A Novel Cytotoxic Cerium Complex: Aquatrichloridobis(1,10‐phenanthroline)cerium(III) (KP776). Synthesis,Characterization, Behavior in H2O,Binding towards Biomolecules,and Antiproliferative Activity

The lanthanide complex aquatrichloridobis(1,10‐phenanthroline)cerium(III) [Ce(phen)₂(H₂O)Cl₃] (KP776) was fully characterized by elemental analysis, IR‐, and ¹H‐ and ¹³C‐NMR spectroscopy, as well as TG/DTA measurements, and its behavior in H₂O, important for the application as a chemotherapeutic, was studied. In addition, the binding of KP776 to nucleotides and single serum proteins was investigated by capillary electrophoresis, whereas binding to proteins in human plasma was observed by ICP‐MS. The compound shows promising anticancer properties in vitro: proliferation of human cancer cell lines is strongly inhibited with IC₅₀ values in the very low micromolar range.     

Copper(II) complexes with 2-N-(picolinylidene)-n-R-phenols: Solvatochromism, self-assembly and supramolecular structures

A series of copper(II) complexes having the formula [Cu(n-R-pyp)X] with the N,N,O-donor Schiff base system 2-N-(picolinylidene)-n-R-phenol (n-R-Hpyp) (where n = 3, 4, 5 and 6, when R = Me and n = 4 when R = Cl) and halide (X⁻ = Cl⁻ or Br⁻) as an ancillary ligand have been synthesized. The complexes are characterized by microanalytical, magnetic and various spectroscopic measurements. They display solvatochromic behavior. Single crystal X-ray structures of all the complexes are determined. In coordinatively unsaturated species such as a square-planar complex, the metal ion can interact with a fifth atom and if this atom is metal bound, dimeric or polymeric aggregate is formed. In the present series of complexes, the metal ions are square-planar and distorted square-pyramidal when there is an intermolecular Cu···X interaction. In addition to this Cu···X interaction, presence of intermolecular weak non-covalent interactions namely O-H···O, C-H···O, C-H···X and π···π are perceived. The supramolecular architectures formed by the molecules of these complexes via these interactions are scrutinized. The observed supramolecular structural motifs can be classified as staircase, ladder, brick-wall and square-grid. Except for R = Cl the analogous chloride and bromide coordinated complexes show similar structural features.     

Structural studies on [Mo3S4] and [Mo3S4Cu] complexes with tripodal ligands providing various NxOy (x + Y = 3) donor sets

The interaction of 1,3,5-triamino-1,3,5-trideoxy-cis-inositol (taci) and its N-methylated derivative 1,3,5-trideoxy-1,3,5-tris(dimethylamino)-cis-inositol (tdci) with the incomplete [Mo₃S₄]⁴⁺ cube and the heterometallic [Mo₃S₄Cu]⁴⁺ cube have been investigated by X-ray analysis. The crystal structures of [Mo₃S₄(taci+ rmC₃H₆O-H₂O)₃-4H]·2OH₂O (1a, rhombohedral, space group R32, A = 15.964(3), C = 40.59(1) Å, Z = 6), [Mo₃S₄(tdci)₃]Br₄·9.5EtOH·5H₂O (2a, triclinic, space group

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and [CuBrMo₃S₄(tdci)₃]Br₃·11 H₂O·EtOH (3a, monoclinic, space group P2,/n, A = 14.887(3), B = 22.570(4), C = 21.974(5) Å, β = 98.54(2)°, Z = 4) revealed andN-N-O and an N-O-O coordination mode for taci and tdci, respectively. In 1a, taci is coordinated as an anion with deprotonated oxygen and nitrogen donors. In addition, the non-coordinating amino group reacted with one equivalent; of acetone, forming a Schiff base condensation product. For 2a, short Mo---O bonds and high pK_a values (compared to the aqua ion [Mo₃S₄(H₂O)₉]⁴⁺) indicate the formation of a zwitterionic form of the tdci ligand with coordinated alkoxo groups and peripheral dimethylammonium groups. No significant differences were found for the structural properties of the Mo-tdci fragment in 2a and 3a. The coordination modes of taci and tdci, as observed in the solid state, are in agreement with the previously reported solution structures, established by NMR spectroscopy. They are attributed to the specific steric requirements of the two ligands and to a pronounced preference of the [Mo₃(μS)₃(μ₃S)]⁴⁺ core to coordinate a nitrogen donor trans to μ₃S.     

Simultaneous determination of thermodynamic and kinetic parameters of aminopolycarbonate complexes of cobalt(II) and nickel(II) based on isothermal titration calorimetry data

The influence of the different side chain residues on the thermodynamic and kinetic parameters for complexation reactions of the Co²⁺ and Ni²⁺ ions has been investigated by using the isothermal titration calorimetry (ITC) technique supported by potentiometric titration data. The study was concerned with the 2 common tripodal aminocarboxylate ligands, namely, nitrilotriacetic acid and N‐(2‐hydroxyethyl) iminodiacetic acid. Calorimetric measurements (ITC) were run in the 2‐(N‐morpholino)ethanesulfonic acid hydrate (2‐(N‐morpholino) ethanesulfonic acid), piperazine‐N ,N ′‐bis(2‐ethanesulfonic acid), and dimethylarsenic acid buffers (0.1 mol L⁻¹, pH 6) at 298.15 K. The quantification of the metal‐buffer interactions and their incorporation into the ITC data analysis enabled to obtain the pH‐independent and buffer‐independent thermodynamic parameters (K , ΔG , ΔH , and ΔS ) for the reactions under study. Furthermore, the kinITC method was applied to obtain kinetic information on complexation reactions from the ITC data. Correlations, based on kinetic and thermodynamic data, between the kinetics of formation of Co²⁺ and Ni²⁺ complexes and their thermodynamic stabilities are discussed.     

4,5-Diazafluorene N-glycopyranosyl hydrazones as scaffolds for potential bioactive metallo-organic compounds: Synthesis,structural study and cytotoxic activity

A series of novel N¹-(4,5-diazafluoren-9-yliden)-N²-glycopyranosyl hydrazines was prepared in synthetically useful yields by treatment of 9H-4,5-diazafluoren-9-hydrazone with different unprotected monosaccharides. The reactions with the monosaccharides tested afforded stereoselectively, and exclusively, cyclic derivatives, whose structures correspond to N-β-glycopyranosyl hydrazones except for the d-arabinose derivative that agrees with the α-anomer. Several copper(II) complexes having a 2:1 ligand to metal mole ratio were also prepared. The metal complexes can bind DNA sequences and preferentially stabilize G-quadruplex DNA structures over dsDNA. The fucose, rhamnose and deoxyglucose copper(II) complexes exhibited a cytotoxic activity against cultured HeLa and PC3 tumor cells comparable to other metal complexes normally used for chemotherapeutic purposes, such as cisplatin.     

Proteomic Profiling Reveals the Molecular Control of Oocyte Maturation

Meiotic maturation is an intricate and precisely regulated process orchestrated by various pathways and numerous proteins. However, little is known about the proteome landscape during oocytes maturation. Here, we obtained the temporal proteomic profiles of mouse oocytes during in vivo maturation. We successfully quantified 4694 proteins from 4500 oocytes in three key stages (germinal vesicle, germinal vesicle breakdown, and metaphase II). In particular, we discovered the novel proteomic features during oocyte maturation, such as the active Skp1–Cullin–Fbox pathway and an increase in mRNA decay–related proteins. Using functional approaches, we further identified the key factors controlling the histone acetylation state in oocytes and the vital proteins modulating meiotic cell cycle. Taken together, our data serve as a broad resource on the dynamics occurring in oocyte proteome and provide important knowledge to better understand the molecular mechanisms during germ cell development.     

Synthesis and characterization of Sodium cis-dichlorochenodeoxycholylglycinato(O,N) platinum(II) – Cytostatic activity

With a view to using bile acids as shuttles for delivering platinum-related cytostatic drugs to liver tumors, a chenodeoxycholylglycinato(CDCG)-derivative of platinum(II) has been synthesized. The complex - named Bamet-M2- was chemically characterized by elemental analysis, FT-IR, NMR, FAB-MS, and UV spectroscopy. The results indicate the following composition: C₂₆H₄₂N₂O₅Cl₂NaPt(II), the metal Pt(II) being bound to two Cl^– and one bidentate CDCG moiety, i.e., Na[Pt CDCG(N,O) Cl₂]. The compound is highly soluble (up to 20 mM) in water and (up to 35 mM) in ethanol, methanol and DMSO. Hydrolysis was investigated because this is assumed to be an important step in intracellular activation and interaction with DNA of this type of compounds. The reaction kinetics of this complex in aqueous solution show unusual behaviour; the substitution process with the displacement of two Cl^– was almost instantaneous, and the resulting species were found to be very stable. Kinetic studies carried out in the presence of different NaCl concentrations (up to 500 mM) revealed similar fast and nonreversible aquations of Bamet-M2. This contrasts with the slow aquation of cisplatin in extracellular-line solutions (i.e., at high NaCl concentrations) as compared with fast hydrolysis in cells. This difference may partly account for the low cytostatic activity observed here for Bamet-M2 against several tumor cell-lines.     

Differentiation of the intracytoplasmic membrane of Rhodopseudomonas palustris induced by variations of oxygen partial pressure or light intensity

The photosynthetic apparatus of Rhodopseudomonas palustris contains, in addition to reaction center bacteriochlorophyll (Bchl) two spectral forms of light harvesting (LH) Bchl, i.e. LH Bchl I, characterized by an infrared absorption maximum at 880 nm (890 nm at 77°K) and LH Bchl II absorbing at 805 and 855 nm (805 and 870 nm at 77°K). LH Bchl I seems to be associated with a single protein species of an apparent mol. wt. of 13000 whereas LH Bchl II is apparently associated with two proteins of mol. wts. of 9000 and 11000.Cells in anaerobic cultures adapt to changes of light intensity 1. by variation of the size of the photosynthetic unit, i.e. the molar ratio of LH Bchl II to reaction center Bchl, 2. by variation of the number of photosynthetic units per unit of membrane area, 3. by regulation of the size of the intracytoplasmic membrane system.During adaptation of changes of oxygen partial pressure cells are able to synthesize reaction center Bchl, LH Bchl and intracytoplasmic membranes at different rates. The synthesis of reaction center Bchl and LH Bchl I are, however, coordinated with each other, while the syntheses of LH Bchl II and reaction center Bchl proceed independently.List of Non-Standard Abbreviations Bchl bacteriochlorophyll - ICM mitracytoplasmic membrane - LDAO lauryldimethyl aminoxide - R Rhodopseudomonas - RC reaction center - SDS sodium dodecylsulfate     

Proteasomes (prosomes) inhibit the translation of Tobacco mosaic virus RNA by preventing the formation of initiation complexes

Proteasomes (prosomes) are large multiprotein complexes. They are involved in protein degradation of ubiquitin-conjugated proteins and in the generation of MHC class I peptides. We gave further evidence that they interfere within vitro protein synthesis. Proteasomes inhibit the translation of Tobacco mosaic virus RNA. Analysis of cell-free systems by sucrose gradient centrifugation revealted that they prevent the formation of 80S initiation complexes but not the early phase of initiation.     

Effect of pH and the binding anion on In3+-transferrin interaction: spectroscopic study of the perturbed angular correlation of 172-245 keV gamma rays of indium 111

The formation of ternary complexes, transferrin-anion-In111 has been investigated by means of gamma-gamma coincidence spectrometry of the 172-245 keV rays. The angular correlation between the two gamma-rays emitted in cascade depends on the magnetic and electric fields gradients, consequently the chemical structure of metal holder. Any modification of this structure causes the variation of angular correlation. The study of G22 (infinity) as function of pH (G22(infinity): integrated perturbed angular correlation coefficient) has been performed to turn out the hydrolysis of In111 in aqueous solution, metal complex formation in presence of chelating agents (citric acid and sodium bicarbonate) and the formation of protein-metal complexes. The presence of complexing agents limits the domain of In111 colloid existence and allows fast transfer of ionised indium on the transferrin. Two types of metal-protein interactions has been turn out. The first in the weakly acidic range of pH is characterized by an affinity constant near to this of citric acid. The second lying in neutral and basic range of pH, where the formation rate of transferrin-In111 complex is fast (t less than 500 s). In citrate medium, for pH 6-7,5 the rate of metal transfer on the protein, studied by means of G22 (infinity) = f(t), is function of pH. The binding anion appears as an indispensable element for the formation of protein-metal complexes. The In111 previously chelated by 8-Hydroxyquinoline is fixed by the protein if only exits a binding anion in the solution. This mays bring in the formation of an intermediate active state, indispensable step for the ternary complex formation transferrin-anion-In111.