A divalent heteroleptic lanthanoid fluoride complex stabilised by the tetraphenylcyclopentadienyl ligand, arising from C-F activation of pentafluorobenzene.

The divalent heteroleptic lanthanoid fluoride complex, [Yb(C5Ph4H)(µ-F)(thf)2]2, as well as [Yb(C5Ph4H)2(thf)] and [Yb(C5Ph4H)(C6F5)(thf)2] were obtained from reactions of ytterbium metal with Hg(C6F5)2 and tetraphenylcyclopentadiene under different conditions, and C-F activation of C6F5H by Yb metal was observed.

The Pathfinder image-guided surgical robot.

This paper first describes the workflow of the Pathfinder image-guided surgical robot that has been designed to replace the stereotactic frame in neurosurgery, and then details the calibration stages employed in order to achieve submillimetre positioning accuracy of a tool tip. The process uses non-linear parameter identification techniques in conjunction with some procedures for camera calibration, which exploit the fact that the camera is mounted to a calibrated robot arm that executes precise motions.

Engineering of efficient panchromatic sensitizers for nanocrystalline TiO(2)-based solar cells.

A new series of panchromatic ruthenium(II) sensitizers derived from carboxylated terpyridyl complexes of tris-thiocyanato Ru(II) have been developed. Black dye containing different degrees of protonation [(C(2)H(5))(3)NH][Ru(H(3)tcterpy)(NCS)(3)] 1, [(C(4)H(9))(4)N](2)[Ru(H(2)tcterpy)(NCS)(3)] 2, [(C(4)H(9))(4)N](3)[Ru(Htcterpy)(NCS)(3)] 3, and [(C(4)H(9))(4)N](4)[Ru(tcterpy)(NCS)(3)] 4 (tcterpy = 4,4',4' '-tricarboxy-2,2':6',2' '-terpyridine) have been synthesized and fully characterized by UV-vis, emission, IR, Raman, NMR, cyclic voltammetry, and X-ray diffraction studies. The crystal structure of complex 2 confirms the presence of a Ru(II)N6 central core derived from the terpyridine ligand and three N-bonded thiocyanates. Intermolecular H-bonding between carboxylates on neighboring terpyridines gives rise to 2-D H-bonded arrays. The absorption and emission maxima of the black dye show a bathochromic shift with decreasing pH and exhibit pH-dependent excited-state lifetimes. The red-shift of the emission maxima is due to better pi-acceptor properties of the acid form that lowers the energy of the CT excited state. The low-energy metal-to-ligand charge-transfer absorption band showed marked solvatochromism due to the presence of thiocyanate ligands. The Ru(II)/(III) oxidation potential of the black dye and the ligand-based reduction potential shifted cathodically with decreasing number of protons and showed more reversible character. The adsorption of complex 3 from methoxyacetonitrile solution onto transparent TiO(2) films was interpreted by a Langmuir isotherm yielding an adsorption equilibrium constant, K(ads), of (1.0 +/- 0.3) x 10(5) M(-1). The amount of dye adsorbed at monolayer saturation was (n(alpha) = 6.9 +/- 0.3) x 10(-)(8) mol/mg of TiO(2), which is around 30% less than that of the cis-di(thiocyanato)bis(2,2'-bipyridyl-4,4'-dicarboxylate)ruthenium(II) complex. The black dye, when anchored to nanocrystalline TiO(2) films achieves very efficient sensitization over the whole visible range extending into the near-IR region up to 920 nm, yielding over 80% incident photon-to-current efficiencies (IPCE). Solar cells containing the black dye were subjected to analysis by a photovoltaic calibration laboratory (NREL, U.S.A.) to determine their solar-to-electric conversion efficiency under standard AM 1.5 sunlight. A short circuit photocurrent density obtained was 20.5 mA/cm(2), and the open circuit voltage was 0.72 V corresponding to an overall conversion efficiency of 10.4%.

Diverse heteroleptic ytterbium(III) thiocyanate complexes by oxidation from bis(thiocyanato)ytterbium(II).

The new ytterbium(II) thiocyanate complex [Yb(NCS)2(thf)2] (1), synthesised by redox transmetallation between [Hg(SCN)2] and ytterbium metal in THF at room temperature, gave monomeric, eight coordinate [Yb-(NCS)2(dme)3] (2, dme = 1,2-dimethoxyethane) on crystallisation from DME, and is a powerful, synthetically useful reductant. Thus, oxidation of 1 with Hg(SCN)2, Hg(C6F5)2/HOdpp (HOdpp = 2,6-diphenylphenol), TlCp (Cp = C5H5 or CH3C5H4), Tl(Ph2pz) (Ph2pz = 3,5-diphenylpyrazolate) and CCl3CCl3 in THF yielded the ytterbium(II) complexes [Yb(NCS)3(thf)4] (3), [Yb-(NCS)2(Odpp)(thf)3](4), [Yb(NCS)2Cp-(thf)3] (Cp = C5H5 (5), CH3C5H4 (6)), [Yb(NCS)2(Ph2pz)(thf)4] (7) and [Yb(NCS)2Cl(thf)4] (8). In the solid state, complexes 4, 6 and 7 were shown by X-ray crystallography to be six, eight and eight coordinate monomers, respectively. Exclusively terminal, N-bound transoid thiocyanate bonding is observed with eta1-Odpp (4), eta5/-C5H4Me (6) and eta2-Ph2Pz (7) ligands attached approximately perpendicular to the N...N vector. The chloride complex 8 is not a molecular species, but consists of discrete, seven coordinate [YbCl2(thf)5] cations and [Yb(NCS)4(thf)3] anions. By contrast, oxidation of 1 with TlO2CPh gave a mixture of [[Yb(NCS)-(O2CPh)2(thf)2]2] (9) and 3 through rearrangement of an initially formed [Yb(NCS)2(O2CPh)] species. The X-ray structure of 9 indicates a dimeric complex with a (Yb(mu-O2CPh)4Yb] core that contains both bridging bidentate and bridging tridentate benzoate groups, and with a terminal N-bound thiocyanate and two THF ligands on each ytterbium. Reduction of Ph2CO with 1 in THF yielded the dinuclear complex [[Yb(NCS)2(thf)3]2(mu-OC(Ph)2C(Ph)2O)] (10), in which two octahedral Yb centres are bridged by a 1,1,2,2-tetraphenylethane-1,2-diolate ligand, derived from reductive coupling of the benzophenone reagent.

Simple syntheses, structural diversity, and Tishchenko reaction catalysis of neutral homoleptic rare earth(II or III) 3,5-di-tert-butylpyrazolates--the structures of.

The homoleptic rare-earth pyrazolate complexes [Sc(tBu2pz)3], [Ln2(tBu2pz)6] (Ln = La, Nd, Sm, Lu), [Eu4(tBu2pz)8] and the mixed oxidation state species [Yb2(tBu2pz)5] (tBu2pz = 3,5-di-tert-butylpyrazolate) have been prepared by a simple reaction between the corresponding rare-earth metal and 3,5-di-tert-butylpyrazole, in the presence of mercury, at elevated temperatures. In addition, [Yb2(tBu2pz)6] was prepared by redox transmetallation/ligand exchange between ytterbium, diphenylmercury(II) and tBu2pzH in toluene, whilst the same reactants in toluene under different conditions or in diethyl ether gave [Yb2(tBu2pz)5]. The complexes of the trivalent lanthanoids display dimeric structures [Ln2(tBu2pz)6] (Ln = La, Nd, Yb, Lu) with chelating eta2-terminal and eta2:eta2-bridging pyrazolate coordination. The considerably smaller Sc3+ ion forms monomeric [Sc(tBu2pz)3] of putative D3h molecular symmetry, with pyrazolate ligands solely eta2-bonded. [Eu4(tBu2pz)8] is a structurally remarkable tetranuclear EuII complex with two types of europium centres in a linear array. The outer two are bonded to one terminal and two bridging pyrazolates, and the inner two are coordinated by four bridging ligands. Unprecedented mu-eta5:eta2 pyrazolate ligation is observed, with each outer Eu2+ sandwiched between two eta5-bonded pyrazolate groups, which are also eta2-linked to an inner Eu2+. The two inner Eu2+ ions are linked together by two equally occupied components of each of two symmetry related, disordered pyrazolate groups with one component eta4:eta2 bridging and one eta3:eta2 bridging. [La2(tBu2pz)6] has also been shown to be a Tishchenko reaction catalyst with several organic substrates.

Nuclear and mitochondrial distribution of organoamidoplatinum(II) lesions in cisplatin-sensitive and -resistant adenocarcinoma cells.

The DNA binding pattern of the organoamidoplatinum(II) compound 1a is of considerable interest because of its known activity against cisplatin-resistant cells. The activity of 1a appears to be due at least in part to a greater cellular uptake than cisplatin into cisplatin-resistant cells, but little is known of the DNA reactions of the organoamidoplatinum(II) compounds. In this study the level of DNA cross-linking and total DNA lesions formed by 1 a were measured by gene-specific Southern hybridization cross-linking assays and by quantitative PCR in cisplatin-sensitive (2008) and in cisplatin-resistant 2008/R human adenocarcinoma cell lines. The surprising result was that the major difference between cisplatin and 1a was that the number of interstrand cross-links induced by 1a were approximately 5-fold greater than that induced by cisplatin in the nuclear (but not mitochondrial) DNA of resistant cells, even though the total number of lesions were essentially the same in both sensitive and resistant cells. This result suggests that the extent of interstrand cross-linking is a critical determinant of the cellular response to 1a and that the enhanced uptake of 1a into resistant cells results in this elevated level of cross-linking, leading to good activity of 1a against cisplatin-resistant cells. It remains unclear as to why 1a exhibits such selective damage to nuclear DNA, and insight into the molecular aspects of this selectivity will provide new opportunities for the further development of new platinum-based agents with activity against cisplatin-resistant cells.

Activity and DNA binding of new organoamidoplatinum (II) complexes.

Two series of organoamidoplatinum (II) complexes were synthesized [Class 1, Pt(NRCH2)2L2 and Class 2, Pt(NRCH2CH2NR2')L(X)] and their antitumour activity examined by a range of in vitro, cellular and animal studies. All Class 1 compounds exhibited activity comparable to cisplatin in mouse leukemia L1210 cells, but were at least 8-fold more active against the cisplatin-resistant L1210/R line. The lead compound 1a (R=p-HC6F4) caused nearly complete tumour regression in the ADJ/PC6 mouse tumour model. Compound 1a exhibited similar DNA reactivity to cisplatin, resulting in virtually identical DNA sequence specificity as cisplatin, and had similar time and concentration dependency of interstrand crosslinks. Compared with cisplatin, la showed 3-fold greater cellular uptake into human ovarian carcinoma 2008 cells, and this was dramatically enhanced to 17-fold in the cisplatin-resistant 2008/R line. The activity of 1a, therefore, appears to be due at least in part to a greater cellular uptake into tumour cells, particularly cisplatin-resistant cells, and once in the cell it reacts with DNA in a similar manner to that of cisplatin. The enhanced uptake and enhanced cytotoxicity of Class 1 compounds, and 1a in particular, may be due to a greater hydrophobicity compared with cisplatin. The activity of the Class 2 compounds, especially in the cisplatin-resistant cell lines, is unusual because they have trans amine ligands, and further study of both classes of compounds is warranted.

Modifying the properties of platinum (IV) complexes in order to increase biological effectiveness.

The preparation of a series of novel Pt(IV) complexes containing the anionic polyfluoroaryl ligands, 2,3,5,6-tetrafluorophenyl (p-HC6F4), 2,3,5,6-tetrafluoro-4-methoxyphenyl (p-MeOC6F4) and pentafluorophenyl (C6F5) are described. The crystal structure of a representative complex, [Pt(p-MeOC6F4)2(O2CEt)2(en)] (en = ethane-1,2-diamine) was determined and confirms the trans arrangement of the carboxylato ligands. Reduction potentials of the series of complexes reveal that replacement of equatorial chloro ligands by polyfluoroaryl ligands makes reduction substantially more difficult. They also confirm previously reported trends in that complexes having axial carboxylato ligands are more readily reduced than those having axial hydroxo ligands. Reduction potentials and in vitro activities showed no obvious correlations. Moderate to high activity was observed for many complexes in the series, including some of those that were very difficult to reduce.

Preparation and Anti-Tumour Activity of Some Arylbismuth(III) Oxine Complexes.

New arylbismuth(lll) oxinates, PhBi(MeOx)(2), (p-MeC(6)H(4))Bi(Ox)(2), (p-MeC(6)H(4))Bi(MeOx)(2), (p-ClC(6)H(4))Bi(Ox)(2), and (p-ClC(6)H(4))Bi(MeOx)(2) (Ox(-) = quinolin-8-olate and MeOx(-)=2-methylquinolin-8-olate) have been prepared by reaction of the appropriate diarylbismuth chlorides with Na(Ox) or Na(MeOx) in the presence of 15-crown-5. An X-ray crystallographic study has shown PhBi(MeOx)(2) to be a five coordinate monomer with distorted square pyramidal stereochemistry. Chelating MeOx ligands have a cisoid arrangement in the square plane and the phenyl group is apical. The lattice is stabilised by significant pi-pi interactions between centrosymmetric molecules. A range of these complexes has been shown to have high in vitro biological activity (comparable with or better than cisplatin) against L1210 leukaemia, the corresponding cisplatin resistant line, and a human ovarian cell line, SKOV-3. However, initial in vivo testing against a solid mouse plasmacytoma (PC6) and P388 leukaemia has not revealed significant activity.

cis-bis(pyridine)platinum(II) organoamides with unexpected growth inhibition properties and antitumor activity.

The platinum(II) organoamides [Pt(NRCH2)2L2] (L = pyridine (py), R = p-HC6F4, C6F5,p-IC6F4,p-CIC6F4,p-C6F5C6F4; L = 4-methylpyridine, R = p-HC6F4) and [Pt(NRCH2CH2NR')(py)2] (R = p-HC6F4, R' = C6F5, p-BrC6F4, or p-MeC6F4) inhibit the growth of murine L1210 leukemia cells in culture with ID50 values for continuous exposure in the range 0.6-2.7 microM. Representative complexes are also active against L1210 cells in 2-h pulse exposures, as well as against the cisplatin-resistant variant L1210/DDP and human colonic carcinoma cell lines HT 29 and BE. Three complexes [Pt(NRCH2)2L2] (R = p-HC6F4, C6F5, or p-IC6F4) have good activity (T/C greater than or equal to 180%) against P388 leukemia in mice, and all other compounds tested are active except when R = p-C6F5C6F4, L = py. Although the molecular basis of the biological activity of these complexes is not known, the observation of good activity for amineplatinum(II) compounds with no hydrogen substituents on the nitrogen donor atoms introduces a new factor in the anticancer behavior of platinum(II) complexes.

Octanol/water partition coefficients as a model system for assessing antidotes for methylmercury(II) poisoning, and for studying mercurials with medicinal applications.

1-Octanol/water partition coefficients, [HgII]octanol/[HgII]water, provide a simple but limited model system for aspects of the biological behavior of methylmercury(II) and commonly used organomercury(II) medicinal compounds. In an octanol/water system some widely studied antidotes for mercury poisoning at least partly displace the biological thiols L-cysteine and glutathione from binding to MeHgII at pH 6.9. Addition of the antidote meso-dimercaptosuccinic acid to MeHgII in the presence of glutathione results in formation of metallic mercury. For RHgII derivatives of L-cysteine and glutathione, octanol/water partition coefficients follow the order Ph greater than Et greater than Me. An exceptionally high value for diphenylmercury, compared with PhHgII derivatives of L-cysteine and glutathione, is consistent with reported results of the distribution of mercury compounds in rats. Ethylmercury(II) is partly displaced from thimerosal by L-cysteine and glutathione in the octanol/water system, indicating that the active form of thimerosal in vivo may involve binding of EtHgII to biological ligands.

Chelation therapy for methylmercury(II) poisoning. Synthesis and determination of solubility properties of MeHg(II) complexes of thiol and dithiol antidotes.

Methylmercury(II) complexes of the most widely studied antidotes for mercury poisoning have been prepared, and both the water solubility and 1-octanol/water partition coefficients determined for these complexes and the L-cysteine complex. New complexes of N-acetyl-D,L-penicillamine, 2-mercaptosuccinic acid, meso-dimercaptosuccinic acid, and Unithiol have been synthesized and characterized, and are found to have the formulations MeHgSCMe2CH(NHCOMe)CO2H, MeHgSCH(CO2H)CH2CO2H, MeHgSCH(CO2H)CH(CO2H)SHgMe, and Na[MeHgSCH2CH-(SHgMe)CH2SO3], respectively. Trends in octanol/water partition coefficients are consistent with reported studies of the effectiveness of antidotes for MeHg(II) poisoning and redistribution of MeHg(II) on administration of antidotes, particularly for British anti-Lewisite, Unithiol, and meso-dimercaptosuccinic acid.

Problem drinkers and their problems.

From general practice records of 9,763 patients, 106 problem drinkers were compared with a control group. The drinkers had a substantially higher number of problems and they consulted their doctor and attended casualty departments frequently. Social and marital problems were especially prevalent in the families of problem drinkers.

Campylobacter: common cause of enteritis in an infectious diseases hospital.

Eleven patients were referred to the infectious diseases wards of the Prince Henry Hospital, Sydney, between August and December, 1979, with acute infectious diarrhoea acquired within Australia. Nine of the 11 had infection with Campylobacter species as the sole pathogens. In contrast, a variety of pathogens was isolated from the stools of 13 patients referred to the hospital with enteritis acquired during overseas travel, including three Shigella species, but only one Campylobacter species. The patients with campylobacter enteritis suffered fever, abdominal discomfort and diarrhoea, often with some blood. Complications of campylobacter enteritis included colitis, severe abdominal pain, renal failure, severe muscle cramps, headache with meningism, myalgias and arthralgias. Campylobacter enteritis resolved with cessation of solid food intake, together with intravenous or oral fluid therapy. Some patients were treated with erythromycin, with prompt improvement, though a role for antibiotic therapy has not yet been established.