Separation of mercuric ions using 2-thienylbenzimidazole/cucurbit[7]uril/iron-oxide nanoparticles by pH control.

2-Thienylbenzimidazole (TBI)/cucurbit[7]uril (CB7) host-guest complex was used as a motif to significantly improve the turnover of γ-Fe3O4 magnetic nanoparticles for potential application in the separation of toxic mercuric ions in polluted water samples. The mechanism of restoring the original solid materials is based on applying the pH-controlled preferential binding of the CB7 host to the TBI guest. The analytical application of this concept has not been realized in the literature. The pH-controlled stimuli-responsive abilities were confirmed in aqueous solution by the three-order of magnitudes higher stability constant of the protonated TBIH+/CB7 complex (e.g., K = 4.8 × 108 M-1) when compared to neutral TBI/CB7 complex (e.g., K = 2.4 × 105 M-1), also manifested in an increase in pKa values by ~ 3.3 units in the ground state. The supramolecular interaction and adsorption on iron oxide nanoparticles (NPs) were also spectroscopically confirmed in the solid state. The excited-state lifetime values of TBI/CB7NPs increased upon lowering the pH values (e.g., from 0.6 to 1.3 ns) with a concomitant blue shift of ~ 25 nm because of polarity effects. The time-resolved photoluminescent behaviors of the final solids in the presence of CB7 ensured pH-driven reusable systems for capturing toxic mercuric ions. The study offers a unique approach for the controllable separation of mercury ions using an external magnet and in response to pH through preferential binding of the host to guest molecules on the top of magnetic surfaces.

Asymmetrically Coordinated Heterodimetallic Ir-Ru System: Synthesis, Computational, and Anticancer Aspects.

Herein, we present an unprecedented formation of a heterodinuclear complex [{(ppy)2IrIII}(µ-phpy){RuII(tpy)}](ClO4)2 {[1](ClO4)2} using terpyridyl/phenylpyridine as ancillary ligands and asymmetric phpy as a bridging ligand. The asymmetric binding mode (N∧N-∩-N∧N∧C-) of the phpy ligand in {[1](ClO4)2} is confirmed by 1H, 13C, 1H-1H correlated spectroscopy (COSY), high-resolution mass spectrum (HRMS), single-crystal X-ray crystallography techniques, and solution conductivity measurements. Theoretical investigation suggests that the highest occupied molecular orbital (HOMO) and the least unoccupied molecular orbital (LUMO) of [1]2+ are located on iridium/ppy and phpy, respectively. The complex displays a broad low energy charge transfer (CT) band within 450-575 nm. The time-dependent density functional theory (TDDFT) analysis suggests this as a mixture of metal-to-ligand charge transfer (MLCT) and ligand-to-ligand charge transfer (LLCT), where both ruthenium, iridium, and ligands are involved. Complex {[1](ClO4)2} exhibits RuIIIrIII/RuIIIIrIII- and RuIIIIrIII/RuIIIIrIV-based oxidative couples at 0.83 and 1.39 V, respectively. The complex shows anticancer activity and selectivity toward human breast cancer cells (IC50; MCF-7: 9.3 ± 1.2 µM, and MDA-MB-231: 8.6 ± 1.2 µM) over normal breast cells (MCF 10A: IC50 ≈ 21 ± 1.3 µM). The Western blot analysis and fluorescence microscopy images suggest that combined apoptosis and autophagy are responsible for cancer cell death.

Alkyl chain-modified cyclometalated iridium complexes as tunable anticancer and imaging agents.

Five mononuclear cyclometalated iridium complexes [1](PF6)-[5](PF6) were prepared using imidazole-based ligands of varying alkyl chain length. The complexes were characterised by various analytical techniques. The single crystal X-ray structures of [2](PF6), [3](PF6) and [4](PF6) revealed the expected distorted Oh structures around the metal centre; however, the chain length was found to play a crucial role in deciding the overall geometry. Theoretical investigations demonstrated that the HOMOs were mainly contributed by iridium and cyclometalated ligands, whereas the LUMOs were constituted from bpy/phen units. The complexes were found to be luminescent with a moderate emission quantum yield and lifetime in CH3CN. The in vitro growth inhibition assay of the complexes with a shorter alkyl chain ([4]+ and [5]+) displayed higher anticancer activity (IC50 < 0.5 µM) compared to the complexes with a longer alkyl chain ([1]+-[3]+) (IC50 < 30 µM) against human breast cancer (MCF-7) cells. The complexes [4]+ and [5]+ also displayed moderate cancer cell selectivity (∼3 times) over normal breast (MCF-10) cells. The flow cytometry assay and fluorescence microscopy analysis suggested that cellular accumulation was primarily responsible for the variation in anticancer activity. Interestingly, without possessing any anticancer activity or toxicity ((IC50 > 50 µM), the complex [1]+ mainly accumulated near the cell membrane outside the cell and displayed a clear image of the cell membrane. The light microscopy images and western blot analysis reveal that complex [4]+ induced combined apoptosis and paraptosis. Thus, tuning the anticancer activity and cellular imaging property mediated by the alkyl chain would be of great importance and would be useful in anticancer research.

Long-Lived Polypyridyl Based Mononuclear Ruthenium Complexes: Synthesis, Structure, and Azo Dye Decomposition.

Two mononuclear ruthenium complexes [(bpy)2RuIIL1/L2](ClO4)2 ([1]2+/[2]2+) (bpy-2,2' bipyridine, L1 = 2,3-di(pyridin-2-yl)pyrazino[2,3-f][1,10]phenanthroline) and L2 = 2,3-di(thiophen-2-yl)pyrazino[2,3-f][1,10]phenanthroline have been synthesized. The complexes have been characterized using various analytical techniques. The complex [1]2+ has further been characterized by its single crystal X-ray structure suggesting ruthenium is coordinating through the N donors of phenanthroline end. Theoretical investigation suggests that the HOMOs of both complexes are composed of pyridine and pyrazine unit of ligands L1 and L2 whereas the LUMOs are formed by the contribution of bipyridine units. The low energy bands at ∼480 nm of the complexes can be assigned as MLCT with partial contribution from ligand transitions, whereas the rest are ligand centered. The complexes have shown RuII/RuIII oxidation couples at E1/2 at 1.26 (70 mV) V and 1.28 (62 mV) V for [1]2+ and [2]2+ vs Ag/AgCl, respectively, suggesting no significant role of distal thiophene or pyridine units of the ligands. The complexes are emissive and display solvent dependent emission properties. Both complexes have shown highest emission quantum yield and lifetime in DMSO (ϕ = 0.05 and τavg = 460 ns and λmaxem at 620 nm for [1]2+; ϕ = 0.043 and τavg = 425 ns and λmaxem at 635 nm for [2]2+). Further, the long luminescent lifetime of these complexes has been utilized to generate reactive oxygen species for efficient azo dye decomposition.

Cyclometallated iridium complexes inducing paraptotic cell death like natural products: synthesis, structure and mechanistic aspects.

Six mononuclear Ir complexes (1-6) using polypyridyl-pyrazine based ligands (L1 and L2) and {[cp*IrCl(µ-Cl)]2 and [(ppy)2Ir(µ-Cl)]2} precursors have been synthesised and characterised. Complexes 1-5 have shown potent anticancer activity against various human cancer cell lines (MCF-7, LNCap, Ishikawa, DU145, PC3 and SKOV3) while complex 6 is found to be inactive. Flow cytometry studies have established that cellular accumulation of the complexes lies in the order 2 > 1 > 5 > 4 > 3 > 6 which is in accordance with their observed cytotoxicity. No changes in the expression of the proteins like PARP, caspase 9 and beclin-1, Atg12 discard apoptosis and autophagy, respectively. Overexpression of CHOP, activation of MAPKs (P38, JNK, and ERK) and massive cytoplasmic vacuolisation collectively suggest a paraptotic mode of cell death induced by proteasomal dysfunction as well as endoplasmic reticulum and mitochondrial stress. An intimate relationship between p53, ROS production and extent of cell death has also been established using p53 wild, null and mutant type cancer cells.

A dinuclear [{(p-cym)Ru(II)Cl}2(µ-bpytz˙(-))](+) complex bridged by a radical anion: synthesis, spectroelectrochemical, EPR and theoretical investigation (bpytz = 3,6-bis(3,5-dimethylpyrazolyl)1,2,4,5-tetrazine; p-cym = p-cymene).

The reaction of the chloro-bridged dimeric precursor [{(p-cym)Ru(II)Cl}(µ-Cl)]2 (p-cym = p-cymene) with the bridging ligand 3,6-bis(3,5-dimethylpyrazolyl)-1,2,4,5-tetrazine (bpytz) in ethanol results in the formation of the dinuclear complex [{(p-cym)Ru(II)Cl}2(µ-bpytz˙(-))](+), [1](+). The bridging tetrazine ligand is reduced to the anion radical (bpytz˙(-)) which connects the two Ru(II) centres. Compound [1](PF6) has been characterised by an array of spectroscopic and electrochemical techniques. The radical anion character has been confirmed by magnetic moment (corresponding to one electron paramagnetism) measurement, EPR spectroscopic investigation (tetrazine radical anion based EPR spectrum) as well as density functional theory based calculations. Complex [1](+) displays two successive one electron oxidation processes at 0.66 and 1.56 V versus Ag/AgCl which can be attributed to [{(p-cym)Ru(II)C}2(µ-bpytz˙(-))](+)/[{(p-cym)Ru(II)Cl}2(µ-bpytz)](2+) and [{(p-cym)Ru(II)Cl}2(µ-bpytz)](+)/[{(p-cym)Ru(III)Cl}2(µ-bpytz)](2+) processes (couples I and II), respectively. The reduction processes (couple III-couple V), which are irreversible, likely involve the successive reduction of the bridging ligand and the metal centres together with loss of the coordinated chloride ligands. UV-Vis-NIR spectroelectrochemical investigation reveals typical tetrazine radical anion containing bands for [1](+) and a strong absorption in the visible region for the oxidized form [1](2+), which can be assigned to a Ru(II) → π* (tetrazine) MLCT transition. The assignment of spectroscopic bands was confirmed by theoretical calculations.