Chiral iridium [corrected] xyliphos complexes for the catalytic imine hydrogenation leading to the metolachlor herbicide: isolation of catalyst-substrate adducts

Iridium complexes relevant to the catalytic enantioselective hydrogenation of 2-methyl-6-ethylphenyl-1'-methyl-2'-methoxyethylimine (MEA-imine, 1) in the Syngenta Metolachlor (3) process were prepared and characterized. Reaction of the diphosphane (S)-1-[(R)-2-(diphenylphosphanyl)ferrocenyl]ethyldi(3,5-xylyl)phosphane ((S)-(R)-Xyliphos, (S)-(R)-4) with [Ir(2)(micro-Cl)(2)(cod)(2)] (cod=1,5-cyclooctadiene) afforded [Ir(Cl)(cod)[(S)-(R)-4]] (7), which reacted with AgBF(4) to form [Ir(cod)[(S)-(R)-4]]BF(4) (8). Complexes 7 and 8 reacted with iodide to yield [Ir(I)(cod)[(S)-(R)-4]] (9). When 9 was treated with one and two equivalents of HBF(4), two isomers of the cationic Ir(III) iodo hydrido complex [Ir(I)(H)(cod)[(S)-(R)-4]]BF(4) were solated (10 and 11, respectively). Complex 9 was oxidized with one equivalent of I(2) to give the iodo-bridged dinuclear species [Ir(2)I(2)(micro-I)(3)[(S)-(R)-4](2))]I (12). [Ir(2)(micro-Cl)(2)(coe)(4)] (coe=cyclooctene) reacted with (S)-(R)-4 to yield the chloro-bridged dinuclear complex [Ir(2)(micro-Cl)(2)[(S)-(R)-4](2)] (13). Complexes 7-12 were structurally characterized by single-crystal X-ray diffraction and tested as single-component catalyst precursors for enantioselective hydrogenation of MEA-imine. Complex 10 and dinuclear complex 12 gave the best catalytic results. Efforts were also directed at isolating substrate- or product-catalyst adducts: Treatment of 8 with 2,6-dimethylphenyl-1'-methyl-2'-methoxyethylimine (DMA-imine, 14, a model for 1) under H(2) allowed four isomers of [Ir(H)(2)[(S)-(R)-4](14)]BF(4) (18-21) to be isolated. These analytically pure isomers were fully characterized by 2D NMR techniques. X-ray structural analysis of an Ir(I)-imine adduct, namely, [Ir(C(2)H(4))(2)(14)]BF(4) (25), which was prepared by reacting [IrCl(C(2)H(4))(4)] with [Ag(14)(2)]BF(4) (16), confirmed the kappa(2) coordination mode of imine 14.     

An ontology for pharmaceutical ligands and its application for in silico screening and library design

Annotation efforts in biosciences have focused in past years mainly on the annotation of genomic sequences. Only very limited effort has been put into annotation schemes for pharmaceutical ligands. Here we propose annotation schemes for the ligands of four major target classes, enzymes, G protein-coupled receptors (GPCRs), nuclear receptors (NRs), and ligand-gated ion channels (LGICs), and outline their usage for in silico screening and combinatorial library design. The proposed schemes cover ligand functionality and hierarchical levels of target classification. The classification schemes are based on those established by the EC, GPCRDB, NuclearDB, and LGICDB. The ligands of the MDL Drug Data Report (MDDR) database serve as a reference data set of known pharmacologically active compounds. All ligands were annotated according to the schemes when attribution was possible based on the activity classification provided by the reference database. The purpose of the ligand-target classification schemes is to allow annotation-based searching of the ligand database. In addition, the biological sequence information of the target is directly linkable to the ligand, hereby allowing sequence similarity-based identification of ligands of next homologous receptors. Ligands of specified levels can easily be retrieved to serve as comprehensive reference sets for cheminformatics-based similarity searches and for design of target class focused compound libraries. Retrospective in silico screening experiments within the MDDR01.1 database, searching for structures binding to dopamine D2, all dopamine receptors and all amine-binding class A GPCRs using known dopamine D2 binding compounds as a reference set, have shown that such reference sets are in particular useful for the identification of ligands binding to receptors closely related to the reference system. The potential for ligand identification drops with increasing phylogenetic distance. The analysis of the focus of a tertiary amine based combinatorial library compared to known amine binding class A GPCRs, peptide binding class A GPCRs, and LGIC ligands constitutes a second application scenario which illustrates how the focus of a combinatorial library can be treated quantitatively. The provided annotation schemes, which bridge chem- and bioinformatics by linking ligands to sequences, are expected to be of key utility for further systematic chemogenomics exploration of previously well explored target families.     

The Analysis of Mammalian Hearing Systems Supports the Hypothesis That Criticality Favors Neuronal Information Representation but Not Computation

In the neighborhood of critical states, distinct materials exhibit the same physical behavior, expressed by common simple laws among measurable observables, hence rendering a more detailed analysis of the individual systems obsolete. It is a widespread view that critical states are fundamental to neuroscience and directly favor computation. We argue here that from an evolutionary point of view, critical points seem indeed to be a natural phenomenon. Using mammalian hearing as our example, we show, however, explicitly that criticality does not describe the proper computational process and thus is only indirectly related to the computation in neural systems.     

The doubly-magic character of146Gd and its relation to208Pb

Recent experiments indicate the possibility of a doubly-magic character for the nucleus¹⁴⁶Gd (Z=64, N=82). In this work the results of a large-scale shell-model study on the nucleus¹⁴⁶Gd and its neighbouring nuclei¹⁴⁵Eu,¹⁴⁵Gd,¹⁴⁷Gd and¹⁴⁷Tb are presented. The configurations taken into account include up to 2p - 2h excitations for protons and/or neutrons. The calculated spectra and static moments are compared with the experimental data. Finally, the present results on shell closure in¹⁴⁶Gd are discussed in connection with those derived from a similar approach applied to the well-known doubly-magic nucleus²⁰⁸Pb.     

主观评价实验中声音样本剂量值的度量方法

提出了一种基于对播放时长短时化处理的声音样本剂量值度量方法, 确定了十一种剂量值指标用于衡量具有固定播放时长声音样本的剂量值, 并分析了可能影响声音样本剂量值的主要因素; 随后, 对大量声音样本以各种指标度量的剂量值矩阵进行了聚类分析, 获得了三种类型的声音样本剂量值度量指标, 并确定了不同指标类型中的代表性指标; 最后, 分析了声音样本采用不同类型指标度量的剂量值与评价者对声音样本主观烦恼度等级之间的关系. 为利用主观评价实验进行固定播放时长声音样本作用下的主观烦恼度研究奠定了基础. 关键词： 声暴露量 烦恼度 声音样本 主观评价     

Antimony biomethylation by mixed cultures of micro-organisms under anaerobic conditions

The volatile antimony compound trimethylantimony (TMA) was detected in headspace gases over anaerobic soil enrichment cultures spiked with potassium antimony tartrate. The presence of TMA was variable (12 positives from 104 cultures) and dependent upon both the inoculum source (environmental sample) and enrichment culture conditions. Positives for TMA formation were obtained with variable frequency for four of the six soils tested and for three types of enrichment culture, designed to encourage growth of nitrate-reducing, methane-producing or fermentative bacteria. The identity of the volatile antimony compound produced in each of the three types of enrichment culture was confirmed by gas chromatography–mass spectrometry and gas chromatography–atomic absorption spectroscopy. There was no evidence of any other volatile antimony compound in the headspace gases. These data suggest that the capability to generate TMA is widely distributed in the terrestrial environment and is attributable to different metabolic types of micro-organisms. © 1998 John Wiley & Sons, Ltd.