β-diketonate versus β-ketoiminate:the importance of a ferrocenyl moiety on improving the anticancer potency

Herein we present a library of fully characterized beta-diketonate and beta-ketoiminate compounds that are functionalized with a ferrocenyl moiety. Their cytotoxic potential has been determined by screening against human breast adenocarcinomas (MCF-7 and MDA-MB-231), human colorectal carcinoma p53 wild type (HCT116 p53(+/+)) and normal human prostate (PNT2) cell lines. The ferrocenyl beta-diketonate compounds are more than 18 times more cytotoxic than the ferrocenyl beta-ketoiminate analogues. Against MCF-7, compounds functionalized at the meta position are up to nine times more cytotoxic than when functionalized at the para position. The ferrocenyl beta-diketonate compounds have increased selectivity towards MCF-7 and MDA-MB-231, with several complexes having selectivity index (SI) values that are more than nine times (MCF-7) and more than six times (MDA-MB-231) that of carboplatin. The stability of these compounds in dimethyl sulfoxide (DMSO) and dimethylformamide (DMF) has been assessed by NMR spectroscopy and mass spectrometry studies, and the compounds show no oxidation of the iron center from Fe-II to Fe-III. Cytotoxicity screening was performed in both DMSO and DMF, with no significant differences observedin their potency

Cytotoxic Hydrogen Bridged Ruthenium Quinaldamide Complexes Showing Induced Cancer Cell Death by Apoptosis

This report presents the first known p-cymene ruthenium quinaldamide complexes which are stablized by a hydrogenbridging atom, [[{(p-cym)RuIIX(N,N)}{H+ }{(N,N)XRuII(p-cym)}][PF6] (N,N = functionalised quinaldamide and X = Cl or Br). These complexes are formed by a reaction of [p-cymRu(-X)2]2 with a functionalised quinaldamide ligand. When filtered over NH4PF6, and under aerobic conditions the equilibrium of NH4PF6 NH3 + HPF6 enables incorporation of HPF6 and the stabilisation of two monomeric ruthenium complexes by a bridging H+ , which are counter-balanced by a PF6 counterion. Xray crystallographic analysis is presented for six new structures with O···O distances of 2.430(3)-2.444(17) Å, which is significant for strong hydrogen bonds. Chemosensitivity studies against HCT116, A2780 and cisplatin-resistant A2780cis human cancer cells showed the ruthenium complexes with a bromide ancillary ligand to be more potent than those with a chloride ligand. The 4'-fluoro compounds show a reduction in potency for both chloride and bromide complexes against all cell lines, but an increase in selectivity towards cancer cells compared to non-cancer ARPE-19 cells, with a selectivity index > 1. Mechanistic studies showed a clear correlation between IC50 values and induction of cell death by apoptosis

Promoter-Wide Hypermethylation of the Ribosomal RNA Gene Promoter in the Suicide Brain

BACKGROUND: Alterations in gene expression in the suicide brain have been reported and for several genes DNA methylation as an epigenetic regulator is thought to play a role. rRNA genes, that encode ribosomal RNA, are the backbone of the protein synthesis machinery and levels of rRNA gene promoter methylation determine rRNA transcription. METHODOLOGY/PRINCIPAL FINDINGS: We test here by sodium bisulfite mapping of the rRNA promoter and quantitative real-time PCR of rRNA expression the hypothesis that epigenetic differences in critical loci in the brain are involved in the pathophysiology of suicide. Suicide subjects in this study were selected for a history of early childhood neglect/abuse, which is associated with decreased hippocampal volume and cognitive impairments. rRNA was significantly hypermethylated throughout the promoter and 5' regulatory region in the brain of suicide subjects, consistent with reduced rRNA expression in the hippocampus. This difference in rRNA methylation was not evident in the cerebellum and occurred in the absence of genome-wide changes in methylation, as assessed by nearest neighbor. CONCLUSIONS/SIGNIFICANCE: This is the first study to show aberrant regulation of the protein synthesis machinery in the suicide brain. The data implicate the epigenetic modulation of rRNA in the pathophysiology of suicide

Rhodium(III) dihalido complexes: The effect of ligand substitution and halido coordination on increasing cancer cell potency

This work presents the synthesis of eight new rhodium(III) dihalido complexes, [RhX2(L)(LH)] (where X = Cl or I), which incorporate two bidentate N-(3-halidophenyl)picolinamide ligands. The ligands have different binding modes in the complexes, whereby one is neutral and bound via N,N (LH) coordination, while the other is anionic and bound via N,O (L) coordination. The solid state and solution studies confirm multiple isomers are present when X = Cl; however, after a halide exchange with potassium iodide (X = I) the complexes exist exclusively as single stable trans isomers. NMR studies reveal the Rh(III) trans diiodido complexes remain stable in aqueous solution with no ligand exchange reported over 96 h. Chemosensitivity data against a range of cancer cell lines show two cytotoxic complexes, where L = N-(3-bromophenyl)picolinamide ligand. The results have been compared to the analogous Ru(III) complexes and overall highlight the Rh(III) trans diiodido complex to be ∼78× more cytotoxic than the analogous Rh(III) dichlorido complex, unlike the Ru(III) complexes which are equitoxic against all cell lines. Additionally, the Rh(III) trans diiodido complex is more selective toward cancerous cells, with selectivity index (SI) values >25-fold higher than cisplatin against colorectal carcinoma

Data to support study of Heteroleptic Iron(II) Complexes of Chiral 2,6-Bis(oxazolin-2-yl)-pyridine (PyBox) and 2,6-Bis(thiazolin-2-yl)pyridine Ligands ‒ the Interplay of Two Different Ligands on the Metal Ion Spin State

The spin-crossover properties of [Fe(LR)L][ClO4]2 (LR = a chiral PyBox {L1R} or ThioPyBox {L2R} derivative) show subtle differences depending on the tridentate ‘L’ co-ligand

Data to support study of The Spin States of Diastereomeric Iron(II)/Bis[2,6-Di(thiazolin-2-yl)-pyridine] (ThioPyBox) Complexes, and a Comparison with the Corresponding PyBox Derivatives

Diastereomeric [Fe(L1R)2][ClO4]2 (R = Ph, iPr) iron(II)/ThioPyBox derivatives show a larger discrimination of their spin states than the corresponding [Fe(L2R)2][ClO4]2 PyBox complexe

MINERvA neutrino detector response measured with test beam data

The MINERvA collaboration operated a scaled-down replica of the solid scintillator tracking and sampling calorimeter regions of the MINERvA detector in a hadron test beam at the Fermilab Test Beam Facility. This article reports measurements with samples of protons, pions, and electrons from 0.35 to 2.0 GeV/c momentum. The calorimetric response to protons, pions, and electrons are obtained from these data. A measurement of the parameter in Birks' law and an estimate of the tracking efficiency are extracted from the proton sample. Overall the data are well described by a Geant4-based Monte Carlo simulation of the detector and particle interactions with agreements better than 4%, though some features of the data are not precisely modeled. These measurements are used to tune the MINERvA detector simulation and evaluate systematic uncertainties in support of the MINERvA neutrino cross section measurement program.Comment: as accepted by NIM

First evidence of coherent K+K^{+} meson production in neutrino-nucleus scattering

Neutrino-induced charged-current coherent kaon production, $\nu_{\mu}A\rightarrow\mu^{-}K^{+}A$, is a rare, inelastic electroweak process that brings a $K^+$ on shell and leaves the target nucleus intact in its ground state. This process is significantly lower in rate than neutrino-induced charged-current coherent pion production, because of Cabibbo suppression and a kinematic suppression due to the larger kaon mass. We search for such events in the scintillator tracker of MINERvA by observing the final state $K^+$, $\mu^-$ and no other detector activity, and by using the kinematics of the final state particles to reconstruct the small momentum transfer to the nucleus, which is a model-independent characteristic of coherent scattering. We find the first experimental evidence for the process at $3\sigma$ significance.Comment: added ancillary file with information about the six kaon candidate