ɛ‐caprolactone and lactide polymerization promoted by an ionic titanium(IV)/iron(III) polynuclear halo‐alkoxide

The ionic [Ti₃(µ₃‐OPrⁱ)₂(µ‐OPrⁱ)₃(OPrⁱ)₆][FeCl₄] halo‐alkoxide ( A ) was investigated for its activity towards the bulk polymerization of rac‐lactide (rac‐LA) and ?‐caprolactone (?‐CL) in various temperatures, monomer/ A molar proportions, and reaction times. The reactivity of A in the ring‐opening polymerization (ROP) of both monomers is mainly due to the cationic [Ti₃(OPrⁱ)₁₁]⁺ unity and proceeds through the coordination–insertion mechanism. Molecular weights ranging from 6,379 to 13,950 g mol^?1 and PDI values varying from 1.22 to 1.52 were obtained. Results of ROP kinetic studies for both ?‐CL and rac‐LA confirm that the reaction rates are first‐order with respect to monomers. The production of poly(?‐caprolactone) shows a higher sensitivity of the reaction rate to temperature, while the polymerization of rac‐LA is slower and more dependent on the thermal stability of the active species during the propagation step. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2509–2517     

An electrochemical study of antineoplastic gallium, iron and ruthenium complexes with redox noninnocent alpha-N-heterocyclic chalcogensemicarbazones

The electrochemical properties of a series of alpha-N-heterocyclic chalcogensemicarbazones (HL), namely, thiosemicarbazones, selenosemicarbazones, and semicarbazones, and their gallium(III), iron(III), and ruthenium(III) complexes with the general formula [ML(2)][Y] (M = Ga, Fe or Ru; Y = PF(6)(-), NO(3)(-), or FeCl(4)(-)) were studied by cyclic voltammetry. The novel compounds were characterized by elemental analysis, a number of spectroscopic methods (NMR, UV-vis, IR), mass spectrometry and by X-ray crystallography. All complexes show several, mostly reversible, redox waves attributable to the reduction of the noninnocent chalcogensemicarbazone ligands at lower potentials (<-0.4 V vs NHE) than the metal-centered iron or ruthenium redox waves (>0 V vs NHE) in organic electrolyte solutions. The cyclic voltammograms of the gallium complexes display at least two consecutive reversible one-electron reduction waves. These reductions are shifted by approximately 0.6 V to lower potentials in the corresponding iron and ruthenium complexes. The electrochemical, chemical, and spectroscopic data indicate that the ligand-centered reduction takes place at the CH(3)CN double bond. Quantum chemical calculations on the geometric and electronic structures of 2-acetylpyridine (4)N,(4)N-dimethylthiosemicarbazone (HL(B)), the corresponding metal complexes [Ga(L(B))(2)](+) and [Fe(II)(L(B))(2)], and the one-electron reduction product for each of these species support the assignment of the reduction site and elucidate the observed order of the ligand-centered redox potentials, E(1/2)([Fe(II)(L)(2)]) < E(1/2)(HL) < E(1/2)([Ga(L)(2)](+)). The influence of water on the redox potentials of the complexes is reported and the physiological relevance of the electrochemical data for cytotoxicity as well as for ribonucleotide reductase inhibitory capacity are discussed.     

Mono-carboxylated diaminedichloridoplatinum(IV) complexes--selective synthesis, characterization, and cytotoxicity

(OC-6-43)-Dichlorido(N,N-dimethyl-ethane-1,2-diamine)dihydroxidoplatinum(IV) could selectively be mono-carboxylated with succinic anhydride based on the steric hindrance caused by the two methyl groups of the equatorial ligand. Subsequent esterification of the uncoordinated carboxylic acid with alcohols of different lengths (methanol, butanol, hexanol and octanol) afforded the corresponding esters. The synthesized complexes were characterized in detail by elemental analysis, ESI-MS, multinuclear ((1)H, (13)C, (15)N and (195)Pt) NMR spectroscopy and in two cases by X-ray crystallography. Cytotoxicity of novel platinum(IV) compounds was investigated in four human cancer cell lines (CH1, A549, SW480 and SK-OV-3). Remarkably, the most lipophilic complexes showed IC(50) values down to the low micromolar or even nanomolar range.     

Syntheses, electronic structures, and EPR/UV-vis-NIR spectroelectrochemistry of nickel(II), copper(II), and zinc(II) complexes with a tetradentate ligand based on S-methylisothiosemicarbazide

Template condensation of 3,5-di-tert-butyl-2-hydroxybenzaldehyde S-methylisothiosemicarbazone with pentane-2,4-dione and triethyl orthoformate at elevated temperatures resulted in metal complexes of the type M(II)L, where M = Ni and Cu and H(2)L = a novel tetradentate ligand. These complexes are relevant to the active site of the copper enzymes galactose oxidase and glyoxal oxidase. Demetalation of Ni(II)L with gaseous hydrogen chloride in chloroform afforded the metal-free ligand H(2)L. Then by the reaction of H(2)L with Zn(CH(3)COO)(2)·2H(2)O in a 1:1 molar ratio in 1:2 chloroform/methanol, the complex Zn(II)L(CH(3)OH) was prepared. The three metal complexes and the prepared ligand were characterized by spectroscopic methods (IR, UV-vis, and NMR spectroscopy), X-ray crystallography, and DFT calculations. Electrochemically generated one-electron oxidized metal complexes [NiL](+), [CuL](+), and [ZnL(CH(3)OH)](+) and the metal-free ligand cation radical [H(2)L](+?) were studied by EPR/UV-vis-NIR and DFT calculations. These studies demonstrated the interaction between the metal ion and the phenoxyl radical.     

Two Unusual Methylidenecyclopropane Glucosides from Metaxya rostrata C.Presl

Two new natural compounds, (1R,2E)‐2‐(6‐hydroxyhexylidene)cyclopropyl‐β‐D ‐glucopyranoside ( 1 ) and (6E)‐6‐[(2R)‐2‐(β‐D ‐glucopyranosyloxy)cyclopropylidene]hexanoic acid ( 2 ), glucosides of a very rare methylidenecyclopropane alcohol, as well as two known glycosides of phenolic acids, namely 4‐O‐β‐D ‐glucopyranosylcaffeic acid ( 3 ) and (E)‐4‐O‐β‐D ‐glucopyranosylcoumaric acid ( 4 ), and methyl α‐fructofuranoside ( 5 ) were isolated for the first time from the rhizomes of the tree fern Metaxya rostrata C.Presl . The structures were elucidated on the basis of detailed spectroscopic data analysis, and the structure of 1 was additionally confirmed by X‐ray crystal‐structure analysis.     

Kinetics of Enzymatic Hydrolysis of Olive Oil in Batch and Fed-batch Systems

This work reports experimental data, kinetic modeling, and simulations of enzyme-catalyzed hydrolysis of olive oil. This reaction was performed in batch system and an ordered-sequential Bi Bi model was used to model the kinetic mechanism. A fed-batch system was proposed and experimental data were obtained and compared to the simulated values. The kinetic model used was able to correlate the experimental data, in which a satisfactory agreement between the experimental data and modeling results was obtained under different enzyme concentration and initial free water content. Therefore, the modeling allowed a better understanding of the reaction kinetics and affords a fed-batch simulation for this system. From the results obtained, it was observed that the fed-batch approach showed to be more advantageous when compared to the conventional batch system.     

Maltol‐Derived Ruthenium–Cymene Complexes with Tumor Inhibiting Properties: The Impact of Ligand–Metal Bond Stability on Anticancer Activity In Vitro

Organometallic ruthenium–arene compounds bearing a maltol ligand have been shown to be nearly inactive in in vitro anticancer assays, presumably due to the formation of dimeric Ru^II species in aqueous solutions. In an attempt to stabilize such complexes, [Ru(η⁶‐p‐cymene)(XY)Cl] (XY=pyrones or thiopyrones) complexes with different substitution pattern of the (thio)pyrone ligands have been synthesized, their structures characterized spectroscopically, and their aquation behavior investigated as well as their tumor‐inhibiting potency. The aquation behavior of pyrone systems with electron‐donating substituents and of thiopyrone complexes was found to be significantly different from that of the maltol‐type complex reported previously. However, the formation of the dimer can be excluded as the primary reason for the inactivity of the complex because some of the stable compounds are not active in cancer cell lines either. In contrast, studies of their reactivity towards amino acids demonstrate different reactivities of the pyrone and thiopyrone complexes, and the higher stability of the latter probably renders them active against human tumor cells.     

En route to osmium analogues of KP1019: synthesis, structure, spectroscopic properties and antiproliferative activity of trans-[Os(IV)Cl4(Hazole)2

By controlled Anderson type rearrangement reactions complexes of the general formula trans-[Os(IV)Cl(4)(Hazole)(2)], where Hazole = 1H-pyrazole, 2H-indazole, 1H-imidazole, and 1H-benzimidazole, have been synthesized. Note that 2H-indazole tautomer stabilization in trans-[Os(IV)Cl(4)(2H-indazole)(2)] is unprecedented in coordination chemistry of indazole. The metal ion in these compounds possesses the same coordination environment as ruthenium(III) in (H(2)ind)[Ru(III)Cl(4)(Hind)(2)], where Hind = 1H-indazole, (KP1019), an investigational anticancer drug in phase I clinical trials. These osmium(IV) complexes are appropriate precursors for the synthesis of osmium(III) analogues of KP1019. In addition the formation of an adduct of trans-[Os(IV)Cl(4)(Hpz)(2)] with cucurbit[7]uril is described. The compounds have been comprehensively characterized by elemental analysis, EI and ESI mass spectrometry, spectroscopy (IR, UV-vis, 1D and 2D NMR), cyclic voltammetry, and X-ray crystallography. Their antiproliferative acitivity in the human cancer cell lines CH1 (ovarian carcinoma), A549 (nonsmall cell lung carcinoma), and SW480 (colon carcinoma) is reported.     

Conjugation of organoruthenium(II) 3-(1H-benzimidazol-2-yl)pyrazolo[3,4-b]pyridines and indolo[3,2-d]benzazepines to recombinant human serum albumin: a strategy to enhance cytotoxicity in cancer cells

Following our strategy of coupling cyclin-dependent kinase (Cdk) inhibitors with organometallic moieties to improve their physicochemical properties and bioavailability, five organoruthenium complexes (1c-5c) of the general formula [RuCl(η(6)-arene)(L)]Cl have been synthesized in which the arene is 4-formylphenoxyacetyl-η(6)-benzylamide and L is a Cdk inhibitor [3-(1H-benzimidazol-2-yl)-1H-pyrazolo[3,4-b]pyridines (L1-L3) and indolo[3,2-d]benzazepines (L4 and L5)]. All of the compounds were characterized by spectroscopic and analytical methods. Upon prolonged standing (2-3 months) at room temperature, the dimethyl sulfoxide (DMSO) solutions of 1c and 2c(-HCl) afforded residues, which after recrystallization from EtOH and EtOH/H(2)O, respectively, were shown by X-ray diffraction to be cis,cis-[Ru(II)Cl(2)(DMSO)(2)(L1)]·H(2)O and mer-[Ru(II)Cl(DMSO)(3)(L2-H)]·H(2)O. Compound 5c, with a coordinated amidine unit, undergoes E/Z isomerization in solution. The antiproliferative activities and effects on the cell cycle of the new compounds were evaluated. Complexes 1c-5c are moderately cytotoxic to cancer cells (CH1, SW480, A549, A2780, and A2780cisR cell lines). Therefore, in order to improve their antiproliferative effects, as well as their drug targeting and delivery to cancer cells, 1c-5c were conjugated to recombinant human serum albumin, potentially exploiting the so-called "enhanced permeability and retention" effect that results in the accumulation of macromolecules in tumors. Notably, a marked increase in cytotoxicity of the albumin conjugates was observed in all cases.     

Ni Oxidation State and Ligand Saturation Impact on the Capability of Octaazamacrocyclic Complexes to Bind and Reduce CO2

Two 15-membered octaazamacrocyclic nickel(II) complexes are investigated by theoretical methods to shed light on their affinity forwards binding and reducing CO₂. In the first complex ¹[Ni^IIL]⁰, the octaazamacrocyclic ligand is grossly unsaturated (π-conjugated), while in the second ¹[Ni^IILH]²⁺ one, the macrocycle is saturated with hydrogens. One and two-electron reductions are described using Mulliken population analysis, quantum theory of atoms in molecules, localized orbitals, and domain averaged fermi holes, including the characterization of the Ni-C_CO2 bond and the oxidation state of the central Ni atom. It was found that in the [NiLH] complex, the central atom is reduced to Ni⁰ and/or Ni^I and is thus able to bind CO₂ via a single σ bond. In addition, the two-electron reduced ³[NiL]²⁻ species also shows an affinity forwards CO₂.