Reactivity of Cyanide and Thiocyanate Towards the Nitrosyl Carbonyl [Co(CO)3(NO)]

The reaction of equimolar amounts of [Co(CO)3(NO)] and [PPN]CN, PPN+ = (PPh3)2N+, in THF at room temperature resulted in ligand substitution of a carbonyl towards the cyanido ligand presumably affording the complex salt PPN[Co(CO)2(NO)(CN)] as a reactive intermediate species which could not be isolated. Applying the synthetic protocol using the nitrosyl carbonyl in excess, the title reaction afforded unexpectedly the novel complex salt PPN[Co2(μ‐CN)(CO)4(NO)2] (1) in high yield. Because of many disorder phenomena in crystals of 1 the corresponding NBu4+ salt of 1 has been prepared and the molecular structure of the dinuclear metal core in NnBu4[Co2(μ‐CN)(CO)4(NO)2] (2) was determined by X‐ray crystal diffraction in a more satisfactory manner. In contrast to the former result, the reaction of [PPN]SCN with [Co(CO)3(NO)] yielded the mononuclear complex salt PPN[Co(CO)2(NO)(SCN‐κN)] (3) in good yield whose molecular structure in the solid was even determined and its composition additionally confirmed by spectroscopic means

Metal and Substituent Influence on the Cytostatic Activity of Cationic Bis‐cyclometallated Iridium and Rhodium Complexes with Substituted 1,10‐Phenanthrolines as Ancillary Ligands

Synthesis and characterization of the new cyclometalated complex salts [Rh(ptpy)2(5.6‐dimethyl‐1,10‐phenanthroline)]PF6 (1a) [Rh(ptpy)2(2.9‐dimethyl‐4.7‐diphenyl‐1,10‐ phenanthroline)]PF6 (2a), [Rh(ptpy)2(5‐amino‐1,10‐phenanthroline)] PF6 (3a), and [M(ptpy)2 (pyrazino‐[2.3‐f]‐1,10‐phenanthroline)]PF6 (M = Rh, 4a; M = Ir, 4b), (ptpy = 2‐(p‐tolyl)pyridinato) are described. The molecular structures of compounds 1b and 4a in the solid state were determined by single‐crystal X‐ray diffraction. All these compounds and their already known Iridium counterparts 1b – 3b display significant cytotoxicity against human cancer cell lines MCF‐7 (human breast adenocarcinoma) and HT‐29 (colon adenocarcinoma) with IC50 values in the low micromolar range

Host Adaptation Through Hybridization: Genome Analysis of Triticale Powdery Mildew Reveals Unique Combination of Lineage-Specific Effectors

The emergence of new fungal pathogens through hybridization represents a serious challenge for agriculture. Hybridization between the wheat mildew (Blumeria graminis f. sp. tritici) and rye mildew (B. graminis f. sp. secalis) pathogens has led to the emergence of a new mildew form (B. graminis f. sp. triticale) growing on triticale, a man-made amphiploid crop derived from crossing rye and wheat, which was originally resistant to the powdery mildew disease. The identification of the genetic basis of host adaptation in triticale mildew has been hampered by the lack of a reference genome. Here, we report the 141.4-Mb reference assembly of triticale mildew isolate THUN-12 derived from long-read sequencing and genetic map-based scaffolding. All 11 triticale mildew chromosomes were assembled from telomere-to-telomere and revealed that 19.7% of the hybrid genome was inherited from the rye mildew parental lineage. We identified lineage-specific regions in the hybrid, inherited from the rye or wheat mildew parental lineages, that harbor numerous bona fide candidate effectors. We propose that the combination of lineage-specific effectors in the hybrid genome is crucial for host adaptation, allowing the fungus to simultaneously circumvent the immune systems contributed by wheat and rye in the triticale crop. In line with this, we demonstrate the functional transfer of the SvrPm3 effector from wheat to triticale mildew, a virulence effector that specifically suppresses resistance of the wheat Pm3 allelic series. This transfer is the likely underlying cause for the observed poor effectiveness of several Pm3 alleles against triticale mildew and exemplifies the negative implications of pathogen hybridizations on resistance breeding. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license

Cytotoxic Activities of Half‐sandwich M(III) Complexes (M=Rh, Ir) Bearing Chloro‐substituted Bidentate‐coordinated Phenanthroline or Terpyridine Ligands

The synthesis and characterization of four compounds [M(η5-C5Me5)(N^N)Cl]PF6 [N^N=4,7-dichloro-1,10-phenanthroline with M=Rh, 1, and M=Ir, 2, and N^N=4'-(4-chlorophenyl)-2,2':6',2''-terpyridine in the κ2N,N'-coordination mode with M=Rh, 3, and M=Ir, 4] are described. All compounds were characterized by spectroscopic means and their molecular structures in the crystal were confirmed by single-crystal X-ray diffraction studies. The cytotoxicity of all compounds was evaluated by MTT assay against the three cancer cell lines HeLa (cervical carcinoma), HT-29 (colon adenocarcinoma) and MCF-7 (human breast adenocarcinoma). The complexes 3 and 4 display promising activity with IC50 values of 1 μM. The rhodium(III) complex 1 also shows highly improved cytotoxicity compared to cisplatin against the cancer cell lines HT-29 and MCF-7. In contrast to this, the iridium(III) complex 2 is even less active against the HeLa cell line than cisplatin

Cytotoxic Activity of Some Half‐sandwich Rhodium(III) Complexes Containing 4,4’‐disubstituted‐2,2’‐bipyridine Ligands

The synthesis and characterization of three compounds [Rh(η5-C5Me5)Cl(N^N)]PF6 (N^N=4,4’-disubstituted-2,2’-bipyridines, 1–3) are described. The cationic complexes contain the bidentate ligands N^N=4,4'-di-tert-butyl-2,2'-bipyridine (1), N^N=4,4'-dinonyl-2,2'-bipyridine (2) and N^N=4,4'-diamino-2,2'-bipyridine (3). The complex salts were obtained by the bridge-splitting reaction from the precursor [{Rh(η5-C5Me5)(μ-Cl)Cl}2] and subsequent salt metathesis affording their corresponding hexafluorido phosphate salts. All compounds were characterized by elemental analysis and spectroscopic means. Additionally, the molecular structure of compound 3 in the solid was determined by a single-crystal X-ray diffraction study. The cytotoxicity of all three compounds was examined by MTT assay against two cancer cell lines – HT-29 (colon adenocarcinoma) and MCF-7 (human breast adenocarcinoma) - and normal human fibroblast cells (GM5657T). Compound 1 has moderate cytotoxicity against both cell lines, while compound 2 is seven to nine times more cytotoxic than cisplatin against MCF-7 and HT-29, respectively. In contrast to cisplatin, both compounds are more active against cancer cells than fibroblasts, thus showing some cancer selectivity

Cytotoxic Activities of Bis-cyclometalated M(III) Complexes (M=Rh, Ir) Containing 5-substituted 1,10-Phenanthroline or 4,4'-substituted 2,2'-Bipyridine Ligands

The synthesis and characterization of eight new bis-cyclometalated compounds [M(ptpy)(2)(NN)]PF6 (ptpy=2-(p-tolyl)pyridinato;NN=5-chloro-1,10-phenanthroline: M=Rh, 1;M=Ir, 2);NN=5-methyl-1,10-phenanthroline: M=Rh, 3;M=Ir, 4;NN=4,4'-diphenyl-2,2'-bipyridine: M=Rh, 5;M=Ir, 6;NN=4,4'-diamino-2,2'-bipyridine: M=Rh, 7;M=Ir, 8) are described. All compounds were characterized by spectroscopic means. Additionally, the molecular structures of compounds 4, 5, 6, and 8 in the crystal were determined by single-crystal X-ray diffraction studies. To explore the cytotoxic properties of all new eight compounds, colorimetric assays (MTT assay) against prominent cancer cell lines, MCF-7 and HT-29, were performed. The determined IC50 values are in the low micromolar range, between 1.3-5.6 mu M. The most effective compounds are 1 and 2 with 5-chloro-substituted phenanthroline ligands, whereas the diamino-substituted bipyridine ligands (5 and 6) are the least cytotoxic compounds. The tested complexes showed a significant increase in cytotoxicity, up to 25-fold increase in MCF-7 cancer cells, and up to 60-fold increase in the HT-29 cell line compared to the established anticancer compound cisplatin under identical conditions

The broad use of the Pm8 resistance gene in wheat resulted in hypermutation of the AvrPm8 gene in the powdery mildew pathogen

Background: Worldwide wheat production is under constant threat by fast-evolving fungal pathogens. In the last decades, wheat breeding for disease resistance heavily relied on the introgression of chromosomal segments from related species as genetic sources of new resistance. The Pm8 resistance gene against the powdery mildew disease has been introgressed from rye into wheat as part of a large 1BL.1RS chromosomal translocation encompassing multiple disease resistance genes and yield components. Due to its high agronomic value, this translocation has seen continuous global use since the 1960s on large growth areas, even after Pm8 resistance was overcome by the powdery mildew pathogen. The long-term use of Pm8 at a global scale provided the unique opportunity to study the consequences of such extensive resistance gene application on pathogen evolution. Results: Using genome-wide association studies in a population of wheat mildew isolates, we identified the avirulence effector AvrPm8 specifically recognized by Pm8. Haplovariant mining in a global mildew population covering all major wheat growing areas of the world revealed 17 virulent haplotypes of the AvrPm8 gene that grouped into two functional categories. The first one comprised amino acid polymorphisms at a single position along the AvrPm8 protein, which we confirmed to be crucial for the recognition by Pm8. The second category consisted of numerous destructive mutations to the AvrPm8 open reading frame such as disruptions of the start codon, gene truncations, gene deletions, and interference with mRNA splicing. With the exception of a single, likely ancient, gain-of-virulence mutation found in mildew isolates around the world, all AvrPm8 virulence haplotypes were found in geographically restricted regions, indicating that they occurred recently as a consequence of the frequent Pm8 use. Conclusions: In this study, we show that the broad and prolonged use of the Pm8 gene in wheat production worldwide resulted in a multitude of gain-of-virulence mechanisms affecting the AvrPm8 gene in the wheat powdery mildew pathogen. Based on our findings, we conclude that both standing genetic variation as well as locally occurring new mutations contributed to the global breakdown of the Pm8 resistance gene introgression

Cytotoxic Activities of Bis-cyclometalated Iridium(III) Complexes Containing Chloro-substituted kappa N-2-terpyridines

The synthesis and characterization of two new bis-cyclometalated compounds [Ir(ptpy)(2)(kappa N-2-terpy-C6H4Cl-p)]PF6 [terpy-C6H4Cl-p=4'-(4-chlorophenyl)-2,2':6',2''-terpyridine, (1)], and [Ir(ptpy)(2)(kappa N-2-terpy-Cl)]PF6 [terpy-Cl=4'-chloro-2,2':6',2''-terpyridine, (2);ptpy=2-(p-tolyl)pyridinato)] are described. The molecular structures of compounds 1 and 2 in the crystal were determined by single-crystal X-ray diffraction. 1 crystallized from dichloromethane/methanol/iso-hexane in the monoclinic space group P2/(n) and 2 from the same mixture of solvents in the triclinic space group P(-)1. Photophysical investigations on 1 and 2 revealed broad unstructured luminescence in the red spectral region with the emission maxima in dichloromethane at 620 and 630 nm respectively. To explore cytotoxic properties of compounds 1 and 2, a colorimetric assay (MTT assay) against prominent cancer cell lines, MCF-7 and HT-29, was performed. The determined IC50 values are in the low micromolar range (2-3 mu M). In comparison to cisplatin, the tested complexes 1 and 2 exhibit up to >20-fold (MCF-7) and >40-fold (HT-29) increase in biological activity

Bis‐cyclometalated Rhodium and Iridium Chloride Complexes Yield Different Products Upon Reaction With 9,10‐Diaminophenanthrene

The reaction of 9.10‐diaminophenanthrene with [{Rh(μ‐Cl)(ptpy)2}2] yields – quite unexpected – the new cyclometalated complex salts [Rh(ptpy)2(9,10‐diiminophenanthrene)]PF6 (1), whereas with the corresponding dinuclear iridium compound the “usual” [Ir(ptpy)2(9,10‐diaminophenanthrene)]PF6 (2) is obtained. The molecular structure of compound 1 was confirmed by single‐crystal X‐ray diffraction. 1 crystallized in the monoclinic space group P21/n as a dichloromethane solvate. Both compounds display significant cytotoxicity against human cancer cell lines with the IC50 values in the low micromolar range

Reirradiation as part of a salvage treatment approach for progressive non-pontine pediatric high-grade gliomas: preliminary experiences from the German HIT-HGG study group

Background and purpose: The aim of the present analysis was to assess the feasibility, toxicity, and the tumor control of reirradiation as a salvage treatment for progressive pediatric non-pontine high-grade gliomas (HGG). Patients and methods: The database of the Reference Center for Radiation Oncology of the German HIT (HIT = German acronym for brain tumor) treatment network for childhood brain tumors was screened for children who were reirradiated for progressive non-pontine HGG. Results: We identified eight patients (WHO grade III: n = 5; WHO grade IV: n = 3) who underwent reirradiation between April 2006 and July 2012. Median age was 13.5 years at primary diagnosis and 14.8 years at first progression. All patients initially underwent surgery (incomplete resection, n = 7; biopsy, n = 1) followed by radiochemotherapy. Relapses occurred inside (n = 2), at the margin (n = 4), and outside of the preirradiated area (n = 2). In all patients, reirradiation was tolerated well without significant acute toxicity. Temporary clinical improvement and tumor regression on magnetic resonance imaging (MRI) following reirradiation was reported (n = 3). However, all patients finally died by disease progression. Median survival time was 26.2 months from initial diagnosis and 11.4 months after first progression. Median time interval between initial radiotherapy and first reirradiation was 9.0 months. In six patients, all macroscopic tumor deposits were reirradiated. In these patients, median progression-free (overall) survival from the start of reirradiation was 2.4 (4.6) months. Conclusion: Our analysis, although based on a limited patient number, suggests that reirradiation of progressive non-pontine HGG is feasible in children. Benefit in terms of quality of life and/or survival needs to be assessed in a prospective and ideally in a randomized manner