Chien Ing Yeo

The influence of R substituents in triphenylphosphinegold(I) carbonimidothioates, Ph3PAu[SC(OR)=NPh] (R = Me, Et and iPr), upon in vitro cytotoxicity against the HT-29 colon cancer cell line and upon apoptotic pathways.

The Ph3PAu[SC(OR)=NPh], R=Me (1), Et (2) and iPr (3), compounds are significantly cytotoxic to the HT-29 cancer cell line with 1 being the most active. Based on human apoptosis PCR-array analysis, caspase activities, DNA fragmentation, cell apoptotic assays, intracellular reactive oxygen species (ROS) measurements and human topoisomerase I inhibition, induction of apoptosis is demonstrated and both the extrinsic and intrinsic pathways of apoptosis have been shown to occur. Compound 1 activates the p73 gene, whereas each of 2 and 3 activates the p53 gene. An additional apoptotic mechanism is exhibited by 2, that is, via the JNK/MAP pathway.

G2/M cell cycle arrest on HT-29 cancer cells and toxicity assessment of triphenylphosphanegold(I) carbonimidothioates, Ph3PAu[SC(OR)=NPh], R=Me, Et, and iPr, during zebrafish development.

Phosphanegold(I) thiolates, Ph3PAu[SC(OR)=NPh], R=Me (1), Et (2) and iPr (3), were previously shown to be significantly cytotoxic toward HT-29 cancer cells and to induce cell death by both intrinsic and extrinsic apoptotic pathways whereby 1 activated the p73 gene, and each of 2 and 3 activated p53; 2 also caused apoptotic cell death via the c-Jun N-terminal kinase/mitogen-activated protein kinase pathway. Apoptosis pathways have been further evaluated by mitochondrial cytochrome c measurements and annexin V screening, confirming apoptotic pathways of cell death. Cell cycle analysis showed the majority of treated HT-29 cells were arrested at the G2/M checkpoint after 24h; results of both assays were confirmed by changes in populations of relevant genes (PCR array analysis). Cell invasion studies showed inhibition of metastasis through Matrigel™ matrix to 17-22% cf. untreated cells. LC50 values were determined in zebrafish (8.36, 8.17, and 7.64μM for 1-3). Finally, the zebrafish tolerated doses of 1 and 2 up to 0.625μM, and 3 was tolerated at even higher doses of up to 1.25μM.

The importance of Au⋯π(aryl) interactions in the formation of spherical aggregates in binuclear phosphane gold(I) complexes of a bipodal thiocarbamate dianion: a combined crystallographic and computational study, and anti-microbial activity

Binuclear phosphanegold(I) complexes of a bipodal thiocarbamate dianion, (R3PAu)2L, R = Et (1), Ph (2) and Cy (3), where LH2 is {1,4-[MeOC(S)N(H)]2C6H4}, have been synthesised, and characterised spectroscopically (NMR and IR) and by X-ray crystallography. The gold atoms are linearly coordinated within a P-,S-donor set, and are oriented toward the central ring to form intramolecular Au⋯π(aryl) interactions, rather than the intramolecular Au⋯O interactions normally observed in mononuclear analogues. This phenomenon has been investigated by theory (LC-ωPBE-XDM) for 1 which revealed that the geometry optimised species with two Au⋯π(aryl) interactions is more stable by at least 12 kcal mol−1 compared to conformations having one or more Au⋯O interactions instead. The disk diffusion, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) methods were used to observe the inhibitory effect of complexes 1–3. The disk diffusion results demonstrated that 1 exhibited a broad spectrum of anti-bacterial activity toward 24 strains of Gram-positive and Gram-negative bacteria. By contrast, the anti-bacterial activity of 2 and 3 was limited to Gram-positive bacteria. Further evaluation showed that 1 exhibited marked bactericidal activity against B. cereus, B. subtilis, E. faecalis, L. monocytogenes, S. aureus, S. saprophyticus and methicillin resistant S. aureus cf. standard antibiotics tetracycline and chloramphenicol.

Supramolecular architectures sustained by arene-C–H…π(quasi-chelate ring) interactions in the crystal structures of copper(I) complexes

Abstract A review of the crystallographic literature is presented whereby structures featuring a quasi-six-membered chelate ring of the type {CuCl…HNCS} were evaluated for the presence of intermolecular C–H…π(quasi-chelate) interactions. These are shown to stabilise crystal structures leading to zero-, one-, two- and even three-dimensional architectures. Details of these interactions are described and a comparison to analogous interactions formed intramolecularly has been made. The C–H…π(quasi-chelate) interactions in these structures occur in one-third of structures where such contacts can potentially form.

1,3-Bis(2-chloro­phen­yl)thio­urea: a monoclinic polymorph

The title compound, C13H10Cl2N2S, represents a monoclinic polymorph of the previously reported orthorhombic form [Ramnathan et al. (1996 ▶). Acta Cryst. C52, 134–136]. The molecule is twisted with the dihedral angle between the benzene rings being 55.37 (7)°. The N—H atoms are syn to each other, which contrasts their anti disposition in the orthorhombic form. In the crystal, molecules assemble into zigzag chains along the c axis via N—H⋯S hydrogen bonds. Chains are connected into layers via C—H⋯Cl interactions, and these stack along the a axis.

A new monoclinic polymorph of N-(3-methyl­phen­yl)eth­oxy­carbo­thio­amide: crystal structure and Hirshfeld surface analysis

Two molecules comprise the asymmetric unit in the title thioamide molecule, each of which exists as the thioamide–thione tautomer. In the crystal, the molecules assemble via an eight-membered thioamide {⋯SCNH}2 synthon to form dimeric aggregates.

A non-solvated form of [(Z)-O-methyl-N-(2-methyl­phen­yl)­thio­carbamato-κS](tri­phenyl­phosphane-κP)gold(I): crystal structure and Hirshfeld surface analysis

A near linear geometry for the gold(I) atom defined by a P, S donor set is found in the title compound; an intramolecular Au⋯O short contact is noted. Supramolecular layers sustained by C—H⋯π and π—π interactions feature in the crystal.

The effects of phosphanegold(I) thiolates on the biological properties of Acanthamoeba castellanii belonging to the T4 genotype

BackgroundGold compounds have shown promise in the treatment of non-communicable diseases such as rheumatoid arthritis and cancer, and are considered of value as anti-microbial agents against Gram-negative and Gram-positive bacteria, and have anti-parasitic properties against Schistosoma mansoni, Trypanosoma brucei, Plasmodium falciparum, Leishmania infantinum, Giardia lamblia, and Entamoeba histolytica. They are known to affect enzymatic activities that are required for the cellular respiration processes.MethodsAnti-amoebic effects of phosphanegold(I) thiolates were tested against clinical isolate of A. castellanii belonging to the T4 genotype by employing viability assays, growth inhibition assays, encystation assays, excystation assays, and zymographic assays.ResultsThe treatment of A. castellanii with the phosphanegold(I) thiolates tested (i) had no effect on the viability of A. castellanii as determined by Trypan blue exclusion test, (ii) did not affect amoebae growth using PYG growth medium, (iii) did not inhibit cellular differentiation, and (iv) had no effect on the extracellular proteolytic activities of A. castellanii.ConclusionBeing free-living amoeba, A. castellanii is a versatile respirator and possesses respiratory mechanisms that adapt to various aerobic and anaerobic environments to avoid toxic threats and adverse conditions. For the first time, our findings showed that A. castellanii exhibits resistance to the toxic effects of gold compounds and could prove to be an attractive model to study mechanisms of metal resistance in eukaryotic cells.

μ3-Chlorido-μ2-chlorido-(μ3-pyrrolidine-1-carbo­dithio­ato-κ4S:S,S′:S′)tris­[(tri­ethyl­phosphane-κP)copper(I)]: crystal structure and Hirshfeld surface analysis

The dithiocarbamate ligand chelates one CuI atom and each S atom bridges a second CuI atom and thus, is tetracoordinate. The core of the molecule comprises Cu3Cl2S2 and defines seven corners of a distorted cube.

[N,N-Bis(2-hy­droxy­eth­yl)di­thio­carbamato-κ2S,S′]bis­(tri­phenyl­phosphane-κP)copper(I) chloro­form monosolvate: crystal structure, Hirshfeld surface analysis and solution NMR measurements

A tetrahedral CuP2S2 coordination geometry is found for the CuI ion in the title compound. The dithiocabamate ligand forms symmetric Cu—S bonds. In the crystal, supramolecular dimers of complex molecules are connected via eight-membered {⋯H—O⋯H—O}2 synthons. In addition, the chloroform molecule participates in Cl⋯π(arene) and S⋯Cl interactions.