Organometallic indolo[3,2-c]quinolines versus indolo[3,2-d]benzazepines: synthesis, structural and spectroscopic characterization, and biological efficacy

The synthesis of ruthenium(II) and osmium(II) arene complexes with the closely related indolo[3,2-c]quinolines N-(11H-indolo[3,2-c]quinolin-6-yl)-ethane-1,2-diamine (L1) and N′-(11H-indolo[3,2-c]quinolin-6-yl)-N,N-dimethylethane-1,2-diamine (L2) and indolo[3,2-d]benzazepines N-(7,12-dihydroindolo-[3,2-d][1]benzazepin-6-yl)-ethane-1,2-diamine (L3) and N′-(7,12-dihydroindolo-[3,2-d][1]benzazepin-6-yl)-N,N-dimethylethane-1,2-diamine (L4) of the general formulas [(η6-p-cymene)MII(L1)Cl]Cl, where M is Ru (4) and Os (6), [(η6-p-cymene)MII(L2)Cl]Cl, where M is Ru (5) and Os (7), [(η6-p-cymene)MII(L3)Cl]Cl, where M is Ru (8) and Os (10), and [(η6-p-cymene)MII(L4)Cl]Cl, where M is Ru (9) and Os (11), is reported. The compounds have been comprehensively characterized by elemental analysis, electrospray ionization mass spectrometry, spectroscopy (IR, UV–vis, and NMR), and X-ray crystallography (L1·HCl, 4·H2O, 5, and 9·2.5H2O). Structure–activity relationships with regard to cytotoxicity and cell cycle effects in human cancer cells as well as cyclin-dependent kinase (cdk) inhibition and DNA intercalation in cell-free settings have been established. The metal-free indolo[3,2-c]quinolines inhibit cancer cell growth in vitro, with IC50 values in the high nanomolar range, whereas those of the related indolo[3,2-d]benzazepines are in the low micromolar range. In cell-free experiments, these classes of compounds inhibit the activity of cdk2/cyclin E, but the much higher cytotoxicity and stronger cell cycle effects of indoloquinolines L1 and 7 are not paralleled by a substantially higher kinase inhibition compared with indolobenzazepines L4 and 11, arguing for additional targets and molecular effects, such as intercalation into DNA

Analysis of coordination and organometallic compounds using photoionisation mass spectrometric techniques

A range of coordination and organometallic compounds have been analysed by quadrupole ion-trap mass spectrometry using various photoionisation methods. Atmospheric-pressure photo ionisation (APPI), which combines atmospheric-pressure chemical ionisation (APCT) with a photolysis lamp, was compared with the new technique photo-assisted electrospray ionisation (PAESI). Additionally, the atmospheric pressure matrix-assisted laser desorption ionisation (AP-MALDI) was also evaluated and compared to MALDI quadrupole ion-trap time-of-flight (MALDI-QIT-TOF) mass spectrometry. (C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Development of organometallic (organo-transition metal) pharmaceuticals

This paper is aimed at introducing the organometallic chemist to the fascinating area of organometallic pharmaceuticals. It commences by identifying the properties of organometallic (transition metal) compounds that lend themselves to medical applications. Next, the specialized techniques and methods that are used to assess the medicinal properties of compounds are summarized, and although these techniques are not restricted to organometallic compounds, all examples are concerned with organometallic compounds. The design and evaluation of organometallic compounds for medicinal applications are described in context with the diseases they have been evaluated against, and areas are identified that may have most potential for organometallic pharmaceuticals. Some new results, including the first example of an organo-osmium compound that might exhibit effective anticancer properties, are also described. Copyright (C) 2004 John Wiley Sons, Ltd

ENCEPHALITE LIMBIQUE AUTO-IMMUNE : A PROPOS D’UN CAS AUTOIMMUNE LIMBIC ENCEPHALITIS: A CASE STUDY

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Osmium arenes : a new class of potential anti-cancer agents

Our studies of half-sandwich osmium(II) arene complexes of the type [(eta(6)-arene)Os(XY)Z] show that hydrolysis of the Os-Z (Z = Cl) bond and degree of formation of biologically inactive hydroxo-bridged dimers can be controlled by the choice of the chelated ligand XY. The chemistry and cancer-cell cytotoxicity of complexes containing N,N-, N,O-, or O,O-chelating ligands are compared and contrasted. The wide kinetic timescales of the reactions of these osmium complexes are notable and promising for the design of novel anti-cancer agents