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γ-Valerolactone (GVL) is a key downstream product of renewable biomass with enormous potential for the manufacture of advanced biofuels, bio-based chemicals, materials or for its direct use as an additive to gasoline and is obtained by the hydrogenation reaction of the important platform molecule levulinic acid (LA). Unprecedented high catalytic activities (TOF = 42530 h−1) have been achieved by water-dispersible ruthenium nanoparticles (RuNPs) stabilized by a broad spectrum of water-soluble polymers with both oxygen-containing functionalities such as the non-toxic and inexpensive polyethylene glycol (PEG) and poly(vinyl alcohol) (PVA) and with polymers bearing nitrogen-groups in the hydrogenation of LA to obtain with high selectivities (99.2 mol%) GVL in the aqueous medium. Furthermore, water provides for a desired higher dispersion of RuNPs catalysts capable to achieve high activities and impressive stabilities. The calculated apparent activation energy of the RuNPs/PEG catalyst amounts a low value of 32.3 kJ/mol. TEM investigations revealed the formation of RuNPs/PVA catalysts with a small average particle size diameter of 2.8 ± 0.1 nm which is consistent with the high catalytic activities. Recycling experiments have shown that the RuNPs/PVA catalyst demonstrated superb stability and selectivity in five consecutive runs at a high molar ratio LA/Ru = 16000 which is of industrial interest. © 2022 The Authors

The synthesis, DNA binding properties and cytotoxicity of a series of Ru(II)-arene complexes containing oligocationic ammonium-functionalized triarylphosphines, of the type Ru(p-cymene)Cl2(L) (L ¼ oligocationic phosphine), are reported. The complexes are highly charged (the overall charge states being þ3 and þ6) and circular dichroism spectroscopy and gel electrophoresis studies indicate that the compounds interact strongly with DNA via electrostatic interactions. Despite forming strong interactions with DNA, the complexes exhibit only modest cytotoxicities on the human ovarian cancer cell lines A2780 and A2780cisR.

A series of bioactive molecules were synthesized from the condensation of aspirin or chlorambucil with terminal alkynes bearing alcohol or amine substituents. Insertion of the resulting alkynes into the iron-carbyne bond of readily accessible diiron bis(cyclopentadienyl) mu-aminocarbyne complexes, [1a,b]CF3SO3, afforded novel diiron complexes with a bridging vinyliminium ligand, [2-10]CF3SO3, functionalized with a bioactive moiety. All compounds were characterized by elemental analysis and IR and multinuclear NMR spectroscopy and in three cases by single-crystal X-ray diffraction. Moreover, the D2O solubility, stability in D2O and cell culture media, and octanol-water partition coefficients of diiron complexes were determined spectroscopically. The cytotoxicity of the complexes was assessed in the tumorigenic A2780 and A2780cisR and the nontumorigenic HEK 293T cell lines. Some complexes exhibit high potency and the ability to overcome resistance in A2780cisR cells (aspirin complexes) or high selectivity relative to HEK 293T cells (chlorambucil complexes). Further studies indicate that the complexes significantly trigger intracellular ROS production, irrespective of the nature of the bioactive fragment. DNA alkylation and protein binding studies were also undertaken.

Four bipyridine-Type ligands variably derivatized with two bioactive groups (taken from ethacrynic acid, flurbiprofen, biotin, and benzylpenicillin) were prepared via sequential esterification steps from commercial 2,2′-bipyridine-4,4′-dicarboxylic acid and subsequently coordinated to ruthenium(II) p-cymene and iridium(III) pentamethylcyclopentadienyl scaffolds. The resulting complexes were isolated as nitrate salts in high yields and fully characterized by analytical and spectroscopic methods. NMR and MS studies in aqueous solution and in cell culture medium highlighted a substantial stability of ligand coordination and a slow release of the bioactive fragments in the latter case. The complexes were assessed for their antiproliferative activity on four cancer cell lines, showing cytotoxicity to the low micromolar level (equipotent with cisplatin). Additional biological experiments revealed a multimodal mechanism of action of the investigated compounds, involving DNA metalation and enzyme inhibition. Synergic effects provided by specific combinations of metal and bioactive fragments were identified, pointing toward an optimal ethacrynic acid/flurbiprofen combination for both Ru(II) and Ir(III) complexes.

Regio- and stereoselective nucleophilic attack of cyanide (from NBu4CN) to cationic diiron vinyliminium compounds [Fe2Cp2(CO)(mu-CO){mu-eta(1):eta(3)-C-(R')C(R '')-CNMe2}]CF3SO3 ([1a-f]CF3SO3) affords the nitrile-aminoallylidene derivatives 2a-f in good to excellent yield. The analogous reaction of [1g]CF3SO3, comprising two different N substituents, gives 4 (63%) as a mixture of two stereoisomers. The new products [lg]CF3SO3, 2a-f, and 4 were characterized by IR and NMR spectroscopy and in a number of cases by IR-spectroelectrochemistry and single-crystal X-ray diffraction. The allylidene complexes are air-stable and robust in aqueous solution; however, in general they undergo oxidation within a biologically relevant range of potentials. DFT calculations were carried out to rationalize the observed stereoselectivity of the synthesis reaction and other structural and thermodynamic aspects. The cytotoxicity of 2a-f was assessed on cisplatin-sensitive and -resistant human ovarian carcinoma (A2780 and A2780cisR) cell lines and human embryonic kidney (HEK-293) cells. Experiments reveal that treatment with the compounds leads to ROS production, with an absence of direct interactions with double-stranded DNA (calf thymus) and bovine serum albumin.

A series of diiron/tetrairon compounds containing a S- or a Se-function (2a&ndash, d, 4a&ndash, d, 5a&ndash, b, 6), and the monoiron [FeCp(CO){SeC1(NMe2)C2HC3(Me)}] (3) were prepared from the diiron &mu, vinyliminium precursors [Fe2Cp2(CO)( &mu, CO){ &mu, &eta, 1: &eta, 3-C3(R&rsquo, )C2HC1N(Me)(R)}]CF3SO3 (R = R&rsquo, = Me, 1a, R = 2,6-C6H3Me2 = Xyl, R&rsquo, = Ph, 1b, R = Xyl, R&rsquo, = CH2OH, 1c), via treatment with S8 or gray selenium. The new compounds were characterized by elemental analysis, IR and multinuclear NMR spectroscopy, and structural aspects were further elucidated by DFT calculations. The unprecedented metallacyclic structure of 3 was ascertained by single crystal X-ray diffraction. The air-stable compounds (3, 4a&ndash, b, 6) display fair to good stability in aqueous media, and thus were assessed for their cytotoxic activity towards A2780, A2780cisR, and HEK-293 cell lines. Cyclic voltammetry, ROS production and NADH oxidation studies were carried out on selected compounds to give insights into their mode of action.

A facile route to Pt-II complexes doubly functionalized with bioactive molecules through a bipyridine-type ligand is described. Initially, ligands L-EE (containing two ethacrynic acid units), L-EF (ethacrynic acid+flurbiprofen) and L-EB (ethacrynic acid+biotin) were obtained in moderate to good yields from 2,2 '-bipyridine-4,4 '-dicarboxylic acid. Subsequent reaction of the ligands with [PtCl2(DMSO)(2)] afforded complexes [PtCl2(L-EE)] (2), [PtCl2(L-EF)] (3) and [PtCl2(L-EB)] (4) in high yields. All compounds were fully characterized by analytical and spectroscopic methods. Complexes 2-4 are highly stable in water/DMSO solution at 37 degrees C after 72 h, whereas progressive release of the bioactive fragments was detected in a cell culture medium. The compounds were assessed for their in vitro antiproliferative activity towards tumorigenic A2780, A2780cisR and Y79 cells and non-tumourigenic HEK293 cells. In particular, the combination of ethacrynic acid and flurbiprofen in 3 overcomes cisplatin-based resistance and provides strong cancer cell selectivity. Enzyme inhibition assays on human GST P1 and human COX-2 and cross-experiments with complex 1, analogous to 2-4 but lacking bio-groups, revealed a clear synergy between the Pt-II frame and the bioactive organic components.

The reaction of pyrrolidine with a series of cationic diiron cyclopentadienyl complexes containing a bridging vinyliminium ligand gives access to piano stool monoiron complexes based on a five-membered metallacycle that includes a vinyl-aminoalkylidene moiety, in moderate to high yields. The resulting metallacyclic motif (aminoalkylidene-ferracyclopentenone) is unique in organometallic chemistry and is partially pre-constructed on the dinuclear frame. The monoiron products were fully characterized by elemental analysis, IR and multinuclear NMR spectroscopy, and in a number of cases by X-ray diffraction and cyclic voltammetry. They are robust in aqueous solutions and generally unreactive towards alkylating agents in organic solvents. However, a cationic derivative was prepared in high yield by methylation of a 2-pyridyl group. The cytotoxicity of both neutral and ionic complexes was assessed on cancerous (A2780 and A280cisR) and non-cancerous (HEK293) cell lines, revealing the influence of local structural modifications on the antiproliferative activity and the selectivity of the compounds.

PubMed ID: 9649620, Both Streptomyces lividans and Streptomyces avermitilis encode similar systems of post-replicative DNA modification which act site-specifically on closely opposed guanines on either strand. The modifications can be detected since they react in vitro with an oxidative derivative of Tris, resulting in strand cleavage. Previous analysis of the preferred modification site of plasmid pIJ101 indicated that extensive amounts of flanking sequence, including direct and inverted repeat structures, are required to direct modification in vivo within a central 6 bp palindrome. We have now examined the preferred modification sites of a chromosomal element, the 5.7 kb amplified DNA sequence (ADS5.7) found in certain S.lividans mutants. In contrast to the pIJ101 site, each of the ADS5.7 sites is intragenic and modified with a 10-fold reduced frequency. However, similar extents of flanking sequence are required for authentic double-strand modification; deletion mutants exhibited different modification profiles, including displaced double-stranded or single-stranded modification. Comparison of different modification sites reveals conservation of the central core sequence, but no significant similarities between flanking sequences. Enhanced modification was detected in a cloned region of the ADS5.7, suggesting that local DNA topology, probably influenced by both DNA supercoiling and the nature of flanking sequences, can influence the modifying activity.

Although ferrocene derivatives have attracted considerable attention as possible anticancer agents, the medicinal potential of diiron complexes has remained largely unexplored. Herein, we describe the straightforward multigram-scale synthesis and the antiproliferative activity of a series of diiron cyclopentadienyl complexes containing a bridging vinyliminium ligand. IC50 values in the low to mid-micromolar range were assessed against cisplatin sensitive and resistant human ovarian carcinoma (A2780 and A2780cisR) cell lines. Notable selectivity towards the cancerous cells lines compared to the non-tumoural human embryonic kidney (HEK-293) cell line was observed for selected compounds. The mode of action is attributed to a one electron reduction process, which results in a fragmentation releasing an activated mononuclear iron derivative. The large structural variability, amphiphilic character and good stability in aqueous media of the diiron vinyliminium complexes collectively provide favourable properties compared to other widely studied classes of iron-based anticancer candidates. .