Multipurpose Iron-Chelating Ligands Inspired by Bioavailable Molecules.

Because of their capacity to bind metals, metal chelators are primarily employed for therapeutic purposes, but they can also find applications as colorimetric reagents and cleaning solutions as well as in soil remediation, electroplating, waste treatment, and so on. For instance, iron-chelation therapy, which is used to treat iron-overload disorders, involves removing excess iron from the blood through the use of particular molecules, like deferoxamine, that have the ability to chelate the metal. The creation of bioinspired and biodegradable chelating agents is a crucial objective that draws inspiration from natural products. In this context, starting from bioavailable molecules such as maltol and pyrogallol, new molecules have been synthetized and characterized by potentiometry, infrared spectroscopy and cyclic voltammetry. Finally, the ability of these to bind iron has been investigated, and the stability constants of ferric complexes are measured using spectrophotometry. These compounds offer intriguing scaffolds for an innovative class of versatile, multipurpose chelating agents.

Inverted Ligand Field in a Pentanuclear Bow Tie Au/Fe Carbonyl Cluster.

Gold chemistry has experienced in the last decades exponential attention for a wide spectrum of chemical applications, but the +3 oxidation state, traditionally assigned to gold, remains somewhat questionable. Herein, we present a detailed analysis of the electronic structure of the pentanuclear bow tie Au/Fe carbonyl cluster [Au{η2-Fe2(CO)8}2]- together with its two one-electron reversible reductions. A new interpretation of the bonding pattern is provided with the help of inverted ligand field theory. The classical view of a central gold(III) interacting with two [Fe2(CO)8]2- units is replaced by Au(I), with a d10 gold configuration, with two interacting [Fe2(CO)8]- fragments. A d10 configuration for the gold center in the compound [Au{η2-Fe2(CO)8}2]- is confirmed by the LUMO orbital composition, which is mainly localized on the iron carbonyl fragments rather than on a d gold orbital, as expected for a d8 configuration. Upon one-electron stepwise reduction, the spectroelectrochemical measurements show a progressive red shift in the carbonyl stretching, in agreement with the increased population of the LUMO centered on the iron units. Such a trend is also confirmed by the X-ray structure of the direduced compound [Au{η1-Fe2(CO)8}{η2-Fe2(CO)6(µ-CO)2}]3-, featuring the cleavage of one Au-Fe bond.

Hibiscus Flower and Olive Leaf Extracts Activate Apoptosis in SH-SY5Y Cells.

Compounds of natural origin may constitute an interesting tool for the treatment of neuroblastoma, the most prevalent extracranial solid tumor in children. PRES is a commercially available food supplement, composed of a 13:2 (w/w) extracts mix of Olea europaea L. leaves (OE) and Hibiscus sabdariffa L. flowers (HS). Its potential towards neuroblastoma is still unexplored and was thus investigated in human neuroblastoma SH-SY5Y cells. PRES decreased the viability of cells in a concentration-dependent fashion (24 h IC50 247.2 ± 31.8 µg/mL). Cytotoxicity was accompanied by an increase in early and late apoptotic cells (AV-PI assay) and sub G0/G1 cells (cell cycle analysis), ROS formation, reduction in mitochondrial membrane potential, and caspases activities. The ROS scavenger N-acetyl-L-cysteine reverted the cytotoxic effects of PRES, suggesting a key role played by ROS in PRES-mediated SH-SY5Y cell death. Finally, the effects of OE and HS extracts were singularly tested and compared to those of the corresponding mixture. OE- or HS-mediated cytotoxicity was always significantly lower than that caused by PRES, suggesting a synergic effect. In conclusion, the present findings highlight the potential of PRES for the treatment of neuroblastoma and offers the basis for a further characterization of the mechanisms underlying its effects.

Polyphenols: From Theory to Practice.

BACKGROUND: The importance of polyphenols in human health is well known; these compounds are common in foods, such as fruits, vegetables, spices, extra virgin olive oil and wine. On the other hand, the different factors that modulate the biological activity of these compounds are less well known. Conceptualization of the work: In this review we took into account about 200 relevant and recent papers on the following topics: "polyphenols bioavailability", "polyphenols matrix effect", "food matrix effect", "polyphenols-cytochromes interaction", after having reviewed and updated information on chemical classification and main biological properties of polyphenols, such as the antioxidant, anti-radical and anti-inflammatory activity, together with the tricky link between in vitro tests and clinical trials. KEY FINDINGS: the issue of polyphenols bioavailability and matrix effect should be better taken into account when health claims are referred to polyphenols, thus considering the matrix effect, enzymatic interactions, reactions with other foods or genetic or gender characteristics that could interfere. We also discovered that in vitro studies often underrate the role of phytocomplexes and thus we provided practical hints to describe a clearer way to approach an investigation on polyphenols for a more resounding transfer to their use in medicine.

Antioxidant Effect of the Castanea sativa Mill. Leaf Extract on Oxidative Stress Induced upon Human Spermatozoa.

This study was aimed at evaluating in vitro the effects of a 75% v/v ethanolic extract of leaves of Castanea sativa Mill. (var. Bastarda Rossa, Mount Amiata, Tuscany, Italy) on ejaculated human sperm. Total polyphenols and total flavonoids contained in the extract were determined by a colorimetric assay and HPLC-DAD. The DPPH test and electrochemistry were utilized to study the antioxidant activity of the extract. Swim-up-selected sperm from 8 healthy men were treated with the C. sativa leaf extract at different dilutions (1 : 100, 1 : 200, and 1 : 500), and sperm motility was assessed following the WHO guidelines. Swim-up-selected spermatozoa were incubated with 100 µM H2O2 to induce lipid peroxidation (LPO) and with H2O2 and the leaf extract (1 : 100, 1 : 200, and 1 : 500) to test the antioxidant activity of the extract. The levels of LPO were determined by measuring malondialdehyde (MDA) concentrations. The treated samples were also analyzed by transmission electron microscopy (TEM) for ultrastructural evaluation. The chemical analysis showed that one-third ca. of the polyphenols in the C. sativa extract were made up of flavonoids, with hyperoside present in high concentration. A good antioxidant activity was demonstrated by both the DPPH test and electrochemical analysis. The C. sativa leaf extract did not decrease sperm motility at all tested dilutions. Treatment with H2O2 alone caused a significant increment in MDA levels (P = 0.006993), while the treatment with H2O2 plus C. sativa extract diluted to 1 : 100 and 1 : 200 significantly reduced MDA levels (P = 0.01476 and P = 0.01571, respectively), with respect to H2O2 alone. TEM analysis confirmed the protective effect of the extract on damage induced by LPO, in particular that occurring at the plasma membrane level. The C. sativa leaf extract could be used in human and farm animal protocols for gamete handling, such as techniques of assisted reproduction and cryopreservation of semen, all conditions in which oxidative stress is exacerbated.

Synthesis of 13-vertex dimetallacarboranes by electrophilic insertion into 12-vertex ruthenacarboranes.

The electrophilic insertion of organometallic species into metallacarboranes was studied in detail for the model compound - the 12-vertex closo-ruthenacarborane anion [Cp*Ru(C2B9H11)]- (1). Reactions of the anion 1 with the 12-electron cationic species [M(ring)]+ (M(ring) = RuCp, RuCp* and Co(C4Me4)) gave the 13-vertex closo-dimetallacarboranes Cp*Ru(C2B9H11)M(ring). Similar reactions of the neutral ruthenacarborane Cp*Ru(Me2S-C2B9H10) produce the cationic dimetallacarboranes [Cp*Ru(Me2S-C2B9H10)M(ring)]+. The symmetrical 13-vertex diruthenacarboranes (C5R5)Ru(R2C2B9H9)Ru(C5R5) can be prepared by the direct reactions of Tl2[7,8-R2-7,8-C2B9H9] (R = H and Me) with two equivalents of [CpRu(MeCN)3]+ or [Cp*RuCl]4. The insertions of the 14-electron cationic species [M(ring)]+ (M(ring) = NiCp, NiCp* and Co(C6Me6)) into 1 gave the 13-vertex dimetallacarboranes Cp*Ru(C2B9H11)M(ring), which have a distorted framework with one open face. The structures of Cp*Ru(C2B9H11)Co(C4Me4) and Cp*Ru(C2B9H11)NiCp were established by X-ray diffraction. Some of the 13-vertex dimetallacarboranes have two electrons less than required by Wade's rules. This violation is explained by the absence of the appropriate pathway for the distortion of the framework.

The First Triple-Decker Complex with a Carbenium Center, [CpCo(µ-C3 B2 Me5 )RuC5 Me4 CH2 ]+ : Synthesis, Reactivity, X-Ray Structure, and Bonding.

The first derivative of the methylium cation with the triple-decker substituent, [CpCo(C3 B2 Me5 )RuC5 Me4 CH2 ]PF6 (2PF6 ), was synthesized from the reaction of the triple-decker complex CpCo(C3 B2 Me5 )RuCp* (1) with the salt of the trityl cation [CPh3 ]+ . The X-ray crystal structure of 2PF6 reveals that the methylium carbon is bound to the ruthenium with Ru-C bond length of 2.259 Šand corresponds to the description of its structure as η6 -fulvene-ruthenium. Reactions of 2PF6 with nucleophiles OH- , Ph3 P, Et3 N led to the corresponding derivatives of 1 in high yields. Aromatic amines PhNEt2 and 4-MeC6 H4 NH2 react with 2PF6 to give the electrophilic aromatic substitution products quantitatively. Chemical reduction of 2PF6 with Zn powder in tetrahydrofuran leads to the formation of the bis(triple-decker) derivative (CpCo(C3 B2 Me5 )RuC5 Me4 CH2 )2 (10) with a CH2 CH2 -bridge. The structures of complexes 4, 7-10 were determined by X-ray diffraction. Density functional calculations support the crystallographically determined geometry of 2 and allow rationalization of some characteristics of its structure, spectroscopy, and reactivity.

Dinuclear Pt(II)-bisphosphonate complexes: a scaffold for multinuclear or different oxidation state platinum drugs.

Geminal bisphosphonates (BPs), used in the clinic for the treatment of hypercalcaemia and skeletal metastases, have been also exploited for promoting the specific accumulation of platinum antitumor drugs in bone tissue. In this work, the platinum dinuclear complex [{Pt(en)}(2)(µ-AHBP-H(2))](+) (1) (the carbon atom bridging the two phosphorous atoms carrying a 2-ammonioethyl and a hydroxyl group, AHBP-H(2)) has been used as scaffold for the synthesis of a Pt(II) trinuclear complex, [{Pt(en)}(3)(µ-AHBP)](+) (2), and a Pt(IV) adamantane-shaped dinuclear complex featuring an oxo-bridge, [{Pt(IV)(en)Cl}(2)(µ-O)(µ-AHBP-H(2))](+) (3) (X-ray structure). Compound 2 undergoes a reversible, pH dependent, rearrangement with a neat switch point around pH = 5.4. Compound 3 undergoes a one-step electrochemical reduction at E(pc) = -0.84 V affording compound 1. Such a potential is far lower than that of glutathione (-0.24 V), nevertheless compound 3 can undergo chemical reduction to 1 by GSH, most probably through a different (inner-sphere) mechanism. In vitro cytotoxicity of the new compounds, tested against murine glioma (C6) and human cervix (HeLa) and hepatoma (HepG2) cell lines, has shown that, while the Pt(IV) dimer 3 is inactive up to a concentration of 50 µM, the two Pt(II) polynuclear compounds 1 and 2 have a cytotoxicity comparable to that of cisplatin with the trinuclear complex 2 generally more active than the dinuclear complex 1.

X-ray structure and density functional theory studies of an unexpected product: trans-bis{2-[(2-cyanoethyl)iminomethyl]phenolato}copper(II).

The title compound, [Cu(C(10)H(9)N(2)O)(2)] or [Cu(II)(CYMB)(2)], (I), was obtained in an attempt to reduce trans-bis(2-{[3,5-bis(trifluoromethyl)phenyl]iminomethyl}phenolato)copper(II), [Cu(TIMB)(2)], (II), with bis(pentamethylcyclopentadienyl)cobalt(II) [decamethylcobaltocene, Cp*(2)Co, (III)]. The molecular structure of (I) has the Cu(II) centre located on an inversion centre of the C2/c space group. A density functional theory (DFT) analysis at the B3LYP/Lanl2dz(CuF);6-31G**(CHNO) level performed in order to optimize the structures of the free ligands CYMB(-) and TIMB(-), and the metal complexes [Cu(I/II)(CYMB)(2)](-/0) and [Cu(I/II)(TIMB)(2)](-/0), reproduced well the X-ray diffraction structure and allowed us to infer the insertion of the cyanomethide anion on the 3,5-bis(trifluoromethyl)phenyl system from an evaluation of the Mulliken atomic charges and the electronic energies.

Chemical and biological profiles of novel copper(II) complexes containing S-donor ligands for the treatment of cancer.

In the last years, we have synthesized some new platinum(II), palladium(II), gold(I/III) complexes with dithiocarbamato derivatives as potential anticancer drugs, to obtain compounds with superior chemotherapeutic index in terms of increased bioavailability, higher cytotoxicity, and lower side effects than cisplatin. On the basis of the obtained encouraging results, we have been studying the interaction of CuCl2 with methyl-/ethyl-/tert-butylsarcosine-dithiocarbamato moieties in a 1:2 molar ratio; we also synthesized and studied the N,N-dimethyl- and pyrrolidine-dithiocarbamato copper complexes for comparison purposes. The reported compounds have been successfully isolated, purified, and fully characterized by means of several spectroscopic techniques. Moreover, the electrochemical properties of the designed compounds have been studied through cyclic voltammetry. In addition, the behavior in solution was followed by means of UV-vis technique to check the stability with time in physiological conditions. To evaluate their in vitro cytotoxic properties, preliminary biological assays (MTT test) have been carried out on a panel of human tumor cell lines. The results show that cytotoxicity levels of all of the tested complexes are comparable or even greater than that of the reference drug (cisplatin).

Structural characterization, solution studies, and DFT calculations on a series of binuclear gold(III) oxo complexes: relationships to biological properties.

A series of structurally related oxo-bridged binuclear gold(III) compounds, [Au2(mu-O)2(N;N)2](PF6)2, where N;N is 2,2'-bipyridine or a substituted 2,2'-bipyridine, have recently been shown to exhibit appreciable stability under physiological-like conditions and to manifest important antiproliferative effects toward selected human tumor cell lines (J. Med. Chem. 2006, 49, 5524). The crystal structures of four members of this series, namely, [Au2(mu-O)2(bipy)2](PF6)2, cis-[Au2(mu-O)2(6-Mebipy)2](PF6)2, trans-[Au2(mu-O)2(6-oXylbipy)2](PF6)2, and [Au2(mu-O)2(6,6'-Me2bipy)2](PF6)2, have been solved here and the respective structural parameters comparatively analyzed. Remarkably, all of the compounds contain a common structural motif consisting of a Au2O2 "diamond core" linked to two bipyridine ligands in a roughly planar arrangement. Interestingly, introduction of different kinds of alkyl or aryl substituents on the 6 (and 6') position(s) of the bipyridine ligand leads to small structural changes that nonetheless greatly affect the reactivity of the metal centers. The chemical behavior of these compounds in solution has been studied in detail, focusing in particular on the electrochemical properties. Some initial correlations among the structural parameters, the chemical behavior in solution, and the known cytotoxic effects of these compounds are proposed. Notably, we have found that the 6,6'-dimethyl-2,2'-bipyridine derivative, which showed the largest structural deviations with respect to the model compound [Au2(mu-O)2(bipy)2](PF6)2, also had the highest oxidizing power, the least thermal stability, and the greatest cytotoxic activity. The positive correlation that exists between the oxidizing power and the antiproliferative effects seems to be of particular interest. Moreover, the electronic structures of these compounds were extensively analyzed using DFT methods, and the effects of the various substituents on reactivity were predicted; overall, very good agreement between theoretical expectations and experimental data was achieved. In turn, theoretical predictions offer interesting hints for the design of new, more active binuclear gold(III) compounds.

Ru(III)-based compounds with sulfur donor ligands: synthesis, characterization, electrochemical behaviour and anticancer activity.

In recent years, Ru(iii) complexes have emerged as a new class of effective anticancer agents against tumors that proved to be resistant to all other chemotherapeutic drugs currently in clinical use. To extend our previous studies on metal complexes containing sulfur-donor ligands, we report here on the synthesis and characterization, by means of several spectroscopic and analytical techniques, some [Ru(RSDT)(3)] and [Ru(2)(RSDT)(5)]Cl complexes with dithiocarbamato ligands derived from methyl/ethyl/tert-butyl esters of sarcosine. Their electrochemical behaviour was also studied by cyclic voltammetry. All the complexes were tested for their cytotoxicity on a panel of human tumor cell lines showing highly significant antitumor activity. The chemical and biological properties of the newly synthesized complexes, were compared with those of [Ru(DMDT)(3)] and [Ru(2)(DMDT)(5)]Cl species (DMDT = N,N-dimethyldithiocarbamate) whose chemical (not biological) characterization has been already reported in literature.

Activity of rat cytosolic thioredoxin reductase is strongly decreased by trans-[bis(2-amino-5- methylthiazole)tetrachlororuthenate(III)]: first report of relevant thioredoxin reductase inhibition for a ruthenium compound.

A novel "Keppler type" ruthenium(III) compound trans-[bis(2-amino 5-methylthiazole)tetrachlororuthenate(III)] 1, of potential interest as an anticancer agent, was designed, synthesized, and characterized. Its interactions with various proteins were analyzed, including the selenoenzyme thioredoxin reductase, an emerging target for anticancer metallodrugs. The selective inhibition of the cytosolic form of this selenoenzyme was documented, this being the first report of significant thioredoxin reductase inhibition by a ruthenium compound.

New copper(II)/cyclic tetrapeptide system that easily oxidizes to copper(III) under atmospheric oxygen.

A 13-membered ring cyclic tetrapeptide was synthesized by the solid-phase peptide synthesis method, and its copper(II) coordination properties were analyzed by optical spectroscopy, mass spectrometry, and electrochemistry. All collected data strongly support the presence, at alkaline pH, of a stable peptide/copper(III) complex that is formed in solution by atmospheric dioxygen oxidation. On the basis of previous studies on cyclic peptide/copper systems, we suggest that the copper(III) ion is at the center of the ligand's cavity being coordinated to four deprotonated amide nitrogen atoms. This donor set would greatly lower the redox potential for the CuIII/CuII couple, thus allowing easy oxidation of the coordinated copper(II) by atmospheric oxygen.

Gold(III) dithiocarbamate derivatives for the treatment of cancer: solution chemistry, DNA binding, and hemolytic properties.

Gold(III) compounds are emerging as a new class of metal complexes with outstanding cytotoxic properties and are presently being evaluated as potential antitumor agents. We report here on the solution and electrochemical properties, and the biological behavior of some gold(III) dithiocarbamate derivatives which have been recently proved to be one to 4 orders of magnitude more cytotoxic in vitro than the reference drug (cisplatin) and to be able to overcome to a large extent both intrinsic and acquired resistance to cisplatin itself. Their solution properties have been monitored in order to study their stability under physiological conditions; remarkably, they have shown to undergo complete hydrolysis within 1 h, the metal center remaining in the +3 oxidation state. Their DNA binding properties and ability in hemolyzing red blood cells have been also evaluated. These gold(III) complexes show high reactivity toward some biologically important isolated macromolecules, resulting in a dramatic inhibition of both DNA and RNA synthesis and inducing DNA lesions with a faster kinetics than cisplatin. Nevertheless, they also induce a strong and fast hemolytic effect (compared to cisplatin), suggesting that intracellular DNA might not represent their primary or exclusive biological target.

Electronic properties of mononuclear, dinuclear, and polynuclear cobaltacarboranes: electrochemical and spectroelectrochemical studies.

Electronic interactions and metal-metal communication in a wide range of cobaltacarborane-hydrocarbon complexes containing one to six metal centers, and exhibiting a variety of modes of inter-cage connectivity and molecular architectures, have been investigated via cyclic voltammetry, controlled potential coulometry, and UV-visible spectroelectrochemistry. The properties of mixed-valent Co(III)/Co(IV) and Co(II)/Co(III) species that are generated on oxidation or reduction of dinuclear and polynuclear Co(III) complexes were examined and classified as Robin-Day Class I (localized), Class II (partially delocalized), or Class III (fully delocalized) systems. The extent of metal-metal communication between metallacarborane cage units is strongly influenced by the type of intercage connection (e.g., cage B-B or Cp-Cp); the vertexes involved (equatorial vs apical); the nature of the linking unit, if any; and the presence of substituents on the carborane cages. In multi-tripledecker complexes where three CpCo(C(2)B(3)H(4))CoCp units are linked through a central triethynyl benzene connector, the data suggest that Co-Co electronic communication is extensive (Class III) within individual sandwich units while intersandwich delocalization is weak or absent. An extended Hückel study of CpCoC(2)B(4)H(6) double-decker and CpCo(C(2)B(3)H(5))CoCp triple-decker sandwich model complexes shows significant differences in the orbital contributions involved in the HOMO and LUMO of the former vs the latter type. The calculations afford additional insight into the electronic structures and properties of these systems as elucidated by the experimental studies.

Synthesis, structural characterization, solution chemistry, and preliminary biological studies of the ruthenium(III) complexes [TzH][trans-RuCl4(Tz)2] and [TzH][trans-RuCl4(DMSO)(Tz)].(DMSO), the thiazole analogues of antitumor ICR and NAMI-A.

Two ruthenium(III) complexes bearing the thiazole ligand, namely, thiazolium (bisthiazole) tetrachlororuthenate (I, TzICR) and thiazolium (thiazole, DMSO) tetrachlororuthenate (II, TzNAMI) were prepared and characterized. The crystal structures of both complexes were solved by X-ray diffraction methods and found to match closely those of the corresponding imidazole complexes. The behavior in aqueous solution of bothTzICR and TzNAMI was analyzed spectroscopically. The time-dependent spectrophotometric profiles resemble closely those of the related ICR and NAMI-A anticancer compounds, respectively. It is observed that replacement of imidazole with thiazole, a less basic ligand, produces a significant decrease of the ligand exchange rates in the case of the NAMI-like compound. The main electrochemical features of these ruthenium(III) thiazole complexes were determined and compared to those of ICR and NAMI-A. Moreover, some preliminary data were obtained on their biological properties. Notably, both complexes exhibit higher reactivity toward serum albumin than toward calf thymus DNA; cytotoxicity is negligible in line with expectations. A more extensive characterization of the pharmacological properties in vivo is presently in progress.

Study of ruthenium(II) complexes with anticancer drugs as ligands. Design of metal-based phototherapeutic agents.

The reaction of trans-[RuCl(2)(PPh(3))(3)] (Ph = C(6)H(5)) with 2-thio-1,3-pyrimidine (HTPYM) and 6-thiopurines (TPs) produced mainly crystalline solids that consist of cis,cis,trans-[Ru(PPh(3))(2)(N,S-TPYM)(2)] (1) and cis,cis,trans-[Ru(PPh(3))(2)(N(7),S-TPs)(2)]X(2) (X = Cl(-), CF(3)SO(3)(-)). In the case of TPs, other coordination isomers have never been isolated and reported. Instead, the mother liquor obtained after filtration of 1 produced red single crystals of trans,cis,cis-[Ru(PPh(3))(2)(N,S-TPYM)(2)].2H(3)O(+).2Cl(-) (2.2H(3)O(+).2Cl(-)). Selected ruthenium(II)-thiobase complexes were studied for their structural, reactivity, spectroscopic, redox, and cytotoxic properties. Single crystals of 1 contain thiopyrimidinato anions chelated to the metal center via N and S. The Ru[bond]N bonds are significantly elongated for 1 [2.122(2) and 2.167(2) A] with respect to 2 [2.063(3) A] because of the trans influence from PPh(3). The coordination pseudo-octahedron for 2 is significantly elongated at the apical sites (PPh(3) ligands). Solutions of cis,cis,trans isomers in air are stable for weeks, whereas those of 2 turn green within 24 h, in agreement with the respective redox potentials. cis,cis,trans- and trans,cis,cis-[Ru(PH(3))(2)(N,S-TPYM)(2)], as optimized through the DFT methods at the Becke3LYP level are in good agreement with experimental geometrical parameters (1 and 2), with cis,cis,trans being more stable than trans,cis,cis by 3.88 kcal. The trend is confirmed by molecular modeling based on semiempirical (ZINDO/1) and molecular mechanics (MM) methods. Cytotoxic activity measurements for cis,cis,trans-[Ru(PPh(3))(N-THZ)(N(7),S -H(2)TP)(2)]Cl(2) (4) (THZ = thiazole, H(2)TP = 6-thiopurine) and cis,cis,trans-[Ru(PPh(3))(2)(N(7),S-HTPR)2]Cl(2) (5) (HTPR = 6-thiopurine riboside) against ovarian cancer cells A2780/S gave IC(50) values of 17 +/- 1 and 29 +/- 9 microM, respectively. Furthermore, the spectral analysis of HTPYM, TPs, and their Ru(II) complexes in solution shows that intense absorptions occur in the UVA/vis region of light, whereas standard nucleobases absorb in the UVB region.

A complete family of isostructural cluster compounds with cubane-like M(3)S(4)M' cores (M = Mo, W; M' = Ni, Pd, Pt): comparative crystallography and electrochemistry.

By reaction of the geometrically incomplete cubane-like clusters [(eta(5)-Cp')(3)Mo(3)S(4))][pts] and [(eta(5)-Cp')(3)W(3)S(4)][pts] (Cp' = methylcyclopentadienyl; pts = p-toluenesulfonate) with group 10 alkene complexes, three new heterobimetallic clusters with cubane-like cluster cores were isolated: [(eta(5)-Cp')(3)W(3)S(4)M'(PPh(3))][pts] ([5][pts], M' = Pd; [6][pts], M' = Pt); [(eta(5)-Cp')(3)Mo(3)S(4)Ni(AsPh(3))][pts] ([7][pts]). The compounds [5][pts]-[7][pts] are completing the extensive series of clusters [(eta(5)-Cp')(3)M(3)S(4)M'(EPh(3))][pts] (M = Mo, W; M' = Ni, Pd, Pt; E = P, As) which allows the consequences of replacing a single type of atom on structural and NMR and UV/vis spectroscopic as well as electrochemical properties to be determined. Single-crystal X-ray structure determinations of [5][pts]-[7][pts] revealed that [5][pts] was not isomorphous to the other members of the series [(eta(5)-Cp')(3)M(3)S(4)M'(EPh(3))][pts] due to distinctly different cell parameters, which in the molecular structure of [5](+) is reflected in a slightly different orientation of the PPh(3) ligand. Electrochemical measurements on the series showed that the Mo-based clusters were more difficult to oxidize than their W-based analogues. The Pd-containing clusters underwent two-electron oxidation processes, whereas the Ni- and Pt-containing clusters underwent two separated one-electron oxidation processes.

3,3-Diethyl-and 3,3-dibenzyl-1,2-diferrocenylcyclopropenes.

Reactions of 2,3-diferrocenylcyclopropenone 1 with ethyl- and benzylmagnesium chlorides afford 3,3-diethyl-and 3,3-dibenzyl- 1,2-diferrocenylcyclopropenes 2 and 3, respectively, and products of nucleophilic opening of the three-membered ring resulting from the addition of RMgCl to the carbonyl group, viz., saturated ketones(4,5-diferrocenylheptan-3-ones 4a,b and 3,4-diferrocenyl-1,5-diphenylpentan-2-ones 5a,b as ca. 3: 1 mixtures of two diastereomers) and other products. The spatial structures of compounds 2 and 4a were established by X-ray diffraction analysis of single crystals. Protonation of the cyclopropenes 2 and 3 with tetrafluoroboric acid at -40 degrees C yields the corresponding 3,3-dialkyl-1 ,2-diferrocenylcyclopropylium tetrafluoroborates. Transformation of the latter into diferrocenylallylic cations upon increasing the temperature to 20 degrees C and their eprotonation under the action of N,N-dimethylaniline were studied. Electrochemical investigation of 1 and 2 shows that in both complexes the cyclopropene spacer allows electronic communication between the two outer ferrocenyl groups, this being notably greater for 2 than for 1.