O,N,N-Pincer ligand effects on oxidatively induced carbon–chlorine coupling reactions at palladium

The syntheses of two families of sterically tuneable O,N,N pro-ligands are reported, namely the 2-(phenyl-2′-ol)-6-imine-pyridines, 2-(C6H4-2′-OH),6-(CMe[double bond, length as m-dash]NAr)C5H3N [Ar = 4-i-PrC6H4 (HL1a), 2,6-i-Pr2C6H3 (HL1b)] and the 2-(phenyl-2′-ol)-6-(amino-prop-2-yl)pyridines, 2-(C6H4-2′-OH),6-(CMe2NHAr)C5H3N [Ar = 4-i-PrC6H4 (HL2a), 2,6-i-Pr2C6H3 (HL2b)], using straightforward synthetic approaches and in reasonable overall yields. Interaction of HL1a/c and HL2a/b with palladium(II) acetate affords the O,N,N-pincer complexes, [{2-(C6H4-2′-O)-6-(CMe[double bond, length as m-dash]NAr)C5H3N}Pd(OAc)] (Ar = 4-i-PrC6H4 (1a), 2,6-i-Pr2C6H3 (1b)) and [{2-(C6H4-2′-O)-6-(CMe2NHAr)C5H3N}Pd(OAc)] (Ar = 4-i-PrC6H4 (2a), 2,6-i-Pr2C6H3 (2b)), which can be readily converted to their chloride derivatives, [{2-(C6H4-2′-O)-6-(CMe[double bond, length as m-dash]NAr)C5H3N}PdCl] (Ar = 4-i-PrC6H4 (3a), 2,6-i-Pr2C6H3 (3b)) and [{2-(C6H4-2′-O)-6-(CMe2NHAr)C5H3N}PdCl] (Ar = 4-i-PrC6H4 (4a), 2,6-i-Pr2C6H3 (4b)), respectively, on reaction with an aqueous sodium chloride solution. Treating each of 3a, 3b, 4a and 4b with two equivalents of di-p-tolyliodonium triflate at 100 °C in a toluene/acetonitrile mixture affords varying amounts of 4-chlorotoluene along with the 4-iodotoluene by-product with the conversions highly dependent on the steric and backbone properties of the pincer complex employed (viz.4a > 3a > 4b > 3b); notably, the least sterically bulky and most flexible amine-containing 4a reaches 90% conversion to 4-chlorotoluene in 15 h as opposed to 17% for imine-containing 3b. In the case of 3a, the inorganic palladium species recovered from the reaction has been identified as the Pd(II) salt [{2-(C6H4-2′-O)-6-(CMe[double bond, length as m-dash]N(4-i-PrC6H4)C5H3N}Pd(NCMe)][O3SCF3] (5a), which was independently prepared by the reaction of 3a with silver triflate in acetonitrile. Single crystal X-ray structures are reported for HL1a, HL2a, 1a, 1b, 2a, 2b, 3a and 5a

Organo-palladium(II) complexes bearing unsymmetrical N,N,N-pincer ligands: synthesis, structures and oxidatively induced coupling reactions

The 2-(2'-aniline)-6-imine-pyridines, 2-(C6H4--2'-NH2)-6-(CMe=NAr)C5H3 N (Ar = 4-i-PrC6H4 (HL1a), 2,6-i-Pr2C6H3 (HL1b)), have been synthesised via sequential Stille cross-coupling, deprotection and condensation steps from 6-tributylstannyl-2-(2-methyl-1,3-dioxolan-2-yl)pyridine and 2-bromonitrobenzene. The palladium(II) acetate N,N,N-pincer complexes, [{2-(C6H4-2'-NH)-6-(CMe=NAr)C5H3N}Pd(OAc)] (Ar = 4-i-PrC6H4 (1a), 2,6-i-Pr2C6H3 (1b)), can be prepared by reacting HL1 with Pd(OAc) 2 or, in the case of 1a , more conveniently by the template reaction of ketone 2-(C6H4-2'-NH2)-6-(CMe=O)C5H3N, Pd(OAc)2 and 4-isopropylaniline; ready conversion of 1 to their chloride analogues, [{2-(C6H4-2'-NH)-6-(CMe=NAr)C5H3N}PdCl] (Ar = 4-i-PrC6H4 (2a), 2,6-i-Pr2C6H3 (2b)), has been demonstrated. The phenyl-containing complexes, [{2-(C6H4-2'-NH)-6-(CMe=NAr)C5H3N}PdPh] (Ar = 4-i-PrC6H4 (3a), 2,6-i-Pr2C6H3 (3b)), can be obtained by treating HL1 with (PPh3)2 PdPh(Br) in the presence of NaH or with regard to 3a, by the salt elimination reaction of 2a with phenyllithium

Genome-wide association studies in infectious diseases.

One of the most puzzling questions facingboth parents and pediatricians is whysome children suffer severe and life-threatening infections, while others who are exposedto the same pathogen remain uninfected orsuffer only mild illness. There is now growingevidence that differences in host genetics playa major role in determining susceptibility andoutcome of childhood infections,1 in additionto environmental factors such as pathogenvirulence and exposure dos

Formation of a unique 'unsupported' hydridic stannate(II).

The reaction of the amido-stannate LiSn(NMe2)3 with the phosphine-borane (t)Bu2PHBH3 gives the Sn(II) hydride [(Me2NH)2Li{BH3P((t)Bu)2}2Sn(H)]; the first example of a hydridic stannate(ii) that is not supported by transition metal or ligand bonding.This is the author accepted manuscript. The final version is available from Royal Society of Chemistry via http://dx.doi.org/10.1039/C6CC01885H

Predictors of improved biochemical progression free survival for salvage prostate bed radiotherapy after radical prostatectomy

Predictors of improved biochemical progression free survival for salvage prostate bed radiotherapy after radical prostatectom

Neurology Case Reporting: a call for all

From antiquity to present day, the act of recording and publishing our observations with patients remains essential to the art of medicine and the care of patients. Neurology is rich with case reports over the centuries. They contribute to our understanding and knowledge of disease entities, and are a cornerstone of our professional development as physicians and the care of our patients. This editorial seeks to enthuse and invigorate house staff and practicing physicians everywhere to continue the long and time-honored tradition of neurology case reporting

Generalization Mediates Sensitivity to Complex Odor Features in the Honeybee

Animals use odors as signals for mate, kin, and food recognition, a strategy which appears ubiquitous and successful despite the high intrinsic variability of naturally-occurring odor quantities. Stimulus generalization, or the ability to decide that two objects, though readily distinguishable, are similar enough to afford the same consequence [1], could help animals adjust to variation in odor signals without losing sensitivity to key inter-stimulus differences. The present study was designed to investigate whether an animal's ability to generalize learned associations to novel odors can be influenced by the nature of the associated outcome. We use a classical conditioning paradigm for studying olfactory learning in honeybees [2] to show that honeybees conditioned on either a fixed- or variable-proportion binary odor mixture generalize learned responses to novel proportions of the same mixture even when inter-odor differences are substantial. We also show that the resulting olfactory generalization gradients depend critically on both the nature of the stimulus-reward paradigm and the intrinsic variability of the conditioned stimulus. The reward dependency we observe must be cognitive rather than perceptual in nature, and we argue that outcome-dependent generalization is necessary for maintaining sensitivity to inter-odor differences in complex olfactory scenes

Gene diversity in grevillea populations introduced in Brazil and its implication on management of genetic resources.

A variabilidade isoenzimática para seis populações de Grevillea robusta, oriundas de um teste de procedências/progenies, implantado no delineamento em blocos casualizados com 5 plantas por parcela, no Sul do Brasil, é descrita. A estrutura genética da população foi analisada utilizando-se marcadores bioquímicos, aos 5 anos de idade, especificamente para os locos MDH-3, PGM-2, DIA-2, PO-1, PO-2, SOD-1, e SKDH-1. As procedências do norte de ocorrência natural (Rathdowney e Woodenbong) apresentaram divergência genética superior, em relação à média das progênies, considerando o número de alelos por locus, (Ap), a riqueza alélica (Rs), a diversidade genética de Nei (H), e o coeficiente de endogamia (f). A endogamia foi detectada em diversos graus. A testemunha comercial apresentou o maior coeficiente de endogamia, (f = 0,4448), comparativamente à média das procedências (f = 0,2306), possivelmente devido à insuficiente amostragem populacional na região de origem (Austrália). Apesar de sua ocorrência natural restrita, observou-se correlação positiva entre divergência genética e distância geográfica entre as populações originais. A distância genética e análise de cluster, baseada no modelo bayesiano, mostrou três grupos de procedências distintos: 1) Rathdowney- QLD e Woodenbong-QLD; 2) Paddy?s Flat-NSW; e 3) Mann River-NSW, Boyd River-NSW e a testemunha comercial (material utilizado no Brasil). O agrupamento da testemunha com as procedências Mann River-NSW e Boyd River-NSW sugere um maior potencial das procedências do norte para o melhoramento genético visando à produção de madeira no Brasil, devido a sua elevada diversidade genética e baixo coeficiente de endogamia

In vivo clearance of surfactant lipids during acute pulmonary inflammation.

BACKGROUND: A decrease in pulmonary surfactant has been suggested to contribute to the lung dysfunction associated with pulmonary inflammation. A number of studies have implicated surfactant clearance as a possible mechanism for altered pool sizes. The objective of the current study was to specifically investigate the mechanisms of surfactant clearance in a rodent model of acute pulmonary inflammation. METHODS: Inflammation was induced by intrapulmonary instillation of lipopolysaccharide (LPS: 100 μg/kg). Lipid clearance was assessed at 18 and 72 hours post-LPS instillation by intratracheal administration of radiolabel surfactant-like liposomes 2 hours prior to isolation and analysis of inflammatory cells and type II cells. RESULTS: At both 18 and 72 hours after LPS instillation there was significantly less radioactivity recovered in the lavage fluid compared to respective control groups (p < 0.05). At both time points, the number of cells recovered by lavage and their associated radioactivity was greater compared to control groups (p < 0.01). There was no difference in recovery of radioactivity by isolated type II cells or other cells obtained from enzymatic digestion of lung tissue. CONCLUSION: These results show that increased clearance of surfactant lipids in our model of acute pulmonary inflammation is primarily due to the inflammatory cells recruited to the airspace and not increased uptake by alveolar type II cells

Alpha-particle-induced complex chromosome exchanges transmitted through extra-thymic lymphopoiesis in vitro show evidence of emerging genomic instability

Human exposure to high-linear energy transfer α-particles includes environmental (e.g. radon gas and its decay progeny), medical (e.g. radiopharmaceuticals) and occupational (nuclear industry) sources. The associated health risks of α-particle exposure for lung cancer are well documented however the risk estimates for leukaemia remain uncertain. To further our understanding of α-particle effects in target cells for leukaemogenesis and also to seek general markers of individual exposure to α-particles, this study assessed the transmission of chromosomal damage initially-induced in human haemopoietic stem and progenitor cells after exposure to high-LET α-particles. Cells surviving exposure were differentiated into mature T-cells by extra-thymic T-cell differentiation in vitro. Multiplex fluorescence in situ hybridisation (M-FISH) analysis of naïve T-cell populations showed the occurrence of stable (clonal) complex chromosome aberrations consistent with those that are characteristically induced in spherical cells by the traversal of a single α-particle track. Additionally, complex chromosome exchanges were observed in the progeny of irradiated mature T-cell populations. In addition to this, newly arising de novo chromosome aberrations were detected in cells which possessed clonal markers of α-particle exposure and also in cells which did not show any evidence of previous exposure, suggesting ongoing genomic instability in these populations. Our findings support the usefulness and reliability of employing complex chromosome exchanges as indicators of past or ongoing exposure to high-LET radiation and demonstrate the potential applicability to evaluate health risks associated with α-particle exposure.This work was supported by the Department of Health, UK. Contract RRX95 (RMA NSDTG)