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, [RhX2(L)(LH)] (where X = Cl or I), which incorporate two bidentate N-(3-halidophenyl)picolinamide ligands. The ligands have different binding modes in the complexes, whereby one is neutral and bound via N,N (LH) coordination, while the other is anionic and bound via N,O (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 trans isomers. NMR studies reveal the Rh(III) trans diiodido complexes remain stable in aqueous solution with no ligand exchange reported over 96 h. Chemosensitivity data against a range of cancer cell lines show two cytotoxic complexes, where L = N-(3-bromophenyl)picolinamide ligand. The results have been compared to the analogous Ru(III) complexes and overall highlight the Rh(III) trans diiodido complex to be ∼78× more cytotoxic than the analogous Rh(III) dichlorido complex, unlike the Ru(III) complexes which are equitoxic against all cell lines. Additionally, the Rh(III) trans diiodido complex is more selective toward cancerous cells, with selectivity index (SI) values >25-fold higher than cisplatin against colorectal carcinoma

Ammonium Pertechnetate in Mixtures of Trifluoromethanesulfonic Acid and Trifluoromethanesulfonic Anhydride

Ammonium pertechnetate reacts in mixtures of trifluoromethanesulfonic anhydride and trifluoromethanesulfonic acid under final formation of ammonium pentakis(trifluoromethanesulfonato)oxidotechnetate(V), (NH4)2[TcO(OTf)5]. The reaction proceeds only at exact concentrations and under the exclusion of air and moisture via pertechnetyl trifluoromethanesulfonate, [TcO3(OTf)], and intermediate TcVI species. 99Tc nuclear magnetic resonance (NMR) has been used to study the TcVII compound and electron paramagnetic resonance (EPR), 99Tc NMR and X-ray absorption near-edge structure (XANES) experiments indicate the presence of the reduced technetium species. In moist air, (NH4)2[TcO(OTf)5] slowly hydrolyses under formation of the tetrameric oxidotechnetate(V) (NH4)4[{TcO(TcO4)4}4] ⋅10 H2O. Single-crystal X-ray crystallography was used to determine the solid-state structures. Additionally, UV/Vis absorption and IR spectra as well as quantum chemical calculations confirm the identity of the species

Differential uranyl(v) oxo-group bonding between the uranium and metal cations from groups 1, 2, 4, and 12; a high energy resolution X-ray absorption, computational, and synthetic study

The uranyl(VI) ‘Pacman’ complex [(UO₂)(py)(H₂L)] A (L = polypyrrolic Schiff-base macrocycle) is reduced by Cp₂Ti(η²-Me₃SiC[triple bond, length as m-dash]CSiMe₃) and [Cp₂TiCl]₂ to oxo-titanated uranyl(V) complexes [(py)(Cp₂$Ti^{III}$OUO)(py)(H₂L)] 1 and [(ClCp₂$Ti^{IV}$OUO)(py)(H₂L)] 2. Combination of $Zr^{II}$ and $Zr^{IV}$ synthons with A yields the first $Zr^{IV}$–uranyl(V) complex, [(ClCp₂ZrOUO)(py)(H₂L)] 3. Similarly, combinations of $Ae^{0}$ and $Ae^{II}$ synthons (Ae = alkaline earth) afford the mono-oxo metalated uranyl(V) complexes [(py)₂(ClMgOUO)(py)(H₂L)] 4, [(py)₂(thf)₂(ICaOUO)(py) (H₂L)] 5; the zinc complexes [(py)₂(XZnOUO)(py)(H₂L)] (X = Cl 6, I 7) are formed in a similar manner. In contrast, the direct reactions of Rb or Cs metal with A generate the first mono-rubidiated and mono-caesiated uranyl(V) complexes; monomeric [(py)₃(RbOUO)(py)(H₂L)] 8 and hexameric [(MOUO)(py)(H₂L)]₆ (M = Rb 8b or Cs 9). In these uranyl(V) complexes, the pyrrole N–H atoms show strengthened hydrogen-bonding interactions with the endo-oxos, classified computationally as moderate-strength hydrogen bonds. Computational DFT MO (density functional theory molecular orbital) and EDA (energy decomposition analysis), uranium M₄ edge HR-XANES (High Energy Resolution X-ray Absorption Near Edge Structure) and 3d4f RIXS (Resonant Inelastic X-ray Scattering) have been used (the latter two for the first time for uranyl(V) in 7 (ZnI)) to compare the covalent character in the $U^{V}$–O and O–M bonds and show the 5f orbitals in uranyl(VI) complex A are unexpectedly more delocalised than in the uranyl(V) 7 (ZnI) complex. The $O_{exo}$–Zn bonds have a larger covalent contribution compared to the Mg–$O_{exo}$/Ca–$O_{exo}$ bonds, and more covalency is found in the U–$O_{exo}$ bond in 7 (ZnI), in agreement with the calculations

Ammonium Pertechnetate in Mixtures of Trifluoromethanesulfonic Acid and Trifluoromethanesulfonic Anhydride

Ammonium pertechnetate reacts in mixtures of trifluoromethanesulfonic anhydride and trifluoromethanesulfonic acid under final formation of ammonium pentakis(trifluoromethanesulfonato)oxidotechnetate(V), (NH$_{4}$)$_{2}$ [TcO(OTf) $_{5}$]. The reaction proceeds only at exact concentrations and under the exclusion of air and moisture via pertechnetyl trifluoromethanesulfonate, [TcO$_{3}$(OTf)], and intermediate Tc$^{VI}$ species. $^{99}$Tc nuclear magnetic resonance (NMR) has been used to study the Tc$^{VII}$ compound and electron paramagnetic resonance (EPR), $^{99}$Tc NMR and X-ray absorption near-edge structure (XANES) experiments indicate the presence of the reduced technetium species. In moist air, (NH$_{4}$)2[TcO(OTf)5] slowly hydrolyses under formation of the tetrameric oxidotechnetate(V) (NH$_{4}$)$_{4}$ [{TcO(TcO$_{4}$)$_{4}$}$_{4}$] ⋅10 H$_{2}$O. Single-crystal X-ray crystallography was used to determine the solid-state structures. Additionally, UV/Vis absorption and IR spectra as well as quantum chemical calculations confirm the identity of the species

Understanding the potential in vitro modes of action of bis(β‐diketonato) oxovanadium(IV) complexes

To understand the potential in vitro modes of action of bis(β-diketonato) oxovanadium(IV) complexes, nine compounds of varying functionality have been screened using a range of biological techniques. The antiproliferative activity against a range of cancerous and normal cell lines has been determined, and show these complexes are particularly sensitive against the lung carcinoma cell line, A549. Annexin V (apoptosis) and Caspase-3/7 assays were studied to confirm these complexes induce programmed cell death. While gel electrophoresis was used to determine DNA cleavage activity and production of reactive oxygen species (ROS), the Comet assay was used to determine induced genomic DNA damage. Additionally, Förster resonance energy transfer (FRET)-based DNA melting and fluorescent intercalation displacement assays have been used to determine the interaction of the complexes with double strand (DS) DNA and to establish preferential DNA base-pair binding (AT versus GC)

Pseudo electron-deficient organometallics: limited reactivity towards electron-donating ligands

YesHalf-sandwich metal complexes are of considerable interest in medicine, material, and nanomaterial chemistry. The design of libraries of such complexes with particular reactivity and properties is therefore a major quest. Here, we report the unique and peculiar reactivity of eight apparently 16-electron half-sandwich metal (ruthenium, osmium, rhodium, and iridium) complexes based on benzene-1,2-dithiolato and 3,6-dichlorobenzene-1,2-dithiolato chelating ligands. These electron-deficient complexes do not react with electron-donor pyridine derivatives, even with the strong σ-donor 4-dimethylaminopyridine (DMAP) ligand. The Ru, Rh, and Ir complexes accept electrons from the triphenylphosphine ligand (σ-donor, π-acceptor), whilst the Os complexes were found to be the first examples of non-electron-acceptor electron-deficient metal complexes. We rationalized these unique properties by a combination of experimental techniques and DFT/TDFT calculations. The synthetic versatility offered by this family of complexes, the low reactivity at the metal center, and the facile functionalization of the non-innocent benzene ligands is expected to allow the synthesis of libraries of pseudo electron-deficient half-sandwich complexes with unusual properties for a large range of applications

Fast, facile and solvent‐free dry melt synthesis of oxovanadium(IV) complexes: Simple design with high potency towards cancerous cells

YesA range of oxobis(phenyl‐1,3‐butanedione) vanadium(IV) complexes have been successfully synthesized from cheap starting materials and a simple and solvent‐free one‐pot dry‐melt reaction. This direct, straightforward, fast and alternative approach to inorganic synthesis has the potential for a wide range of applications. Analytical studies confirm their successful synthesis, purity and solid‐state coordination, and we report the complexes’ uses as potential drug candidates for the treatment of cancer. After a 24‐hour incubation of A549 lung carcinoma cells with the compounds, they reveal cytotoxicity values 11‐fold greater than cisplatin, and remain non‐toxic towards normal cell types. Additionally, the complexes are stable over a range of physiological pH values and show the potential for interactions with BSA.University of Bradford. Grant Number: Internal Research Development Fun

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. Additionally, the compounds have excellent selectivity for cancerous cells when tested against normal cell types, with selectivity ratios (SR) up to 35.6, contrary to that of cisplatin, which is neither selective nor specific for cancerous cells (SF=0.43 and SR=0.7–2.3). This work provides a preliminary understanding of the cytotoxicity of iridium compounds in the absence of p53 and has potential applications in treatment of cancers for which the p53 gene is absent or mutant

Solvated Actinoids: Methanol, Ethanol, and Water Adducts of Thorium and Uranium Tetrachloride

The solvent adducts of the tetravalent actinoid chlorides ThCl4 and UCl4 have been isolated with methanol as [ThCl4(MeOH)(4)] 1 and [UCl4(MeOH)(4)] 2, and with ethanol as [ThCl4(EtOH)(4)] 3 and [UCl4(EtOH)(4)] 4. In hydrochloric acid [ThCl2(H2O)(7)](Cl)(2)(H2O)(2) 5 forms, which is isotypic to the known [UCl2(H2O)(7)](Cl)(2)(H2O)(2) 6. The adducts have been analysed using SXRD, IR, CHN, TGA-MS and PXRD. The material can be isolated from saturated organic (1-4) or acidic aqueous (5-6) solutions, however, drying of the isolated material results in loss of HCl and the formation of oxide species, confirmed by the isolation of U3O8 after complete thermal decomposition