Cytotoxicity of Ruthenium(II) Arene Complexes Containing Functionalized Ferrocenyl β-Diketonate Ligands.

The synthesis and characterization of 24 ruthenium(II) arene complexes of the type [(-cym)RuCl(Fc-acac)] (where -cym = p-cymene and Fc-acac = functionalized ferrocenyl β-diketonate ligands) are reported, including single-crystal X-ray diffraction for 21 new complexes. Chemosensitivity studies have been conducted against human pancreatic carcinoma (MIA PaCa-2), human colorectal adenocarcinoma -wildtype (HCT116 ) and normal human retinal epithelial cell lines (APRE-19). The most active complex, which contains a 2-furan-substituted ligand (), is 5x more cytotoxic than the analogs 3-furan complex () against MIA PaCa-2.

Correction: Heteroleptic iron(II) complexes of chiral 2,6-bis(oxazolin-2-yl)-pyridine (PyBox) and 2,6-bis(thiazolin-2-yl)pyridine ligands - the interplay of two different ligands on the metal ion spin state.

Correction for 'Heteroleptic iron(II) complexes of chiral 2,6-bis(oxazolin-2-yl)-pyridine (PyBox) and 2,6-bis(thiazolin-2-yl)pyridine ligands - the interplay of two different ligands on the metal ion spin state' by Namrah Shahid , , 2022, , 4262-4274, DOI: 10.1039/d2dt00393g.

Heteroleptic iron(II) complexes of chiral 2,6-bis(oxazolin-2-yl)-pyridine (PyBox) and 2,6-bis(thiazolin-2-yl)pyridine ligands - the interplay of two different ligands on the metal ion spin sate.

Complexation of Fe[ClO]·6HO by 1 equiv. 2,6-bis((4)-4-phenyl-4,5-dihydrooxazol-2-yl)pyridine (()-LPh) and 2,6-bis((4)-4-phenyl-4,5-dihydrothiazol-2-yl)pyridine (()-LPh) cleanly affords [Fe(()-LPh)(()-LPh)][ClO]; [Fe(()-LiPr)(()-LiPr)][ClO] (LiPr = 2,6-bis(4-isopropyl-4,5-dihydrooxazol-2-yl)pyridine; LiPr = 2,6-bis(4-isopropyl-4,5-dihydrothiazol-2-yl)pyridine) was prepared by a similar route. The compounds exhibit thermal spin-crossover in solution, at temperatures midway between the corresponding [Fe(()-LR)(()-LR)][ClO] and [Fe(()-LR)(()-LR)][ClO] (R = Ph or iPr) species.

Spin-States of Diastereomeric Iron(II) Complexes of 2,6-Bis(thiazolin-2-yl)pyridine (ThioPyBox) Ligands and a Comparison with the Corresponding PyBox Derivatives.

This report investigates homoleptic iron(II) complexes of thiazolinyl analogues of chiral PyBox tridentate ligands: 2,6-(4-phenyl-4,5-dihydrothiazol-2-yl)pyridine (Ph), 2,6-(4-propyl-4,5-dihydrothiazol-2-yl)pyridine (Pr), and 2,6-(4--butyl-4,5-dihydrothiazol-2-yl)pyridine (-Bu). Crystallographic data imply the larger and more flexible thiazolinyl rings reduce steric clashes between the R substituents in homochiral [Fe(()-R)] or [Fe(()-R)] (R = Ph, Pr, or -Bu), compared to their PyBox (R) analogues. Conversely, the larger heterocyclic S atoms are in close contact with the R substituents in heterochiral [Fe(()-Ph)(()-Ph)], giving it a more sterically hindered ligand environment than that in [Fe(()-Ph)(()-Ph)] (Ph = 2,6-(4-phenyl-4,5-dihydrooxazol-2-yl)pyridine).

Bis(N-picolinamido)cobalt(II) Complexes Display Antifungal Activity toward Candida albicans and Aspergillus fumigatus.

This report highlights the synthesis and characterization of ten new bis(N-picolinamido)cobalt(II) complexes of the type [(L) CoX ] , whereby L=N-picolinamide ligand and X=diisothiocyanato (-NCS), dichlorido (-Cl) or diaqua (-OH ) ligands. Single crystal X-ray (SC-XRD) analysis for nine of the structures are reported and confirm the picolinamide ligand is bound to the Co(II) center through a neutral N,O binding mode. With the addition of powder X-ray diffraction (PXRD), we have confirmed the cis and trans ligand arrangements of each complex.

Rhodium(III) Dihalido Complexes: The Effect of Ligand Substitution and Halido Coordination on Increasing Cancer Cell Potency.

This work presents the synthesis of eight new rhodium(III) dihalido complexes, [RhX(L)(LH)] (where X = Cl or I), which incorporate two bidentate -(3-halidophenyl)picolinamide ligands. The ligands have different binding modes in the complexes, whereby one is neutral and bound (LH) coordination, while the other is anionic and bound (L) coordination. The solid state and solution studies confirm multiple isomers are present when X = Cl; however, after a halide exchange with potassium iodide (X = I) the complexes exist exclusively as single stable isomers.

Bis(bipyridine)ruthenium(II) Ferrocenyl β-Diketonate Complexes: Exhibiting Nanomolar Potency against Human Cancer Cell Lines.

The synthesis and characterization of new bis(bipyridine)ruthenium(II) ferrocenyl β-diketonate complexes, [(bpy) Ru(Fc-acac)][PF ] (bpy=2,2'-bipyridine; Fc-acac=functionalized ferrocenyl β-diketonate ligand) are reported. Alongside clinical platinum drugs, these bimetallic ruthenium-iron complexes have been screened for their cytotoxicity against MIA PaCa-2 (human pancreatic carcinoma), HCT116 p53 (human colon carcinoma, p53-wild type) and ARPE-19 (human retinal pigment epithelial) cell lines. With the exception of one complex, the library exhibit nanomolar potency against cancerous cell lines, and their relative potencies are up to 40x, 400x and 72x more cytotoxic than cisplatin, carboplatin and oxaliplatin, respectively.

The facile and additive-free synthesis of a cell-friendly iron(iii)-glutathione complex.

The straightfoward creation of an unreported glutathione-stabilised iron(iii) complex is disclosed. In contrast to previous reports, glutathione was shown to coordinate and stabilise iron directly under physiological conditions in the absence of additional sulfur containing molecules, such as sodium sulfide. The complex was extensively characterised; the molecular geometry was determined as two inequivalent octahedra, approximately 2/3 of which are slightly distorted towards more tetrahedral in character, with the remaining 1/3 more regularly octahedral.

β-Diketonate versus β-Ketoiminate: The Importance of a Ferrocenyl Moiety in Improving the Anticancer Potency.

Herein we present a library of fully characterized β-diketonate and β-ketoiminate compounds that are functionalized with a ferrocenyl moiety. Their cytotoxic potential has been determined by screening against human breast adenocarcinomas (MCF-7 and MDA-MB-231), human colorectal carcinoma p53 wild type (HCT116 p53 ) and normal human prostate (PNT2) cell lines. The ferrocenyl β-diketonate compounds are more than 18 times more cytotoxic than the ferrocenyl β-ketoiminate analogues.

β-Ketoiminato Iridium(III) Organometallic Complexes: Selective Cytotoxicity towards Colorectal Cancer Cells HCT116 p53-/.

This report presents a new library of organometallic iridium(III) compounds of the type [Cp*IrCl(L)] (Cp*=pentamethylcyclopentadienyl and L=a functionalized β-ketoiminato ligand) showing moderate to high cytotoxicity against a range of cancer cell lines. All compounds show increased activity towards colorectal cancer, with preferential activity observed against the immortalized p53-null colorectal cell line, HCT116 p53-/-, with sensitivity factors (SF) up to 26.7.

Bis-picolinamide Ruthenium(III) Dihalide Complexes: Dichloride-to-Diiodide Exchange Generates Single trans Isomers with High Potency and Cancer Cell Selectivity.

A library of new bis-picolinamide ruthenium(III) dihalide complexes of the type [RuX L ] (X=Cl or I, L=picolinamide) have been synthesised and characterised. The complexes exhibit different picolinamide ligand binding modes, whereby one ligand is bound (N,N) and the other bound (N,O). Structural studies revealed a mixture of cis and trans isomers for the [RuCl L ] complexes but upon a halide exchange reaction to yield [RuI L ], only single trans isomers were detected.

Cytotoxic hydrogen bridged ruthenium quinaldamide complexes showing induced cancer cell death by apoptosis.

This report presents the first known p-cymene ruthenium quinaldamide complexes which are stabilised by a hydrogen-bridging atom, [{(p-cym)Ru(II)X(N,N)}{H(+)}{(N,N)XRu(II)(p-cym)}][PF6] (N,N = functionalised quinaldamide and X = Cl or Br). These complexes are formed by a reaction of [p-cymRu(μ-X)2]2 with a functionalised quinaldamide ligand. When filtered over NH4PF6, and under aerobic conditions the equilibrium of NH4PF6 ⇔ NH3 + HPF6 enables incorporation of HPF6 and the stabilisation of two monomeric ruthenium complexes by a bridging H(+), which are counter-balanced by a PF6 counterion.

Increasing anti-cancer activity with longer tether lengths of group 9 Cp* complexes.

Here in, we report the cytotoxicity of both rhodium and iridium functionalised Cp* analogues of the [Cp*MCl2]2 dimers. The functionalised dimers contain a hydroxy tethered arm of differing carbon length. These show promising IC50 values when tested against HT-29, A2780 and cisplatin-resistant A2780cis human cancer cell lines, with the cytotoxicity improving proportionally with an increase in carbon tether length of the Cp* ring.

Hypoxia-Sensitive Metal β-Ketoiminato Complexes Showing Induced Single-Strand DNA Breaks and Cancer Cell Death by Apoptosis.

A series of ruthenium and iridium complexes have been synthesized and characterized with 20 novel crystal structures discussed. The library of β-ketoiminato complexes has been shown to be active against MCF-7 (human breast carcinoma), HT-29 (human colon carcinoma), A2780 (human ovarian carcinoma), and A2780cis (cisplatin-resistant human ovarian carcinoma) cell lines, with selected complexes' being more than three times as active as cisplatin against the A2780cis cell line. Selected complexes were also tested against the noncancerous ARPE-19 (retinal pigment epithelial cells) cell line, in order to evaluate the complexes selectivity for cancer cells.

One-pot synthesis of highly emissive dipyridinium dihydrohelicenes.

Condensation of a pyridyl-2-carbaldehyde derivative with 2-(bromoethyl)amine hydrobromide gave tetracyclic pyrido[1,2-a]pyrido[1',2':3,4]imidazo-[2,1-c]-6,7-dihydropyrazinium dications in excellent yields. Crystal structures and NOE data demonstrated the helical character of the dications, the dihedral angles between the two pyrido groups ranging from 28-45°. An intermediate in the synthesis was also characterized.

Activation and deactivation of a robust immobilized Cp*Ir-transfer hydrogenation catalyst: a multielement in situ X-ray absorption spectroscopy study.

A highly robust immobilized [Cp*IrCl2]2 precatalyst on Wang resin for transfer hydrogenation, which can be recycled up to 30 times, was studied using a novel combination of X-ray absorption spectroscopy (XAS) at Ir L3-edge, Cl K-edge, and K K-edge. These culminate in in situ XAS experiments that link structural changes of the Ir complex with its catalytic activity and its deactivation. Mercury poisoning and "hot filtration" experiments ruled out leached Ir as the active catalyst.

Synthesis and coordination chemistry of 1,1,1-tris-(pyrid-2-yl)ethane.

A new synthesis of 1,1,1-tris(pyrid-2-yl)ethane (L), and a survey of its coordination chemistry, are reported. The complexes [ML2](n+) (M(n+) = Fe(2+), Co(2+), Co(3+), Cu(2+) and Ag(+)), [PdCl2L] and [CuI(L)] have all been crystallographically characterised. Noteworthy results include an unusual square planar silver(i) complex [Ag(L)2]X (X(-) = NO3(-) and SbF6(-)); the oxidative fixation of aerobic CO2 by [CuI(L)] to yield [Cu2I(L)2(μ-CO3)]2[CuI3] and [Cu(CO3)(L)]; and, water/carbonato tape and water/iodo layer hydrogen bonding networks in hydrate crystals of two of the copper(ii) complexes.

Picolinamides as effective ligands for copper-catalysed aryl ether formation: structure-activity relationships, substrate scope and mechanistic investigations.

The use of picolinic acid amide derivatives as an effective family of bidentate ligands for copper-catalysed aryl ether synthesis is reported. A fluorine-substituted ligand gave good results in the synthesis of a wide range of aryl ethers. Even bulky phenols, known to be very challenging substrates, were shown to react with aryl iodides with excellent yields using these ligands.

Mechanistic and cytotoxicity studies of group IV β-diketonate complexes.

Group IV metal complexes have previously shown promise as novel anticancer agents. Here, we discuss the mechanistic and cytotoxic nature of a series of group IV β-diketonate coordination complexes. Clear evidence that the ligands are exchangeable on the metal centre and that the β-diketonate ligands can act as potential drug delivery vehicles of the group IV metal ions was obtained.

Copper catalysed Ullmann type chemistry: from mechanistic aspects to modern development.

Cu-catalysed arylation reactions devoted to the formation of C-C and C-heteroatom bonds (Ullmann-type couplings) have acquired great importance in the last decade. This review discusses the history and development of coupling reactions between aryl halides and various classes of nucleophiles, focusing mostly on the different mechanisms proposed through the years. Selected mechanistic investigations are treated more in depth than others.

Rhodium, iridium, and ruthenium half-sandwich picolinamide complexes as anticancer agents.

Novel rhodium, iridium, and ruthenium half-sandwich complexes containing (N,N)-bound picolinamide ligands have been prepared for use as anticancer agents. The complexes show promising cytotoxicities, with the presence, position, and number of halides having a significant effect on the corresponding IC50 values. One ruthenium complex was found to be more cytotoxic than cisplatin on HT-29 and MCF-7 cells after 5 days and 1 h, respectively, and it remains active with MCF-7 cells even under hypoxic conditions, making it a promising candidate for in vivo studies.

Synthesis and characterisation of tetramethylfulvene complexes of ruthenium.

Reactions of [RuCp*Cl2]2 with dibenzoylmethane and triethylamine, in either dichloromethane or toluene, produced the complexes [RuCl(η(6)-C5Me4CH2)(PhCOCCOPh)] (1) and [RuCl3(η(6)-C5Me4CH2)][RuCp*(C6H5CH3)] (2) respectively under mild conditions. Both compounds 1 and 2 are examples of an unusual tetramethylfulvene-ruthenium structure, obtained by deprotonation of the pentamethylcyclopentadienyl ligand, and were characterised by single-crystal X-ray diffraction.

A robust method to heterogenise and recycle group 9 catalysts.

This paper provides a viable, reproducible and robust method for immobilising hydroxyl tethered iridium-rhodium complexes. The materials have been shown to be both effective and recyclable in the process of catalytic transfer hydrogenation with minimal metal leaching.

Synthesis of iridium and ruthenium complexes with (N,N), (N,O) and (O,O) coordinating bidentate ligands as potential anti-cancer agents.

Several Ru-arene and Ir-Cp* complexes have been prepared incorporating (N,N), (N,O) and (O,O) coordinating bidentate ligands and have been found to be active against both HT-29 and MCF-7 cell lines. By incorporating a biologically active ligand into a metal complex the anti-cancer activity is increased.