SAR Study on Thiolato-Bridged Triosmium Carbonyl Clusters: Higher Reactivity Does Not Equal Higher Antiproliferative Activity.

A structure-activity relationship study on triosmium clusters of the general formula Os(μ-H)(μ-SCHX)(CO) (, where X = -, - or -NH; -, - or - OH; p-H, -Br, -NO, -COOH or -CHCOOH) show that their antiproliferative activity is through the cluster core, and the nature and position of the phenyl ring substituent X shows a significant impact on the activity. Clusters with an electron-withdrawing group are more reactive but are thus quickly consumed through reaction with serum, while those with an electron-donating group persists sufficiently to enter the cells and result in higher antiproliferative activity. Interestingly, -substituted clusters and those with lipophilicity >6.

Group VIII Metal Carbonyl Cluster-Boronic Acid Conjugates: Cytotoxicity and Mode of Action Studies.

A set of metal carbonyl cluster-boronic acid conjugates of the group VIII metals (Fe, Ru, and Os) were synthesized and their antiproliferative effects measured against two breast cancer cell lines (MCF-7 and MDA-MB-231) and a noncancerous breast epithelial (MCF-10A) cell line. The cytotoxicity followed the order Ru > Os > Fe for the MDA-MB-231 cells, although the latter two exhibited similar cytotoxicity against MCF-7 and MCF-10A cells. The osmium species {Os(CO)(μ-H)[μ-SCH--B(OH)]} () could be chemically oxidized to its hydroxy analogue [Os(CO)(μ-H)(μ-SCH -OH)] (), which showed comparable cytotoxicity.

Inhibition of Thioredoxin Reductase by Triosmium Carbonyl Clusters.

Tumor cells are characterized by increased reactive oxygen species production in parallel with an enhanced antioxidant system to avoid oxidative damage. The inhibition of antioxidant systems is an effective way to kill cancer cells, and the thioredoxin system or, more specifically, the cytosolic selenocysteine-containing enzyme thioredoxin reductase (TrxR) has become an interesting target for cancer therapy. We show here that the known cytotoxic and apoptosis-inducing osmium carbonyl cluster Os(CO)(NCCH) () is a nonsubstrate inhibitor of mammalian TrxR, with an IC of 5.

A comparative study on atomically precise Au nanoclusters as catalysts for the aldehyde-alkyne-amine (A) coupling reaction: ligand effects on the nature of the catalysis and efficiency.

Atomically precise Au nanoclusters stabilized by stibines catalyze the aldehyde-alkyne-amine coupling reaction more efficiently than those stabilized by thiols or phosphines. The nature of the catalytic activity is also different, and may be attributed to the weaker coordinating ability of the stibine ligands.

Stibine-protected Au nanoclusters: syntheses, properties and facile conversion to GSH-protected Au nanocluster.

Monostibine-protected ionic Au nanoclusters, namely, [Au(L)(Cl)][Cl] (L= SbPh, ·Cl; Sb(-tolyl), ·Cl) were prepared by the direct reduction of Au(L)Cl with NaBH in dichloromethane. Anion exchange with ·Cl afforded [Au(SbPh)(Cl)][X] (X = PF, ·PF; BPh, ·BPh). All these have been characterized by multinuclear NMR, ESI-MS and UV-Vis spectroscopy.

Organometallic-Constructed Tip-Based Dual Chemical Sensing by Tip-Enhanced Raman Spectroscopy for Diabetes Detection.

Tip-enhanced Raman spectroscopy (TERS) is capable of probing specific molecular information with high sensitivity, but dual chemical sensing remains a challenge. Another major hindrance to TERS chemical detection in biosamples such as blood is the interference from the strong absorptions of biomolecules. Herein, we report the preparation of an organometallic-conjugated TERS tip.

Embedding a Ruthenium-Based Structural Mimic of the [Fe]-Hydrogenase Cofactor into Papain.

We describe the synthesis of the ruthenacyclic carbamoyl complexes [Ru(2-NHC(O)CHNMe)(CO)( o,o-Me-CHS)(L)] (L = HO or MeCN), which have a labile water or acetonitrile ligand at their sixth coordination sites. Steric bulk around the ruthenium center is essential in preventing isomerization and dimerization, and embedding within papain can be achieved via coordination of its sole free cysteine residue. The observed chemistry parallels that of the natural [Fe]-hydrogenase.

Structural Mimics of the [Fe]-Hydrogenase: A Complete Set for Group VIII Metals.

A set of structural mimics of the [Fe]-hydrogenase active site comprising all the group VIII metals, viz., [M(2-NHC(O)CHN)(CO)(2-S-CHN)], has been synthesized. They exist as a mixture of isomers in solution, and the relative stability of the isomers depends on the nature of the metal and the substituent at the 6-position of the pyridine ligand.

High nuclearity carbonyl clusters as near-IR contrast agents for photoacoustic in vivo imaging.

High nuclearity carbonyl clusters of ruthenium and osmium are found to exhibit good photoacoustic (PA) activity in the near-IR (NIR) region. Their potential as PA contrast agents for full body imaging has been demonstrated for the first time with mice; intravenous administration of the osmium carbonyl cluster Na[Os(μ-C)(CO)] afforded up to a four-fold enhancement of the PA signal in various tissues. The cluster exhibits low toxicity, high stability and superior PA stability compared to the clinically approved NIR dye, indocyanine green.

Osmocenyl-tamoxifen derivatives target the thioredoxin system leading to a redox imbalance in Jurkat cells.

The synthesis and the biological effects of two ferrocifen analogs in the osmium series, namely the monophenolic complex 1, the tamoxifen-like complex 2 and their oxidized quinone methide (QM) derivatives, 1-QM and 2-QM, are reported. Inhibition of purified thioredoxin reductase (TrxR) is observed with 1 and 2 only after their enzymatic oxidation by the hydrogen peroxide/horseradish peroxidase (H2O2/HRP) system with IC50 of 2.4 and 1.

Vibrational spectroscopy of metal carbonyls for bio-imaging and -sensing.

Transition metal carbonyls exhibit strong CO absorptions in the 2200-1800 cm(-1) region, which is free of interference from other functional groups. This feature has led to their applications in bio-imaging and -sensing, in particular through mid-IR, Raman and more recently, surface-enhanced Raman spectroscopy (SERS). Their use in mid-IR quantitative sensing based on vibrational intensities, and chemical sensing based on frequency shifts and vibrational lifetimes, is reviewed.

A rapid and label-free SERS detection method for biomarkers in clinical biofluids.

A metal carbonyl-functionalized nanostructured substrate can be used in a rapid and simple assay for the detection of A1AT, a potential biomarker for bladder cancer, in clinical urine samples. The assay involves monitoring changes in the carbonyl stretching vibrations of the metal carbonyl via surface-enhanced Raman spectroscopy (SERS). These vibrations lie in the absorption spectral window of 1800-2200 cm(-1), which is free of any spectral interference from biomolecules.

[Cp*IrCl2]2 catalyzed formation of 2,2'-biindoles from 2-ethynylanilines.

[Cp*IrCl2]2 catalyzes the cyclization of 2-ethynylanilines to 2,2'-biindoles via intramolecular hydroamination. A reaction pathway has been proposed on the basis of deuterium labeling experiments and computational studies.

Organometallic carbonyl clusters: a new class of contrast agents for photoacoustic cerebral vascular imaging.

We report, for the first time, the use of a water-soluble organometallic compound as a stable, reliable and high-contrast photoacoustic contrast agent. This gives a significantly higher contrast than that achievable with alternatives such as single-walled carbon nanotubes. Image enhancement of the rat cerebral cortex vasculature was observed using in vivo dark-field photoacoustic microscopy.

Cytotoxic triosmium carbonyl clusters: a structure-activity relationship study.

A structure-activity relationship (SAR) study of the triosmium carbonyl cluster Os3 (CO)10 (NCCH3 )2 was carried out with a series of clusters of the general formula Os3 (CO)12-n Ln , cationic osmium clusters and a hemi-labile maltolato-Os cluster. The SAR results showed that good solubility in DMSO and at least one vacant site are required for cytotoxicity. In vitro evaluation of these new compounds showed that some are selectively active against estrogen receptor (ER)-independent MDA-MB-231 breast cancer cell lines relative to ER-dependent MCF-7 breast cancer cells, suggesting that the compounds have a different biological target specific to MDA-MB-231 cells.

A transition metal carbonyl probe for use in a highly specific and sensitive SERS-based assay for glucose.

A triosmium carbonyl cluster-boronic acid conjugate is used as a secondary carbohydrate probe in a SERS-based assay. The assay does not require conjugation of the metal carbonyl probe to a SERS-active species, and it utilizes the CO stretching vibrations of the metal carbonyl, which lies in a silent region of the SERS spectrum (1800-2200 cm(-1)), for quantification. High selectivity for glucose over fructose and galactose is obtained, and a human urine sample doped with glucose is detected accurately.

Ternary copper(II)-polypyridyl enantiomers: aldol-type condensation, characterization, DNA-binding recognition, BSA-binding and anticancer property.

Chiral enantiomers [Cu(phen)(L-threo)(H2O)]NO3 1 and [Cu(phen)(D-threo)(H2O)]NO3 2 (threo = threoninate) underwent aldol-type condensation with formaldehyde, with retention of chirality, to yield their respective enantiomeric ternary copper(II) complexes, viz. L- and D-[Cu(phen)(5MeOCA)(H2O)]NO3·xH2O (3 and 4; phen = 1,10-phenanthroline; 5MeOCA = 5-methyloxazolidine-4-carboxylate; x = 0-3) respectively. These chiral complexes were characterized by FTIR, elemental analysis, circular dichroism, UV-Visible spectroscopy, fluorescence spectroscopy (FL), molar conductivity measurement, ESI-MS and X-ray crystallography.

Metal carbonyl-gold nanoparticle conjugates for live-cell SERS imaging.

Conjugates of organometallic osmium carbonyl clusters and gold nanoparticles show a strong carbonyl signal in surface-enhanced Raman spectroscopy. The ease of bio-functionalization and the high stability and good dispersibility in aqueous solution make these conjugates excellent candidates for biomedical applications, as demonstrated by live-cell imaging with the carbonyl signals of OM-NP(PEG)-L conjugates.

Biological and cytoselective anticancer properties of copper(II)-polypyridyl complexes modulated by auxiliary methylated glycine ligand.

A series of ternary copper(II)-1,10-phenanthroline complexes with glycine and methylated glycine derivatives, [Cu(phen)(aa)(H(2)O)]NO(3)·xH(2)O 1-4 (amino acid (aa): glycine (gly), 1; DL: -alanine (DL: -ala), 2; 2,2-dimethylglycine (C-dmg), 3; sarcosine (sar), 4), were synthesized and characterized by FTIR, elemental analysis, electrospray ionization-mass spectra (ESI-MS), UV-visible spectroscopy and molar conductivity measurement. The determined X-ray crystallographic structures of 2 and 3 show each to consist of distorted square pyramidal [Cu(phen)(aa)(H(2)O)](+) cation, a nitrate counter anion, and with or without lattice water, similar to previously reported structure of [Cu(phen)(gly)(H(2)O)]NO(3)·1½H(2)O. It is found that 1-4 exist as 1:1 electrolytes in aqueous solution, and the cationic copper(II) complexes are at least stable up to 24 h.

Ferrocenyl catechols: synthesis, oxidation chemistry and anti-proliferative effects on MDA-MB-231 breast cancer cells.

The synthesis and anti-tumoral properties of a series of compounds possessing a ferrocenyl group tethered to a catechol via a conjugated system is presented. On MDA-MB-231 breast cancer cell lines, the catechol compounds display a similar or greater anti-proliferative potency (IC(50) values ranging from 0.48-1.

Ultrafast vibrational relaxation dynamics of carbonyl stretching modes in Os3(CO)12.

The vibrational relaxation dynamics of the four infrared active carbonyl (CO) stretching normal modes of Os(3)(CO)(12) at 2068 cm(-1), 2034 cm(-1), 2014 cm(-1), and 2002 cm(-1) were measured using broad-band frequency resolved pump-probe spectroscopy. Transient absorption spectra of these modes were collected, and the fundamental, overtone, and combination bands were assigned. The frequency resolved pump-probe traces measured at the fundamental frequencies for the four stretching normal modes exhibited marked differences: the two axial modes at frequencies of 2068 cm(-1) and 2034 cm(-1) yielded similar bi-exponential decay traces, while the two equatorial modes at 2014 cm(-1) and 2002 cm(-1) showed a rising component, in addition to a bi-exponential decay.

Pro-oxidant properties of AZT and other thymidine analogues in macrophages: implication of the azido moiety in oxidative stress.

Zidovudine (azidothymidine, AZT) was the first drug approved for human immunodeficiency virus (HIV) treatment. Unfortunately, AZT is known to lead to severe side effects, many of which are generally thought to result from increased reactive oxygen species (ROS) production. In this work, the pro-oxidative properties of AZT and other thymidine analogues were investigated electrochemically at microelectrodes.

Osmium carbonyl clusters containing labile ligands hyperstabilize microtubules.

A study into the possible molecular targets of the osmium carbonyl cluster Os(3)(CO)(10)(NCCH(3))(2) (2) in the ER- breast carcinoma (MDA-MB-231) cell line was carried out. Infrared and (1)H NMR analyses of cells treated with 2 showed the formation of carboxylato- and thiolato-bridged clusters from the interaction with intracellular carboxylic acid and sulfhydryl residues. The cytotoxicity of 2 was reduced in the presence of fetal bovine serum, and measurement with Ellman's reagent as well as fluorescence confocal microscopy with tetramethylrhodamine-5-maleimide staining all demonstrated binding to intracellular sulfhydryl groups leading up to cell disruption.

The deposition of osmium carbonyl clusters onto inorganic oxide surfaces: a ToF-SIMS and IR spectroscopic study of the surface species.

The interaction between the osmium clusters [Os3(CO)12], [Os3(CO)10(mu-H)2], [Os3(CO)10(mu-H)(mu-OH)], and a series containing a free functional group, viz., [Os3(CO)10(mu-H)(mu-S--EH)] (where -- =alkylwedge chain or an aromatic ring, E=COO, S or O), with SiO2, ZnO and In2O3, was examined by ToF-SIMS and IR spectroscopy. While the interaction with the silica surface is mostly via an O atom or the functional group, the interaction with the ZnO and In2O3 surfaces is more complex.