The ability of silver(I) thiocyanate 4-methoxyphenyl phosphine to induce apoptotic cell death in esophageal cancer cells is correlated to mitochondrial perturbations.

First generation silver(I) phosphines have garnered much interest due to their vast structural diversity and promising anticancer activity. Increasing incidences of cancer, side-effects to chemotherapeutic agents and redevelopment of tumors due to resistance prompts the exploration of alternative compounds showing anticancer activity. This study revealed the effective induction of cell death by a silver(I) thiocyanate 4-methoxyphenyl phosphine complex in a malignant esophageal cell line. Apoptotic cell death was confirmed in treated cells. Moreover, mitochondrial targeting via the intrinsic cell death pathway was evident due to low levels of ATP, altered ROS activity, mitochondrial membrane depolarization, cytochrome c release and caspase-9 cleavage. The complex displayed low cytotoxicity towards two human non-malignant, skin and kidney, cell lines. The findings reported herein give further insight into the selective targeting of silver(I) phosphines and support our belief that this complex shows great promise as an effective chemotherapeutic drug.

Synergistic Effects of Gold-Palladium Nanoalloys and Reducible Supports on the Catalytic Reduction of 4-Nitrophenol.

Herein we report on the catalytic activity of mesoporous nickel, iron, cerium, cobalt, and manganese oxides prepared using KIT-6 as a hard template via evaporation-assisted precipitation. The mesoporous metal oxides (MMOs) were characterized and used as heterogeneous catalysts in the reduction of 4-nitrophenol (4-Nip) by sodium borohydride (BH4-). Furthermore, polyamidoamide (PAMAM) dendrimers were used to synthesize gold-palladium nanoalloy particles. The size of AuPd/PAMAM was found to be 3.5 ± 0.8 nm in diameter before being immobilized on the aforementioned mesoporous metal oxides and used as catalysts in the reduction of 4-Nip. Prior to catalytic evaluation, the reduction profiles of the mesoporous metal oxides were investigated by hydrogen-temperature-programmed reduction (H2-TPR) and showed that mesoporous metal oxides can be easily reduced at lower temperatures and that the immobilization of gold-palladium nanoalloy particles lowers their reduction temperatures. Mesoporous cobalt and manganese oxides showed catalytic activity toward 4-Nip reduction, and the activity was enhanced after immobilization of the gold-palladium nanoalloys. Isolation of nanoparticles activity was achieved by immobilization of the gold-palladium nanoalloys on the inert silica support. From this we postulated an electron relay mechanism for the reduction of 4-nitrophenol. With the use of power rate law we showed that 4-Nip reduction follows pseudo-first-order kinetics.

Catalytic Behavior of Different Sizes of Dendrimer-Encapsulated Au(n) Nanoparticles in the Oxidative Degradation of Morin with H2O2.

Different sizes of icosahedral-like dendrimer-encapsulated Au nanoparticles (Au55- and Au147-DENs) were prepared in the presence of generation 6 amine-terminated dendrimers (G6-PAMAM-NH2) as a template. The synthesis is carried out by the complexation of a Au metal precursor (AuHCI4) with the tertiary amine groups within the dendrimer framework. The addition of excess reducing agent, NaBH4, results in the formation of Au nanoparticles encapsulated within the dendrimer cavities. The as-prepared catalysts were characterized using UV-visible (UV-vis) spectroscopy, high-resolution transmission electron microscopy (HRTEM), energy-dispersive X-ray analysis (EDX), and Fourier transform infrared (FTIR). The average sizes of Au55- and Au147-DENs were determined to be 1.7 ± 0.4 and 2.0 ± 0.3 nm, respectively. The catalytic activity of these Au-DEN catalysts was evaluated in the oxidative decomposition of morin by H2O2. Since morin has a maximum absorption band at λ 410 nm at pH 10, this catalyzed oxidation process was monitored by time-resolved UV-vis spectroscopy. The catalytic activities of these two catalysts were compared by fitting the kinetic data to the Langmuir-Hinshelwood model. This model allows the determination of adsorption constants of both morin (K(morin)) and H2O2 (K(H2O2)) on the catalyst surface. A full kinetic study for this Au-DEN-catalyzed oxidative degradation of morin is reported.

The effect of 1:2 Ag(I) thiocyanate complexes in MCF-7 breast cancer cells.

There is much interest currently in the design of metal compounds as drugs and various metal compounds are already in clinical use. These include gold(I) compounds such as auranofin and the anti-cancer platinum(II) complex, cisplatin. Bis-chelated gold(I) phosphine complexes have also shown great potential as anticancer agents, however, their efficacy has been limited by their high toxicity. In this study, silver(I) thiocyanate compounds linked to four specific ligands, were synthesized and characterized. These silver-phosphine adducts included [AgSCN{P(4-MeC6H4)3}2]2 (1); [AgSCN{P(4-ClC6H4)3}2]2 (2); [AgSCN{P(4-MeOC6H4)3}2]2 (3); [AgSCN(PPh3)2]2 (4). The compounds were found to be toxic to MCF-7 breast cancer cells while the ligands on their own were not toxic. Our findings further indicate that the silver(I) phosphine compounds induce apoptotic cell death in these breast cancer cells. In addition, the compounds were not toxic to nonmalignant fibroblast cells at the IC50 concentrations. This is an indication that the compounds show selectivity towards the cancer cells.

The induction of cell death by phosphine silver(I) thiocyanate complexes in SNO-esophageal cancer cells.

Esophageal cancer is one of the least studied cancers and is found to be prominent in black South African males. It is mainly diagnosed in the late stages, and patients tend to have a low 5-year survival rate of only 10%. Silver is generally used as an antimicrobial agent, with limited reports on anticancer studies. In this study, dimeric silver(I) thiocyanate complexes were used containing a variation of 4-substitued triphenylphosphines, including [AgSCN(PPh(3))(2)](2) (1), [AgSCN{P(4-MeC(6)H(4))(3)}(2)](2) (2), [AgSCN{P(4-FC(6)H(4))(3)}(2)](2) (3) and [AgSCN{P(4-ClC(6)H(4))(3)}(2)](2) (4). All four complexes, with their respective phosphine ligands, PPh(3) (L1), P(4-MeC(6)H(4))(3) (L2), P(4-FC(6)H(4))(3) (L3) and P(4-ClC(6)H(4))(3) (L4), were subjected to in vitro toxicity studies in SNO-esophageal cancer cells, using an alamarBlue(®) assay. Morphological changes, including blebbing and apoptotic body formation, were observed. Phosphatidylserine externalization, a marker of apoptosis, was quantified by flow cytometry. The phosphine ligands L1-L4, on their own, had minimal effect on the malignant while complexes 1-4 resulted in significant cell death. A 10x decreased concentration of these complexes had similar effects than cisplatin, used as the positive control. These complexes show promise as anticancer agents.

Preparation of well-defined dendrimer encapsulated ruthenium nanoparticles and their evaluation in the reduction of 4-nitrophenol according to the Langmuir-Hinshelwood approach.

This study discusses the preparation of various sized dendrimer encapsulated ruthenium nanoparticles (RuDEN) with the use of the generation 4 (G4), generation 5 (G5), and generation 6 (G6) hydroxyl-terminated poly(amidoamine) (PAMAM-OH) dendrimers as templating agents. The size of the nanoparticles ranges from 1.1 to 2.2 nm. These catalysts were fully characterized using UV/vis spectrophotometry, infrared (IR) spectroscopy, and transmission electron microscopy (TEM). The RuDEN catalysts were evaluated in the reduction of 4-nitrophenol (4NP) in the presence of sodium borohydride (BH4(-)) for various concentrations of either. The kinetic data obtained were modeled to the Langmuir-Hinshelwood equation. The model allows the relation of the apparent rate constant to the total surface area S of the nanoparticle, the kinetic constant k which is related to the rate-determining step, and the adsorption constants K(4NP) and K(BH4) for 4NP and borohydride, respectively. These parameters were calculated for each of the RuDENs, proving the Langmuir-Hinshelwood model to be suitable for the kinetic evaluation of RuDENs in the catalytic reduction of 4NP.

Silver(I) Bromide Phosphines Induce Mitochondrial-Mediated Apoptosis in Malignant Human Colorectal Cells.

Due to its emerging resistance to current therapies, colon cancer remains one of the most difficult types of cancer to treat. Silver, a non-invasive metal, is well-known for its antimicrobial and anti-cancer properties. Two novel silver(I) phosphine complexes, [silver(I) diphenyl-2-pyridylphosphine]Br (1) and [silver(I) is 4-(dimethylamino)phenyldiphenylphosphine]Br (2), were synthesized and characterized by elemental analysis, infrared spectroscopy, and nuclear magnetic resonance (1H, 13C, 31P). To assess the complexes' potentials as antiproliferative agents, experiments were conducted on human colorectal cancer cells (HT-29) in vitro. The evaluation involved the analysis of morphological changes, the performance of an alamarBlue® proliferation assay, and the undertaking of flow cytometric analyses to detect mitochondrial alterations. Complex 1 displayed superior selectivity and significant inhibitory effects on malignant HT-29 cells while exhibiting minimal toxicity towards two non-malignant HEK-293 and MRHF cells. Moreover, after 24 h of treatment, complex 1 (IC50, 7.49 µM) demonstrated higher efficacy in inhibiting cell proliferation compared with complex 2 (IC50, 21.75 µM) and CDDP (IC50, 200.96 µM). Flow cytometric studies indicated that complex 1 induced regulated cell death, likely through mitochondrial-mediated apoptosis. Treatment with complex 1 induced morphological changes indicative of apoptosis, which includes membrane blebbing, PS externalization, increased levels of reactive oxygen species (ROS) and mitochondrial membrane depolarization (ΔΨm). These observations suggest that complex 1 targets the mitochondria and holds promise as a novel metal-based anti-cancer therapeutic for the selective treatment of colorectal cancer.

(Acetyl-acetonato-κ(2)O,O')carbon-yl[tris-(naphthalen-1-yl)phosphane-κP]rhodium(I) acetone hemisolvate.

The title compound, [Rh(C(5)H(7)O(2))(C(30)H(21)P)(CO)]·0.5C(3)H(6)O, has two different complex molecules in the asymmetric unit, with the Rh(I) atoms in slightly distorted square-planar coordination environments. The molecules are packed as two monomeric mol-ecules with one acetone solvent mol-ecule sitting at the centre.

trans-Dichloridobis{dicyclo-hex-yl[4-(dimethyl-amino)-phen-yl]phosphane-κP}platinum(II) dichloro-methane disolvate.

In the title complex, trans-[PtCl2{P(C6H11)2(4-Me2NC6H4)}2]·2CH2Cl2, the Pt(II) atom is located on an inversion centre, resulting in a trans-square-planar geometry. Important geometric parameters are the Pt-P and Pt-Cl bond lengths of 2.3258 (6) and 2.3106 (6) Å, respectively, and the P-Pt-Cl angles of 89.64 (2) and 90.36 (2)°. The effective cone angle for the dicyclo-hex-yl[4-(dimethyl-amino)-phen-yl]phosphane unit was calculated to be 164°. The compound crystallizes with two dichloro-methane solvent mol-ecules; one of which is severely disordered and was treated using the SQUEEZE routine in PLATON [Spek (2009 ▶). Acta Cryst. D65, 148-155].

(Acetyl-acetonato-κ(2)O,O')[(2-bromo-phen-yl)diphenyl-phosphane-κP]carbonyl-rhodium(I).

In the title compound, [Rh(C(5)H(7)O(2))(C(18)H(14)BrP)(CO)], the Rh(I) atom adopts a slightly distorted square-planar geometry involving two O atoms [Rh-O = 2.077 (2) and 2.033 (2) Å] of the acetyl-acetonate ligand, one carbonyl C atom [Rh-C = 1.813 (2) Å] and one P atom [Rh-P = 2.242 (5) Å] of the PPh(2)(2-BrC(6)H(4)) phosphane ligand. Difference electron density maps indicate a disorder of the Br atom over two positions in an approximate 0.95:0.05 ratio. However, this disorder could not be resolved satisfactorily with the present data.

(Acetyl-acetonato-κ(2)O,O')carbon-yl[tris-(4-chloro-phen-yl)phosphane-κP]rhodium(I).

The title compound, [Rh(C(5)H(7)O(2))(C(18)H(12)Cl(3)P)(CO)], contains the bidentate acetyl-acetonate ligand coordinated to the Rh(I) atom, forming a chelate ring [Rh-O = 2.0327 (15) and 2.0613 (14) Å]. The Rh(I) atom is additionally coordinated by one P [Rh-P = 2.2281 (6) Å] and one carbonyl C [Rh-C = 1.812 (2) Å] atom, resulting in a slightly distorted square-planar geometry. The mol-ecules are packed to minimize steric hindrance with the phosphanes positioned above and below the slightly distorted square geometrical plane.

trans-Dichloridobis[dicyclo-hex-yl(2,4,6-trimethyl-phen-yl)phosphane-κP]palladium(II).

The title compound, [PdCl(2)(C(21)H(33)P)(2)], forms a monomeric complex with a trans-square-planar coordination geometry about the Pd(II) atom which lies on an inversion centre. The Pd-P bond lengths are 2.3760 (13) Å, while the Pd-Cl bond lengths are 2.3172 (14) Å. The observed structure was found to be closely related to that of trans-dichloridobis[dicyclo-hex-yl(phen-yl)phosphane-κP]palladium(II), [PdCl(2){P(C(6)H(11))(2)(C(6)H(5))}(2)] [Burgoyne et al. (2012 ▶). Acta Cryst. E68, m404].

1-(Thio-phen-2-yl)-N-(4-{(E)-[(thio-phen-2-yl)meth-yl]imino-meth-yl}benzyl-idene)methanamine.

The title compound C(18)H(16)N(2)S(2), crystallizes with two independent half-mol-ecules in the asymmetric unit, in one of which the thio-phene rings are disordered in a 0.67:0.33 ratio. Each independent mol-ecule lies across a crystallographic centre of symmetry. The dihedral angle between central (half) benzene ring and the thiophene ring is 11.82°.

trans-Dichloridobis[dicyclo-hex-yl(phen-yl)phosphane-κP]palladium(II).

The title compound, [PdCl(2){P(C(6)H(11))(2)(C(6)H(5))}(2)], forms a monomeric complex with a trans-square-planar geometry. The Pd-P bond lengths are 2.3343 (5) Å, as the Pd atom lies on an inversion centre, while the Pd-Cl bond lengths are 2.3017 (4) Å. The observed structure was found to be closely related to [PdCl(2){P(C(6)H(11))(3)}(2)] [Grushin et al. (1994 ▶). Inorg. Chem.33, 4804-4806], [PdBr(2){P(C(6)H(11))(3)}(2)] [Clarke et al. (2003 ▶). Dalton Trans. pp. 4393-4394] and [PdCl(2)P(C(6)H(11))(2)(C(7)H(7))}(2)] [Vuoti et al. (2008 ▶). Eur. J. Inorg. Chem. pp. 397-407] (C(6)H(11) is cyclo-hexyl and C(7)H(7) is o-tol-yl). One of the cyclo-hexyl rings is disordered with the phenyl ring in a 0.587 (9):413 (9) ratio. Five long-range C-H⋯Cl inter-actions were observed within the structure.

trans-Bis[(2-bromo-phen-yl)diphenyl-phosphane-κP]carbonyl-chlorido-rhodium(I).

The title compound, trans-[RhCl(C(18)H(14)BrP)(2)(CO)], has a slightly disordered square-planar geometry with the Rh ion(I) situated on an inversion the centre and carbon-yl-chloride disorder observed as a result of the crystallographic inversion symmetry. Selected geometric parameters include: Rh-P = 2.3430 (8) Å, Rh-Cl = 2.434 (3) Å, Rh-C = 1.722 (8) Å, P-Rh-P = 180.00 (3)°, P-Rh-Cl = 95.40 (7)°, 84.60 (7)° and Rh-C-O = 177.9 (8)°.

trans-Carbonyl-chloridobis[diphen-yl(4-vinyl-phen-yl)phosphane-κP]rhodium(I).

In the title compound, trans-[RhCl(C(20)H(17)P)(2)(CO)], the Rh(I) atom is situated on a center of symmetry, resulting in a statistical 1:1 disorder of the chloride [Rh-Cl = 2.383 (2) Å] and carbonyl [Rh-C = 1.752 (7) Å] ligands. The distorted trans square-planar environment is completed by two P atoms [Rh-P = 2.3251 (4) Å] from two diphen-yl(4-vinyl-phen-yl)phosphane ligands. The vinyl group is disordered over two sets of sites in a 0.668 (10):0.332 (10) ratio. The crystal packing exhibits weak C-H⋯Cl and C-H⋯O hydrogen bonds and π-π inter-actions between the phenyl rings of neighbouring mol-ecules, with a centroid-centroid distance of 3.682 (2) Å.

trans-Dichloridobis[diphen-yl(thio-phen-2-yl)phosphane-κP]palladium(II).

The title compound, trans-[PdCl(2)(C(16)H(13)PS)(2)], forms a monomeric complex with a trans-square-planar geometry. The Pd-P bond lengths are 2.3387 (11) Å, as the Pd atom lies on an inversion point, while the Pd-Cl bond lengths are 2.2950 (12) Å.

cis-Dichloridobis[tris-(4-chloro-phen-yl)phosphane-κP]platinum(II) acetonitrile monosolvate.

The title compound, [PtCl(2)(C(18)H(12)Cl(3)P)(2)]·C(2)H(3)N, packs as monomeric units with a square-planar geometry around the Pt(II) atom. The two tris-(4-chloro-phen-yl)phosphane ligands are coordinated in a cis orientation, with P-Pt-P and Cl-Pt-Cl angles of 99.36 (2) and 88.02 (2)°, respectively. In the crystal, C-H⋯N inter-actions are observed between the phenyl rings and the acetonitrile solvent mol-ecules.

(Acetyl-acetonato-κ(2)O,O')carbon-yl[dicyclo-hex-yl(2,6-diisopropyl-phen-yl)phosphane-κP]rhodium(I).

In the title compound, [Rh(C(5)H(7)O(2)){C(12)H(17)P(C(6)H(11))(2)}(CO)], the Rh(I) atom is coordinated by one carbonyl C, one P and two O atoms, forming a slighlty distorted square-planar configuration.

catena-Poly[[(benzyl-diphenyl-phosphine-κP)silver(I)]-µ-nitrato-κ2 O:O'-[(benzyl-diphenyl-phosphine-κP)silver(I)]-µ-nitrato-κ4 O,O':O',O''].

The structure of the title complex, [Ag2(NO3)2(C19H17P)2] n , reveals a chain emanating from the coordination of one phosphine ligand to each silver(I) cation, as well as the bis-monodentate coordination of a bridging nitrato ligand (per Ag atom) and the bis-bidentate coordination of another bridging nitrato ligand (per Ag atom). The distorted four-coordinate Ag atoms are characterized by bonding angles that notably deviate from the ideal tetra-hedral shape.