These rhodium(III) complexes could be developed as potential anticancer agents with antitumor growth and antimetastasis activity.

Cytotoxic Activities of Half‐sandwich M(III) Complexes (M=Rh, Ir) Bearing Chloro‐substituted Bidentate‐coordinated Phenanthroline or Terpyridine Ligands

AbstractThe synthesis and characterization of four compounds [M(η5‐C5Me5)(N^N)Cl]PF6 [N^N=4,7‐dichloro‐1,10‐phenanthroline with M=Rh, 1, and M=Ir, 2, and N^N=4'‐(4‐chlorophenyl)‐2,2':6',2''‐terpyridine in the κ2N,N'‐coordination mode with M=Rh, 3, and M=Ir, 4] are described. All compounds were characterized by spectroscopic means and their molecular structures in the crystal were confirmed by single‐crystal X‐ray diffraction studies. The cytotoxicity of all compounds was evaluated by MTT assay against the three cancer cell lines HeLa (cervical carcinoma), HT‐29 (colon adenocarcinoma) and MCF‐7 (human breast adenocarcinoma). The complexes 3 and 4 display promising activity with IC50 values of 1 μM. The rhodium(III) complex 1 also shows highly improved cytotoxicity compared to cisplatin against the cancer cell lines HT‐29 and MCF‐7. In contrast to this, the iridium(III) complex 2 is even less active against the HeLa cell line than cisplatin.

Moving from Fuel to Feedstock

Carbon-hydrogen bond activations and their subsequent functionalisation have long been an important target in chemistry because C–H bonds are ubiquitous throughout nature, making C–H derivatisation reactions highly desirable. The selective and efficient functionalisation of this bond into many more useful carbon-element bonds (for example, C–B, C–Si, C–O and C–S bonds) would have many uses in pharmaceutical and bulk chemical synthesis. Activation of the C–H bond is, however, challenging due to the high strength and low bond-polarity of this bond rendering its cleavage unfavourable. With the correct choice of reagents and systems, especially those utilising directing groups, kinetically and thermodynamically favourable catalytic processes have been developed. However, a key remaining challenge is the development of undirected, intermolecular reactions using catalysts that are both selective and active enough to make useful processes. In this review, the progress towards optimising Group 9 C–H activation catalysts is discussed, particularly focusing on undirected reactions that are kinetically more difficult, starting with a brief history of C–H activation, identifying the importance of auxiliary ligands including the nature of anionic ligand (for example, cyclopentadienyl, indenyl, fluorenyl and trispyrazolylborate) and neutral ligands (such as phosphines, carbonyl, alkenes and N-heterocyclic carbenes (NHCs)) that contribute towards the stability and reactivity of these metal complexes. The tethering of the anionic ligand to strong σ-donating ligands is also briefly discussed. The focus of this review is primarily on the Group 9 metals rhodium and iridium, however, C–H activation using Group 8 and 10 metals are compared where useful. The most recent advances in this field include the development of C–H borylation of many small hydrocarbon substrates such as arenes, heterocycles and n-alkanes as well as the more challenging substrate methane.

3-acetyl-coumarin-substituted thiosemicarbazones and their ruthenium, rhodium and iridium metal complexes: An investigation of the antibacterial, antioxidant and cytotoxicity activities

A series of ruthenium, iridium and rhodium half-sandwich complexes containing 3-acetyl chromen-2-one-4(N)-substituted thiosemicarbazone derivatives have been prepared for use as antibacterial and anticancer agents. These complexes have been isolated as cationic bidentate (N, S) and neutral bidentate (N, S) complexes. The complexes have been characterized by spectral techniques (FT-IR, UV-Vis, NMR and HRMS) and single-crystal X-ray crystallography methods. The structure of complex 6 has been determined by a single-crystal X-ray diffraction study, which shows that coordination of the 3-acetyl chromen-2-one-4(N)-substituted thiosemicarbazone ligand to the metal occurs via azomethine nitrogen and thiolate sulfur atoms. Vitro antibacterial activity against gram-positive Staphylococcus aureus and gram-negative Escherichia coli, Klebsiella pneumonia strains and antioxidant activity have been evaluated. Also, the said complexes were tested for anticancer efficacy (in vitro for 48h) in Dalton's lymphoma (DL) cancer cell lines using cell cytotoxicity (MTT) and apoptosis tests. The results were compared with cisplatin (standard drug) under identical experimental conditions. The cell cytotoxicity results showed that complex 5 induced higher cytotoxicity in DL cells, followed by complex 4, 1, and 2.

Selective Hydrogenation of Lignin-derived Aromatics to Give Cyclohexanes with a Rhodium-Pincer Precatalyst

Catalytic hydrogenation of aromatic rings represents an essential industrial chemical process for the synthesis of commodity chemicals and intermediates in pharmaceuticals, polymers, and fine chemicals. Herein, we report an air-stable rhodium complex bearing a pincer bis(oxazolinyl)phenyl ligand that shows good catalytic activity for the hydrogenation of lignin-derived acetophenones, benzoic acids as well as other functionalised aromatics to the corresponding alicyclic products by reducing the aryl groups. The rhodium complex is a precatalyst, offering easy access to active rhodium species, which appears to be heterogeneous in the hydrogenation.

Ruthenium, rhodium and iridium complexes of a silyl-substituted N-heterocyclic carbene ligand and their catalytic performance in hydrosilylation of terminal alkynes

Herein, [Ru(NHC)(p-cymene)Cl2] (3) and [MCl(NHC)(cod)] (M=Rh (4) or Ir (5)) (cod=1,5‒cyclooctadiene) complexes of a silyl‒substituted N-heterocyclic carbene ligand (NHC) have been prepared by the transmetalation reaction between Ag‒NHC (2) and corresponding starting metal compound. The characterization of the complexes has been completed by NMR spectroscopy and elemental analyses. Solid state structures of Ag- (2) and Rh-NHC (4) have also been determined by single crystal X-ray analysis. [RhCl(NHC)(CO)2] type bis-carbonyl complex (6) has also been prepared and CO stretching frequencies pointed the strong σ‒donor ability of the silyl-substituted NHC. The catalytic activity of all complexes have been examined in hydrosilylation of terminal alkynes. Among the complexes, Ir-NHC has been found out as active catalyst with around 90% conversion and β‒(Z) selectivity at room temperature. Further studies revealed that this complex is able to maintain its stability in catalytic reaction conditions, chemoselective to alkynes in the presence of alkenes, and operable in scale-up reactions. In contrast, bis-carbonyl Rh-NHC performed 82% β‒(Z) selectivity with full conversion of alkyne in first 4 h of reaction, but when reaction time was extended to 24 h, almost all β‒(Z) vinylsilane isomerised to thermodynamically more stable β‒(E).

Synthesis of Hexamethyl-1,1′-spirobiindane-Based Chiral Spiro Cp Ligands and Their Application in Rhodium-Catalyzed Enantioselective Aryl C–H Addition to Nitroalkenes

Spiro cyclopentadienyl rhodium (SCpRh) complexes are powerful catalysts for promoting asymmetric C–H functionalization reactions. However, the application of chiral SCp ligands is limited due to tedious synthetic procedures and expensive starting materials. Herein, we have developed a series of chiral spiro ligands (BCSCp) with 6–7 steps from commercially available and cheap Bisphenol C. Their corresponding rhodium complexes have been prepared and successfully applied in enantioselective aryl C–H addition to nitroalkenes, affording a series of C–H adducts in up to 88% yield with up to 98% ee.

Factors determining rhodium solubilization efficiency in molten K2CO3–K2O–B2O3–Al2O3 medium

Dilute-acid-soluble, complex rhodium oxides were generated in a molten K2CO3–K2O–B2O3–Al2O3 medium, and factors affecting their generation efficiency were investigated. Surface observation revealed that planar-shaped materials (the insoluble rhodium compounds) were covered by fine particles (the acid-soluble rhodium compounds) in the heat-treated rhodium. The fine particles contained Rh, K, Al, B, Ca, Si, and O. In contrast, the main components of the insoluble rhodium compounds were Rh, K, Al, Si, and O. Therefore, an efficient reaction of B and Ca with rhodium is an essential factor in solubilizing rhodium. The oxidation state of rhodium in the acid-soluble compounds was higher than that of the insoluble rhodium compounds, implying that efficient rhodium oxidation is another factor for rhodium solubilization. When air was supplied while synthesizing the rhodium compounds to enhance the oxidizing condition, rhodium extraction from the obtained heat-treated products increased to 74%.

Cytotoxic potential of silver, palladium, rhodium, ruthenium, and iridium complexes of a cycloheptyl-substituted lipophilic N-heterocyclic carbene ligand

Lipophilicity is a crucial parameter for cytotoxicity of metal complexes, in many cases associated with increased activity. In the present study, we synthesized a series of N-heterocyclic carbene (NHC) complexes of different metals with a lipophilic benzimidazolium chloride to investigate and compare their cytotoxicity. Rh– (4), Ru– (5), and Ir–NHC (6) complexes of a cycloheptyl-substituted benzimidazole-based NHC ligand (1) have been prepared by transmetalation reaction between Ag–NHC and the corresponding metal compound. The newly synthesized complexes have been characterized by NMR, IR, LC-MS spectroscopy, and elemental analyses. The anti-growth effects of the newly synthesized Rh–, Ru–, and Ir–NHC complexes and previously reported NHC precursor (1), Ag– (2), and Pd–NHC (3) complexes against human breast (MCF-7), colorectal (Caco-2), ovarian (A2780), and prostate (LNCaP) cancer cell lines have been investigated by MTT assay. The results revealed that the compounds provide stronger anti-growth effects against all cell lines compared to standard drug cisplatin. Among the compounds, benzimidazolium chloride, and Ag–NHC complex showed promising activities.

Ruthenium, rhodium, and iridium complexes featuring fluorenyl benzohydrazone derivatives: Synthesis and preliminary investigation of their anticancer and antibacterial activity

A convenient synthesis of twelve complexes (1–12) of ruthenium(II), rhodium(III) and iridium(III) containing fluorenyl benzohydrazone ligands having the general formula [(arene)M(L)Cl] (arene: benzene/p-cymene/Cp*; l-bidentate substituted benzoyl hydrazone derivatives) has been carried out. The characterization of the complexes has been done by FT-IR, UV–Vis, NMR and X-ray crystallographic studies. The metal complexes exhibit N∩O binding mode through the azomethine nitrogen and the imidolate oxygen forming a five-membered chelating ring. All the compounds were tested for their antibacterial properties against three strains of bacterial microorganisms - Staphylococcus aureus (+ve), Klebsiella pneumoniae (-ve) and Escherichia coli (-ve). In-vitro assay results further revealed that complexes 4 and 6 significantly act against Gram-positive (Staphylococcus aureus) and Gram-negative (E. coli and Klebsiella pneumoniae). An in-vitro assessment of the cytotoxic effects of both the complexes and ligands was performed, and the findings indicate that complex 9 exhibited the most promising results with the lowest IC50 value in terms of cell viability percentage against HeLa cell lines. These results highlight the potential of further investigating the anticancer properties of this particular complex.

Hexaazatrinaphthalene-Based Covalent Triazine Framework-Supported Rhodium(III) Complex: A Recyclable Heterogeneous Catalyst for the Reductive Amination of Ketones to Primary Amines.

The development of efficient and recyclable heterogeneous catalysts is an important topic. Herein, a rhodium(III) complex Cp*Rh@HATN-CTF was synthesized by the coordinative immobilization of [Cp*RhCl2]2 on a hexaazatrinaphthalene-based covalent triazine framework. In the presence of Cp*Rh@HATN-CTF (1 mo l% Rh), a series of primary amines could be obtained via the reductive amination of ketones in high yields. Moreover, catalytic activity of Cp*Rh@HATN-CTF is well maintained during six runs. The present catalytic system was also applied for the large scale preparation of a biologically active compound. It would facilitate the development of CTF-supported transition metal catalysts for sustainable chemistry.