Search

Highlights: [•] The behavior of three pilot-scale sludge digesters was evaluated through modeling. [•] The ADM1 was able to predict the effects of thermal pretreatment and HRT changes. [•] Increases in the disintegration coefficient due to pretreatment were observed. [•] Model under/overestimation lower than 15% regarding CH4 production. [•] The ADM1 showed to be accurate and useful to predict the studied conditions. [Copyright &y& Elsevier]

We report the design, synthesis and biological studies on a group of mixed ligand Fe(III) complexes as anti-cancer drug candidates, namely their interaction with DNA, cytotoxicity and mechanism(s) of action. The aim is to obtain stable, efficient and selective Fe-complexes to be used as anti-cancer agents with less damaging side effects than previously reported compounds. Five ternary Fe(III) complexes bearing a tripodal aminophenolate ligand L2−, H 2 L = N , N -bis(2-hydroxy-3,5-dimethylbenzyl)- N -(2-pyridylmethyl)amine, and different aromatic bases NN = 2,2′-bipyridine [Fe(L)(bipy)]PF 6 (1), 1,10-phenanthroline [Fe(L)(phen)]PF 6 (2), or a phenanthroline derivative co-ligand: [Fe(L)(amphen)]NO 3 (3), [Fe(L)(amphen)]PF 6 (3a), [Fe(L)(Clphen)]PF 6 (4), [Fe(L)(epoxyphen)]PF 6 (5) (where amphen = 1,10-phenanthroline-5-amine, epoxyphen = 5,6-epoxy-5,6-dihydro-1,10-phenanthroline, Clphen = 5-chloro-1,10-phenanthroline) and the [Fe(L)(EtOH)]NO 3 (6) complex are synthesized. The compounds are characterized in the solid state and in solution by elemental analysis, ESI-MS, magnetic susceptibility measurements and FTIR, UV–Vis, 1H and 13C NMR and fluorescence spectroscopies. [Fe(phen)Cl 3 ] and [Fe(amphen)Cl 3 ] were also prepared for comparison purposes. Spectroscopic binding studies indicate groove binding as the main interaction for most complexes with DNA, and for those containing amphen a B- to Z-DNA conformational change is proposed to occur. As determined via MTT analysis all compounds 1 – 6 are cytotoxic against a panel of three different cell lines (HeLa, H1299, MDA-MB-231). For selected compounds with promising cytotoxic activity, apoptosis was evaluated using cell and DNA morphology, TUNEL, Annexin V/7AAD staining and caspase3/7 activity. The compounds induce oxidative DNA damage on plasmid DNA and in cell culture as assessed by 8-oxo-Guanine and γH2AX staining. Comet assay confirmed the presence of genomic damage. There is also increased reactive oxygen species formation following drug treatment, which may be the relevant mechanism of action, thus differing from that normally assumed for cisplatin. The Fe(III)-complexes were also tested against strains of M. Tuberculosis (MTb), complex 2 depicting higher anti -MTb activity than several known second line drugs. Hence, these initial studies show prospective anti-cancer and anti-MTb activity granting promise for further studies. Image 1 • Novel Fe(III)-aminophenolate-phenanthroline complexes were obtained. • These new Fe(III)-complexes are cytotoxic against several cancer cells. • The Fe(III)-complexes trigger ROS accumulation and DNA damage. • The mode of cell death is apoptosis via caspase activation. [ABSTRACT FROM AUTHOR]

Several new coordinatively unsaturated iron(II) complexes of the types [Fe(SN R - Ph)X 2 ] (X = Cl, Br; R = H, Me, Et) and the dimeric complex [Fe(SN H –Ph)(μ-Cl)Cl] 2 containing bidentate N -(2-pyridyl)amino-diphenylphosphine sulfides were prepared and characterized by various methods including X-ray crystallography, 57 Fe Mössbauer spectroscopy, SQUID magnetometry, ESI-MS and DFT calculations. All complexes exhibit magnetic moments very close to 4.9 μ B reflecting the four unpaired d-electrons. In solution, as revealed by ESI MS studies, all compounds appear to be labile and complexes [Fe(SN R - Ph)X 2 ] seem to be in equilibrium with solvated FeX 2 , free ligand, and the five-coordinate cationic complexes [Fe(SN R - Ph) 2 X] + . The latter are the most prominent species in the ESI mass spectra. Despite their relatively low formal electron count all iron complexes were inert towards the addition of carbon monoxide. [ABSTRACT FROM AUTHOR]

Abstract: Reaction of [MnIII(acac)3] and [VIVO(acac)2] with the 1,4-diazabutadiene (DAB) ligands Ph–DAB–(CH2)3R [R=Si(OEt)3(1a); H (1b)] (L) leads to complexes of the type [MnII(acac)2L] and [VIVO(acac)L]Cl in good yields. These complexes were characterised by spectroscopic techniques, and magnetic measurements showed that in the case of the manganese the metal was reduced during the reaction with the nitrogen ligand. The oxovanadium and manganese complexes bearing the ligand with triethoxysilyl groups Ph–DAB–(CH2)3Si(OEt)3(1a) were immobilised in ordered MCM-41 by carrying out a grafting reaction. Tethered complexes of the same type were prepared by treating MCM-41 first with a toluene solution of 1a under reflux; manganese(III) and oxovanadium(IV) precursors were then introduced into the MCM-41-ligand by pore volume impregnation of complex solutions. The modified materials were characterised by powder X-ray diffraction, solid-state NMR (13C, 29Si), FTIR, thermogravimetric studies and low temperature nitrogen adsorption isotherms. The grafted materials contained 0.7wt% Mn and 0.8wt% V, while higher metal loadings were achieved when the materials were prepared by tethering (2.9wt% Mn and 2.4wt% V). The modified materials are active catalysts for the oxidation of cis-cyclooctene using tert-butylhydroperoxide as oxygen donor, at 328K, yielding 1,2-epoxycyclooctane as the main reaction product and 1,2-cyclooctanediol as a by-product. The vanadium-containing materials are more efficient epoxidation catalysts than the manganese ones. The catalytic behaviour of the heterogenised catalysts was also compared with that observed in homogeneous phase for the complexes [Mn(acac)2L] and [VO(acac)L]Cl. The vanadium catalysts exhibited the highest catalytic activity, whereas the manganese catalysts were the least active and selective to epoxide formation. [Copyright &y& Elsevier]