Antitumour Organometallics. III. In Vivo Activity of Diphenylantimony(III) and Diorganotin(IV) Dithiophosphorus Derivatives Against P388 Leukemia

Diphenylantimony(III) and diorganotin(IV) derivatives of dithiophosphorus ligands, i.e. Ph(2)SbS(2)PR'(2) (R' = Ph, OPr-i) and R(2)Sn(S(2)PR'(2))(2) (R = n-Bu, Ph, R' = Ph; R = Ph, R' = OPr-i), have been screened against P388 leukemia in mice. All the compounds showed marginal activity towards this tumor system, some of them increasing the life span of the animals with more than 20%. The best results were obtained with (di-iso-propylphosphorodithioato)diphenylantimony(III) which exhibited a T/C value of 136%, at a dose of 5 mg/kg, administered on days 1,2 and 3 after tumor transplantation.     

Mutational Consequences on Replication of M13 Constructs Containing Isomeric Diol Epoxide Adducts in E. coli

Eight isomeric dGuo and eight dAdo adducts resulting from cis and trans opening of each of the four optically active diol epoxides (DEs) derived from benzo[ a ]pyrene (B a P) and benzo[ c ]phenanthrene (B c Ph) were placed in each of two 16-mer DNA sequences to give 32 modified oligonucleotides, which were ligated into M13mp7L2 and allowed to replicate in SOS-induced Escherichia coli . The effects of parent hydrocarbon, adduct stereochemistry, and sequence context on mutagenic response are highly interdependent. B a P DE adducts are generally more mutagenic than the corresponding B c Ph adducts. The mutational frequency is generally larger for cis - relative to trans -opened DE adducts of both dGuo and dAdo. In a ～TA*G～ context, B c Ph DE dAdo adducts (A*) with R configuration at the site of attachment to the adenine base produced very few substitution mutations when compared with adducts having S configuration. This configurational effect is not observed for B a P DE dAdo adducts, nor for B a P or B c Ph dGuo adducts.     

Genotoxicity of Some Metal-Based Antineoplastics, Evaluated by SOS Chromotest and Cytogenetic Analysis

The paper reports the screening results of two metal-based antineoplastic drugs with mutagenic potential, such as Romcis (trademark of Cisplatinum, produced in Romania) and diphenylantimony(III) diisopropyldithiophosphate (PADTF). Their effects were compared with those induced by Cyclophosphamide. Two mutagenicity tests, the SOS Chromotest and cytogenetic analysis were applied. The tests were carried out with or without metabolic activation (addition of S(9)-mix), either in E. coli PQ 37 cultures, using four doses (0.3, 3, 30 and 300 pmol compound/assay) for the SOS Chromotest or in leukocyte cultures using 0.3 mM from each compound, for cytogenetics. The dose- response relationships and SOSIP values revealed an indirect mutagenic potential for Cyclophosphamide, amplified by S(9) mix in bacterial cultures and an antiproliferative, clastogenic effect on lymphocytes. For Romcis and diphenylantimony(III) diisopropyldithiophosphate, a significant positive response by SOS Chromotest was recorded, which correlated with increased frequencies of chromosomal aberrations.     

Removal of arsenic(III) from aqueous solution by concrete-based adsorbents

The present paper investigates the adsorption of arsenic(III) (As(III)) onto 2 concrete-based low-cost materials, i.e., Aerocrete and Vermiculite impregnated by ferric oxyhydroxide. Adsorption experiments were performed to study the effect of initial pH, initial concentration of As(III), contact time, and ions usually present in water. No significant effect of the initial pH on the adsorption of As(III) by Aerocrete and Vermiculite was observed at the pH range of 4–8. The As(III) removal efficiency decreased at a high initial pH (i.e., 10). The Langmuir isotherm showed that the maximum As(III) adsorption capacity of Aerocrete and Vermiculite is 15.15 and 13.51 mg/g, respectively, which is higher than that observed using titanium dioxide (i.e., 3.52 mg/g), at pH 7 and 24 ±1 °C. A pseudo-second order kinetic model fitted well the experimentally obtained kinetic data. This suggests that chemisorption most probably controls the adsorption of As(III) on Aeroctere and Vermiculite. Significantly, As(III) (1 mg/L) could be removed almost completely by both Aeroctere and Vermiculite (1 g/L) in 30 and 60 min, respectively at pH 7 and 24 ±1 °C. Importantly, Ca²⁺, Mg²⁺, Na⁺, HCO₃⁻, SO₄²⁻, and Cl⁻ ions had no significant effect on the adsorption of As(III) on Aeroctere and Vermiculite. The results showed that the proposed concrete-based adsorbents have the potential to remove As(III) from water.     

Anticancer Potential of (Pentamethylcyclopentadienyl)chloridoiridium(III) Complexes Bearing κP and κP,κS‐Coordinated Ph2PCH2CH2CH2S(O)xPh (x=0–2) Ligands

Iridium(III) complexes of the type [Ir(η⁵‐C₅Me₅)Cl₂{Ph₂PCH₂CH₂CH₂S(O)_xPh‐κP}] (x=0–2; 1 – 3 ) and [Ir(η⁵‐C₅Me₅)Cl{Ph₂PCH₂CH₂CH₂S(O)_xPh‐κP,κS}][PF₆] (x=0–1; 4 and 5 ) with 3‐(diphenylphosphino)propyl phenyl sulfide, sulfoxide, and sulfone ligands Ph₂PCH₂CH₂CH₂S(O)_xPh were designed, synthesized, and characterized fully, including X‐ray diffraction analyses for complexes 3 and 4 . In vitro studies against human thyroid carcinoma (8505C), submandibular carcinoma (A253), breast adenocarcinoma (MCF‐7), colon adenocarcinoma (SW480), and melanoma (518A2) cell lines provided evidence for the high biological potential of the neutral and cationic iridium(III) complexes. Neutral iridium(III) complex 5 proved to be the most active, with IC₅₀ values up to about 0.1 μM , representing activities of up to one order of magnitude higher than cisplatin. Using 8505C cells, apoptosis was shown to be the main mechanism through which complex 5 exerts its tumoricidal action. The described iridium(III) complexes represent potential leads in the search for novel metal‐based anticancer agents.     

Analysis of the linear methods for determining copolymerization reactivity ratios,VIII. A critical reexamination of radical copolymerization of methylmethacrylate or styrene

The reactivity ratios of selected methylmethacrylate or styrene copolymerisation systems have been reviewed in terms of the extended Kelen-Tüd?s method. r-values, together with their 95% confidence limits have been calculated. Quantities δ and Q, suitable for classification of the systems, have been applied. Of the 71 reevaluated methylmethacrylate systems 40 (56.3%) were found to belong to class I and 20 (28.2%) to class I(!), i. e. 60 (84.5%) systems for which the conventional copolymerisation equation was found to be adequate. For 3 (4.2%) systems belonging to class II the two-parameter model does not hold and 8 (11.3%) systems were related to class III, i. e. systems for which the experimental data are inconsistent and the published r-values meaningless. 32 styrene copolymerisation systems were reevaluated with the following classification: 19 (59.4%) systems in class I, 5 (15.6%) systems in class I(!), 2 systems in class II and 6 (18.8%) in class III.     

Process control of polymer extrusion. Part I: Feedback control

On-line computer control of extrudate thickness was carried out using a 2–1/2 Inch single screw plasticating extruder. Predried poly(methyl methacrylate) (PMMA) was extruded through a slit die. Two feedback control methods, a conventional PI controller and a Smith predictor dead time compensation, were tried for both set point changes (i. e., extrudate thickness changes) and load changes (i. e., screw speed changes). Results showed that both the PI feedback control and the Smith predictor were satisfactory for long term set point changes but not for load changes. Since the Smith predictor may compensate the process dead time, it would be useful for regulating short term set point changes such as barrel temperature settings.     

The Structures of Gd(III) Chelates Conjugated at the Periphery of 3-(1’-Hexyloxy)ethyl-3-devinylpyropheophorbide-a (HPPH) Have a Significant Impact on the Imaging and Therapy of Cancer

3-(1’-Hexyloxyethyl)-3-devinyl-pyropheophorbide-a (HPPH or Photochlor), a tumor-avid chlorophyll-a derivative currently undergoing human clinical trials, was conjugated at various peripheral positions (position-17 or 20) of HPPH with either Gd(III)-aminobenzyl-DTPA (Gd(III) DTPA) or Gd(III)-aminoethylamido-DOTA (Gd(III) DOTA). The corresponding conjugates were evaluated for in vitro PDT efficacy, T₁, T₂ relaxivities, in vivo fluorescence, and MR imaging under similar treatment parameters. Among these analogs, the water-soluble Gd(III)-aminoethylamido-DOTA linked at position-17 of HPPH, i. e., HPPH-17-Gd(III) DOTA, demonstrated strong potential for tumor imaging by both MR and fluorescence, while maintaining the PDT efficacy in BALB/c mice bearing Colon-26 tumors (7/10 mice were tumor free on day 60). In contrast to Gd(III) DTPA (Magnevist) and Gd(III) DOTA (Dotarem), the HPPH-Gd(III) DOTA retains in the tumor for a long period of time (24 to 48 h) and provides an option of fluorescence-guided cancer therapy. Thus, a single agent can be used for cancer-imaging and therapy. However, further detailed pharmacokinetic, pharmacodynamic, and toxicological studies of the conjugate are required before initiating Phase I human clinical trials.     

Controlled reduction for size selective synthesis of thiolate-protected gold nanoclusters Aun (n = 20, 24, 39, 40)

ABSTRACT: This work presents a controlled reduction method for the selective synthesis of different sized gold nanoclusters protected by thiolate (SR = SC2H4Ph). Starting with Au(III) salt, all the syntheses of Aun(SR)m nanoclusters with (n, m) = (20, 16), (24, 20), (39, 29), and (40, 30) necessitate experimental conditions of slow stirring and slow reduction of Au(I) intermediate species. By controlling the reaction kinetics for the reduction of Au(I) into clusters by NaBH4, different sized gold nanoclusters are selectively obtained. Two factors are identified to be important for the selective growth of Au20, Au24, and Au39/40 nanoclusters, including the stirring speed of the Au(I) solution and the NaBH4 addition speed during the step of Au(I) reduction to clusters. When comparing with the synthesis of Au25(SC2H4Ph)18 nanoclusters, we further identified that the reduction degree of Au(I) by NaBH4 also plays an important role in controlling cluster size. Overall, our results demonstrate the feasibility of attaining new sizes of gold nanoclusters via a controlled reduction route.     

Nanofiltration Membrane Process for the Removal of Arsenic from Drinking Water

The removal of arsenic from drinking water by nanofiltration membranes was investigated. Experiments were conducted with tap water to which arsenate and arsenite were added. Two types of nanofiltration membranes, i.e., NF‐90 and NF‐200, have been tested. The effect of various operating conditions, e.g., applied pressure, feed concentration, pH and temperature, were also investigated. The pH and arsenic concentration in the feed and the operating temperature are found to be decisive factors in determining the arsenic concentration remaining in the permeate. The level of removal of As(V) was higher than 98 % for both membranes, but that of As(III) was much lower. It can be concluded that by controlling the operating parameters, source water containing As(V) may be recovered as drinking water to EPA maximum contaminant level quality standards, but that water containing As(III) must undergo a pre‐oxidation treatment before passing through the nanofiltration membrane in order to maintain drinking water quality.     

A topological sub-structural approach to the mutagenic activity in dental monomers. 3. Heterogeneous set of compounds

The topological sub-structural molecular design (TOPS-MODE) approach has been applied to the study of mutagenic properties in a heterogeneous set of dental monomers. A model able to describe close to 90% of the experimental variance in the values for mutagenic activity of 41 dental monomers through genetic algorithm was developed with the use of the mentioned approach. Also, a study for the determination of the optimal number of variables in the equation and potential outliers was carried out. Finally, the TOPS-MODE approach was used to derive the contribution of different fragments to the mutagenic activity.     

Vitrigens. I. Synthesis and Characterization of Low Molecular Weight Organic Glasses

New low molecular weight organic materials with a strong tendency towards glass formation and glass temperatures above room temperature were synthesized. These materials consist of twin molecules where two bulky groups, i.e. carbazole ( Ca ), 3,6-dibromocarbazole ( DbrCa ), 2,3-benzocarbazole ( BC ), 1,2-benzo-3,4-dihydrocarbazole ( BCDH ), phenothiazine ( Ph ), 1,8-naphthalic acid anhydride ( NI ), and pyrene-1-aldehyde ( PY ) have been linked by flexible or semi-flexible aliphatic or aromatic central units. Their structure-glass temperature relationship and some relations between thermodynamic parameters and amorphous properties are discussed.     

Stoichiometric Reductive C?N Bond Formation of Arylgold(III) Complexes with N‐Nucleophiles

The reductive formation of substituted anilines from amines and three well‐defined aryl‐ gold(III) complexes, i.e., dichloro(2,6‐lutidine)phen‐ ylgold(III) ( 2 ), dichloro(2,6‐lutidine)‐p‐tolylgold(III) ( 3 ), and chlorobis(triphenylphosphine)phenylgold(III) chloride ( 4 ) was studied. The reaction is stoichiometric in gold and represents a key step of a potential gold‐catalyzed intermolecular amination reaction of arenes. It proceeds smoothly with a broad range of N‐nucleophiles in the presence of sodium acetate (NaOAc) and enables the selective formation of N‐substituted anilines in good yields. A mechanistic pathway is proposed and discussed as well.     

Synthesis and properties of hydrophilic polymers. III. Ligand effects of the side chains of polyaziridines on metal complexation in aqueous solution

The metal-complexing properties of five different polyaziridines—poly[1-(2-aminoethyl)aziridine], poly(1-acetylaziridine), poly[1-(2-hydroxyethyl)aziridine], poly[1-(2-hydroxyethyl)aziridine-co-1-acetylaziridine], and poly[1-(2-aminoethyl)aziridine] oxine—were investigated in an aqueous solution with regard to the side-chain effects using membrane filtration. The results are discussed and compared with the stability constants of metalcomplexation of the corresponding functional moieties. Poly[1-(2-aminoethyl)aziridine], a poly(aziridine) with neutral nitrogen donors in the side chains, showed similar complexing properties to those of ammonia. The only exceptions are Fe(III) and Cr(III), which cannot form complexes with ammonia but can be retained in the membrane filtration process due to the formation of Fe(III)-colloidal species and hydroxides. The complexing properties of polyaziridines containing hydroxyl groups in the side chains (i.e., poly[1-(2-hydroxyethyl)aziridine] and poly[1-(2-hydroxyethyl) aziridine-co-1-acetylaziridine] can be explained and described by the formation constants with the corresponding hydroxides. The introduction of a carbonyl moiety in the polyaziridine side chain, e.g., polyacetylaziridine, reduces the complexing ability for metal ions because the carbonyl group cannot form complexes with the metal ions investigated. Poly[1-(2-aminoethyl)aziridine]oxine showed the strongest complexing ability in the series of metal ions due to the strong complexing ligand 8-hydroxy quinoline attached to the polymer backbone. © 1996 John Wiley & Sons, Inc.     

Low-Temperature Synthesis and Characterization of Mixed Sodium Cerium(III) Hexa-Aluminate

Two forms of sodium cerium(III) mixed hexa-aluminate were prepared at temperature as low as 1270°C, i.e., 300°C lower than those reported previously, and characterized by X-ray diffraction techniques. These compounds are formed by thermal treatment, under argon, of an amorphous organometallic precursor obtained by the "citric acid method". During the synthesis, the 3+ oxidation state of cerium is retained at all temperatures.     

Iron(III) protoporphyrin IX—single-wall carbon nanotubes modified electrodes for hydrogen peroxide and nitrite detection

Iron(III) protoporphyrin IX (Fe(III)P), adsorbed either on single-walled carbon nanotubes (SWCNT) or on hydroxyl-functionalized SWCNT (SWCNT-OH), was incorporated within a Nafion matrix immobilized on the surface of a graphite electrode. From cyclic voltammetric measurements, performed under different experimental conditions (pH and potential scan rate), it was established that the Fe(III)P/Fe(II)P redox couple involves 1e⁻/1H⁺. The heterogeneous electron transfer process occurred faster when Fe(III)P was adsorbed on SWCNT-OH (11 s⁻¹) than on SWCNT (4.9 s⁻¹). Both the SWCNT-Fe(III)P- and SWCNT-OH-Fe(III)P-modified graphite electrodes exhibit electrocatalytic activity for H₂O₂ and nitrite reduction. The modified electrodes sensitivities were found varying in the following sequences: S_{SWCNT-OH-Fe(III)P} = 2.45 mA/M ≈ S_{SWCNT-Fe(III)P} = 2.95 mA/M > S_Fe(III)P = 1.34 mA/M for H₂O₂, and S_{SWCNT-Fe(III)P} = 3.54 mA/M > S_Fe(III)P = 1.44 mA/M > S_{SWCNT-OH-Fe(III)P} = 0.81 mA/M for NO₂⁻.     

Thermoplastic vulcanizates based on epoxidized natural rubber/polypropylene blends: Effect of compatibilizers and reactive blending

Epoxidized natural rubber (ENR) was prepared using the performic epoxidation method. TPVs based on ENR/PP blends were later prepared by melt‐mixing processes via dynamic vulcanization. The effects of blend ratios of ENR/PP, types of compatibilizers, and reactive blending were investigated. Phenolic modified polypropylene (Ph‐PP) and graft copolymer of maleic anhydride on polypropylene molecules (PP‐g‐MA) were prepared and used as blend compatibilizers and reactive blending components of ENR/Ph‐PP and ENR/PP‐g‐MA blends. It was found that the mixing torque, apparent shear stress and apparent shear viscosity increased with increasing levels of ENR. This is attributed to the higher viscosity of the pure ENR than that of the pure PP. Furthermore, there was a higher compatibilizing effect because of the chemical interaction between the polar groups in ENR and PP‐g‐MA or Ph‐PP. Mixing torque, shear flow properties (i.e., shear stress and shear viscosity) and mechanical properties (i.e., tensile strength, elongation at break, and hardness) of the TPVs prepared by reactive blending of ENR/Ph‐PP and ENR/PP‐g‐MA were lower than that of the samples without a compatibilizer. However, the TPVs prepared using Ph‐PP and PP‐g‐MA as compatibilizers exhibited higher values. We observed that the TPVs prepared from ENR/PP with Ph‐PP as a compatibilizer gave the highest rheological and mechanical properties, while the reactive blending of ENR/PP exhibited the lowest values. Trend of the properties corresponds to the morphology of the TPVs. That is, the TPV with Ph‐PP as a blend compatibilizer showed the smallest rubber particles dispersed in the PP matrix, while the reactive blending of ENR/PP‐g‐MA showed the largest particles. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 4729–4740, 2006     

Synergistic Solvent Extraction of Lanthanides(III) with Mixtures of 4-benzoyl-3-methyl-1-phenylpyrazol-5-one and Some Novel Carbamoyl- and Phosphorylmethoxymethylphosphine Oxides

The solvent extraction of La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, and Y from weak acidic hydrochloric acid solutions into an organic phase containing 4-benzoyl-3-methyl-1-phenylpyrazol-5-one (HP) and neutral tridentate organophosphorus ligands R₂P(O)CH₂OCH₂C(O)NBu₂ R = Bu (I), R = Ph (II) and R₂P(O)CH₂OCH₂P(O)R¹₂ R = R¹ = Bu (III); R = Bu, R¹ = Ph (IV); R = R¹ = Ph(V) has been studied. A considerable synergistic effect was observed in the presence of HP in the organic phase containing tetraoctyldiglycolamide (TODGA) and neutral organophosphorus ligands I - V. A successive replacement of C(O)NAlk₂ groups in the diglycolamide extractant molecule by P(O)Ph₂ groups leads to an increase in the extraction efficiency of Ln(III) ions when toluene was used as diluent. Phosphoryl-containing podand I possess a higher extraction efficiency towards Ln(III) ions than TODGA. The extraction equilibrium was investigated and the equilibrium constants were calculated. It was found that the lanthanide(III) ions are extracted as LnLP₃ and LnL₂P₃ complexes with mixtures of HP and I in toluene from weak acidic solutions.     

Parthenogenesis,calling behavior,and insect-released volatiles of leafminer moth Phyllonorycter emberizaepenella

We proved that the leafminer moth Phyllonorycter emberizaepenella (Lepidoptera: Gracillariidae) reproduces by parthenogenesis of the thelytoky type. Despite a complete absence of males, parthenogenetically reproducing females diurnally demonstrated the calling posture normally used for releasing signaling compounds. Two compounds, which we collected from a calling female, were identified as potential sex pheromone components: (8E,10E)-8,10-tetradecadienyl acetate and (8E,10E)-8,10-tetradecadienol, the latter occurring only in trace amounts. In field experiments, no males were attracted to traps baited with either the potential sex pheromone or with virgin females. Both the pattern of behavior and the chemical characteristics of the pheromone of Ph. emberizaepenella species were similar to those known for Lepidoptera with the usual amphimictic mode of reproduction. Theoretical speculations that in thelytoky, where there is no need to find a sexual partner, the individuals would obtain certain advantages due to reduction in their sexual behavior, were, thus, not confirmed for Ph. emberizaepenella.     

Enol cation radicals in solution. 4. An improved Synthesis of 4,6,7-Trimethylbenzofurans by oxidation of β-mesityl substituted enols

An improved synthetic access for the construction of 4,6,7-trimethylbenzofurans ( B1–B8 ) through the one-electron oxidation of mesityl-substituted enols ( E1–E8 ) is presented. The transformation can be accomplished in good to excellent yields by using various oxidants; i.e. tris(1,10-phenanthroline)iron(III) hexafluorophosphate, FeCl₃, Ce(NH₄)₂(NO₃)₆, Cu(OTf)₂/Cu₂O or anodic oxidation.