Structural Properties, Cytotoxicity, and Anti-Inflammatory Activity of Silver(I) Complexes with tris(p-tolyl)Phosphine and 5-Chloro-2-Mercaptobenzothiazole

The synthesis and characterization of the silver(I) chloride complex of formula {[AgCI(CMBZT)(TPTP)2] · (MeOH)} (1) (CMBZT = 5-chloro-2-mercaptobenzothiazole, TPTP = tris(p-tolyl)phosphine) is described. Also the structure of the hydrate derivative {[AgCI(TPTP)3] · (0.5 · H2O)} (2) of the corresponding known anhydrous silver complex (Zartilas et al., 2009), and the polymorph 3 of the known [AgI(TPTP)3] complex (Zartilas et al., 2009) were determined and compared with the known ones. In addition, the structure of the known one silver(I) cluster {[AgI(TPTP)]4} (4) (Meijboom et al., 2009) was re-determined at 120(2) K and possible Ag-Ag interactions were analyzed. The compounds 1–4 were characterized by X-ray crystallography at r.t (1) and 120 K (2–4). All these complexes and {[(Et3NH)+]2 · [Ag6(μ3-Hmna)4(μ3-mna)2]2− · (DMSO)2 · (H2O)} (5) (Hmna = 2-mercaptonicotinic acid) were evaluated for cytotoxic and anti-inflammatory activity. The in vitro testing of cytotoxic activity of 1–5 against leiomyosarcoma cancer cells (LMS), were evaluated with Trypan Blue and Thiazolyl Blue Tetrazolium Bromide or 3-(4.5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide (MTT) assays. The flow cytometry assay for complex 1 and showed that at 15 μM of 1, 62.38% of LMS cells undergo apoptosis, while 7% of LMS cells undergo cell necrosis. The antitumor activity of 3 is comparable with that of its reported polymorph (Zartilas et al., 2009). The anti-inflammatory, activity of complexes 1–3 and 5 was also studied. The activity towards cell viability was 2 > 3 > 5 > 1 > 4, while the order of the inhibitory activity in cell growth proliferation follows the order, 2 > 3 > 1 > 4 > 5. The anti-inflammatory activity on the other hand is 1 > 2 > 5 > ⋯ >3

Synthesis, Characterization, and Biological Studies of Organotin(IV) Derivatives with o- or p-hydroxybenzoic Acids

Organotin(IV) complexes with o- or p-hydroxybenzoic acids (o-H2BZA or p-H2BZA) of formulae [R2Sn(HL)2] (where H2L = o-H2BZA and R = Me- (1), n-Bu- (2)); [R3Sn(HL)] (where H2L = o-H2BZA and R = n-Bu- (3), Ph- (4) or H2L = p-H2BZA and R = n-Bu- (5), Ph- (6)) were synthesized by reacting a methanolic solution of di- and triorganotin(IV) compounds with an aqueous solution of the ligand (o-H2BZA or p-H2BZA) containing equimolar amounts of potassium hydroxide. The complexes were characterized by elemental analysis, FT-IR, Far-IR, TGA-DTA, FT-Raman, Mössbauer spectroscopy, 1H, 119Sn-NMR, UV/Vis spectroscopy, and Mass spectroscopy. The X-ray crystal structures of complexes 1 and 2 have also been determined. Finally, the influence of these complexes 1–6 upon the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX) was kinetically studied and the results showed that triorganotin(IV) complex 6 has the lowest IC50 value. Also complexes 1–6 were studied for their in vitro cytotoxicity against sarcoma cancer cells (mesenchymal tissue) from the Wistar rat, and the results showed that the complexes have high activity against these cell lines with triphenyltin((IV) complex 4 to be the most active one

Synthesis, structural characterization and biological studies of novel mixed ligand Ag(I) complexes with tri-phenylphosphine and aspirin or salicylic acid

Two new mixed ligand silver(I) complexes of formulae {[Ag(tpp)3(asp)](dmf)} (1) (aspH = o-acetylsalicylic acid and tpp = triphenylphosphine) and [Ag(tpp)2(o-Hbza)] (2) (o-HbzaH = o-hydroxy-benzoic acid) were synthesized and characterized by elemental analyses, spectroscopic techniques and X-ray crystallography at ambient conditions. Three phosphorus and one carboxylic oxygen atoms from a de-protonated aspirin ligand in complex 1 and two phosphorus and two carboxylic oxygen atoms from a chelating o-Hbza anion in complex 2 form a tetrahedral geometry around Ag(I) ions in both complexes. Complexes 1 and 2 and the silver(I) nitrate, tpp, aspNa and o-HbzaH were tested for their in vitro cytotoxic activity against leiomyosarcoma cells (LMS), human breast adenocarcinoma cells (MCF-7) and normal human fetal lung fibroblasts (MRC-5) cells with Thiazolyl Blue Tetrazolium Bromide (MTT) assay. For both cell lines 1 and 2 were found to be more active than cisplatin. Additionally, 1 and 2 exhibit lower activity on cell growth proliferation of MRC-5 cells. The type of LMS cell death caused by 1 and 2 were evaluated in vitro by use of flow cytometry assay. The results show that at concentrations of 1.5 and 1.9 lV of complex 1, 44.1% and 69.4%, respectively of LMS cells undergo programmed cell death (apoptosis). When LMS cells were treated with 1.6 and 2.3 lM of 2, LMS cells death was by 29.6% and 81.3%, respectively apoptotic. Finally, the influence of the complexes 1 and 2, upon the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX) was kinetically and theoretically studied. The binding of 1 and 2 towards LOX was also investigated by Saturation Transfer Difference (STD) 1 H NMR experiment

Cognitive Profile of Students Who Enter Higher Education with an Indication of Dyslexia

For languages other than English there is a lack of empirical evidence about the cognitive profile of students entering higher education with a diagnosis of dyslexia. To obtain such evidence, we compared a group of 100 Dutch-speaking students diagnosed with dyslexia with a control group of 100 students without learning disabilities. Our study showed selective deficits in reading and writing (effect sizes for accuracy between d = 1 and d = 2), arithmetic (d≈1), and phonological processing (d>0.7). Except for spelling, these deficits were larger for speed related measures than for accuracy related measures. Students with dyslexia also performed slightly inferior on the KAIT tests of crystallized intelligence, due to the retrieval of verbal information from long-term memory. No significant differences were observed in the KAIT tests of fluid intelligence. The profile we obtained agrees with a recent meta-analysis of English findings suggesting that it generalizes to all alphabetic languages. Implications for special arrangements for students with dyslexia in higher education are outlined

Mitigating risk of exceeding environmental limits requires ambitious food system interventions

Transforming the global food system is necessary to avoid exceeding planetary boundaries. A robust evidence base is crucial to assess the scale and combination of interventions required for a sustainable transformation. We developed a risk assessment framework, underpinned by a meta-regression of 60 global food system modeling studies, to quantify the potential of individual and combined interventions to mitigate the risk of exceeding the boundaries for land-system change, freshwater use, climate change, and biogeochemical flows by 2050. Limiting the risk of exceedance across four key planetary boundaries requires a high but plausible level of ambition in all demand-side (diet, population, waste) and most supply-side interventions. Attaining the required level of ambition for all interventions relies on embracing synergistic actions across the food system

How can diverse national food and land-use priorities be reconciled with global sustainability targets? Lessons from the FABLE initiative

There is an urgent need for countries to transition their national food and land-use systems toward food and nutritional security, climate stability, and environmental integrity. How can countries satisfy their demands while jointly delivering the required transformative change to achieve global sustainability targets? Here, we present a collaborative approach developed with the FABLE—Food, Agriculture, Biodiversity, Land, and Energy—Consortium to reconcile both global and national elements for developing national food and land-use system pathways. This approach includes three key features: (1) global targets, (2) country-driven multi-objective pathways, and (3) multiple iterations of pathway refinement informed by both national and international impacts. This approach strengthens policy coherence and highlights where greater national and international ambition is needed to achieve global goals (e.g., the SDGs). We discuss how this could be used to support future climate and biodiversity negotiations and what further developments would be needed

Synthesis, characterization and biological evaluation of novel antimony(III) iodide complexes with tetramethylthiourea and N-ethylthiourea

Novel trivalent antimony(III) complexes with tetramethylthiourea (TMTU) and N-ethylthiourea (NETU) were synthesized by the reaction of antimony(III) iodide (SbI3). Antimony(III) iodide complexes of formulae {[SbI2(µ2-I)(TMTU)2]2} (1) and {[(NETU)SbI2(µ2-I)2(µ2-S-NETU)SbI2(NETU)]} (2) were characterized by spectroscopic techniques (FT-IR, FT-Raman, 1H and 13C NMR), TG-DTA analysis and X-ray diffraction (XRD) analysis. Single-crystal X-ray diffraction studies showed that the complexes existed as doubly bridged (1) and triply bridged (2) dimers. Crystal structure of the ligand N-ethylthiourea was also determined with single crystal X-ray diffraction analysis. Complexes 1 and 2 were evaluated for their in vitro cytotoxic activity against human adenocarcinoma cells HeLa (cervix). The toxicity of 1 and 2 was evaluated on normal human fetal lung fibroblast cells (MRC-5). Both complexes showed selectivity against the cancerous, than normal cells. The influence of 1 and 2, on the catalytic peroxidation of the linoleic acid by the enzyme lipoxygenase (LOX) was determined experimentally and theoretically. The complexes 1 and 2 exhibited higher activity than free ligands against LOX. The in vitro antibacterial activities of free ligands and their antimony(III) iodide complexes 1 and 2 were tested against two Gram-negative (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853) and two Gram-positive (Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29212) bacteria. The complexes 1 and 2 were much more effective in terms of antimicrobial activity compared to the free ligands. © 2019 Elsevier B.V.I.I.O. acknowledges the financial support from Tekirdag Namik Kemal University Scientific Research Project (Project No. NKUBAP.01.GA.16.014)

Synthesis, characterization and cytotoxic properties of bismuth(III) chloride complexes with heterocyclic thioamides

Bismuth(III) complexes of the formulae [BiCl3(MBZT)(2)] center dot H2O} (1), {[BiCl2(mu(2)-Cl)(MMI)(2)](2)center dot(CH3)(2)CO} (2), {[BiCl3(mu(2)-S-PYT)(PYT)](2)} (3) {([BiCl2(MBZIM)(4)](+))center dot 2(Cl-) center dot(H3O+)center dot 2H(2)O} (4) and [BiCl3(tHPMT)(3)] (5) (where MBZT: 2-mercaptobenzothiazole, MMI: 2-mercapto-1-methylimidazole, PYT: 2-mercaptopyridine, MBZIM: 2-mercaptobenzimidazole, tHPMT: 2-mercapto-3,4,5,6-tetrahydro-pyrimidine) are reported. The compounds were characterized by spectroscopic techniques including FT-IR, FT-Raman, UV-Vis, H-1-, C-13-NMR spectroscopies, TG-DTA, e. a, molar conductivity and by single-crystal X-ray diffraction analysis. While 1, 4 and 5 are mononuclear compounds, 2 and 3 are dinuclear complexes in which the two Bi3+ ions are bridged through Cl- and SR groups respectively. Interestingly, 3 is the first example of dinuclear Bi3+ complex containing two Bi-(mu-SR)-Bi bridges between the two metal centers formed by covalent bonds. Compounds 1-5 were evaluated for their in vitro cytotoxic activity against human adenocarcinoma cervix (HeLa) and breast (MCF-7) cells. The toxicity of 1-5 was evaluated on normal human fetal lung fibroblast cells (MRC-5). The influence of 1-5, on the catalytic peroxidation of the linoleic acid by the enzyme lipoxygenase (LOX) was determined experimentally. (C) 2017 Elsevier B.V. All rights reserved.Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [114Z457]; Oncology Department of Novartis Hellas S.A.C.I [81939]This research was carried out in partial fulfillment of the requirements for the master thesis of S.Y. under the supervision of I.I.O. I.I.O. and S.Y. acknowledge the financial support from The Scientific and Technological Research Council of Turkey (TUBITAK, Project No. 114Z457). The Unit of Bioactivity Testing of Xenobiotics, of the University of Ioannina-Greece, is also acknowledged for providing access to the facilities. CNB and SKH acknowledge the Oncology Department of Novartis Hellas S.A.C.I. for the financial support to CNB (project number: 81939)