Weng Kee Leong

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.

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 0.48-1.21 μM) than their corresponding phenolic analogues (0.57-12.7 μM), with the highest activity found for species incorporating the [3]ferrocenophane motif. On the electrochemical timescale, phenolic compounds appear to oxidize to the quinone methide, while catechol moieties form the o-quinone by a similar mechanism. Chemical oxidation of selected compounds with Ag(2)O confirms this interpretation and demonstrates the probable involvement of such oxidative metabolites in the in vitro activity of these species.

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. Analysis of restriction enzyme inhibition by these four complexes revealed modulation of DNA binding selectivity by the type of ligand, ligand modification and chirality. Their interaction with bovine serum albumin was investigated by FL and electronic spectroscopy. With the aid of the crystal structure of BSA, spectroscopic evidence suggested their binding at the cavity containing Trp134 with numerous Tyr residues in subdomain IA. The products were more antiproliferative than cisplatin against cancer cell lines HK-1, MCF-7, HCT116, HSC-2 and C666-1 except HL-60, and were selective towards nasopharyngeal cancer HK-1 cells over normal NP69 cells of the same organ type.

Structural characterisation of the elusive isomer of Os3(CO)10(PPh3)2

Abstract The X-ray crystal structure of the elusive isomer of Os3(CO)10(PPh3)2 in which the two phosphine ligands are cis and trans with respect to the phosphine-substituted Os–Os edge has been determined; the first direct confirmation for the existence of this isomer in Os3(CO)10(PR3)2 clusters. In contrast to the trans,trans isomer, the cis,trans isomer shows little twisting of the Os(CO)3(PPh3) groupings with respect to the Os(CO)4 unit.

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 Ellmans reagent as well as fluorescence confocal microscopy with tetramethylrhodamine-5-maleimide staining all demonstrated binding to intracellular sulfhydryl groups leading up to cell disruption. Tubulin-FITC antibody staining of treated cells showed disruption of the microtubules, and a tubulin polmerization assay showed that 2 induced hyperstabilization of the microtubules.

Osmium carbonyl clusters: a new class of apoptosis inducing agents.

Osmium carbonyl clusters, especially the cluster [Os3(CO)10(NCCH3)2], were found to be active against four cancer cell lines, namely, ER+ breast carcinoma (MCF‐7), ER− breast carcinoma (MDA‐MB‐231), metastatic colorectal adenocarcinoma (SW620), and hepatocarcinoma (Hep G2). The mode of action was studied in MCF‐7 and MDA‐MB‐231 cell lines by a number of morphological and apoptosis assays, all of which pointed to the induction of apoptosis.

Steric and Electronic Influences in Os~3(CO)~1~1(PR~3) Structures

The structures of Os3(CO)11(PR3) with R=F, OPh, Et, p-C6H4Me, o-C6H4Me, p-C6H4(CF3) and C6H11, and with PR3=P(OCH2)3CMe have been determined. The Os–Os bond lengths in these compounds are compared to the Os–Os lengths for the other structures of Os3(CO)11(PR3) clusters reported in the literature. In most cases, the Os–Os bond length remote from the P ligand [range, 2.8666(4)–2.9044(4) Å] and that in the pseudo-trans position [range, 2.8712(5)–2.900(1) Å] show little variation as the steric and electronic properties of the P ligand are varied. The Os–Os length cis to PR3 shows more variation [range, 2.879(1)–2.9429(4) Å] and is sensitive to both the size and the σ-donor/π-acceptor properties of the PR3 ligand: larger or better donor PR3 ligands cause an increase in the Os–Os bond length. The Os–P distances [range, 2.15(2)–2.478(1) Å] show a similar dependence on the steric and electronic properties of the PR3 ligand.

The heteronuclear cluster RuOs3(μ-H)2(CO)13 — a high yield synthesis, isomerism and a triphenylphosphine derivative

Abstract A high-yielding alternative synthesis of the heteronuclear cluster RuOs 3 (μ-H) 2 (CO) 13 has been developed. It is also demonstrated that the cluster exists as at least three isomers, which rapidly interconvert in solution. A triphenylphosphine derivative, RuOs 3 (μ-H) 2 (CO) 12 (PPh 3 ), has also been prepared; this exists as two isomers, both of which have been characterised by single-crystal X-ray crystallographic studies.

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. Macrophages pre‐incubated with AZT were found to release significant amounts of reactive species, including H2O2, ONOO−, NO. and NO2−. Interestingly, the total amounts of released species were the greatest when cells were incubated with azido‐containing analogues. The pro‐oxidative effect of these compounds decreased significantly when the free azide terminal group was modified by reaction with a triosmium cluster. As expected, thymidine incubation did not lead to any increase in overall ROS levels. This work implicates the azido moiety in AZT‐induced oxidative stress.

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−nLn, 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. In particular, the maltolato cluster exhibits strong antiproliferative activity, with an IC50 value of 3 μM after only 24 h incubation. Additionally, biochemical assays conducted with the cationic cluster show that it induces apoptosis, although a biological target has not yet been identified. Further research to establish the molecular targets of these compounds and to develop improved organometallic clusters as potential breast cancer therapeutics is underway.