Modeling the Signatures of Hydrides in Metalloenzymes: ENDOR Analysis of a Di-iron Fe(μ-NH)(μ-H)Fe Core

The application of 35 GHz pulsed EPR and ENDOR spectroscopies has established that the biomimetic model complex L(3)Fe(μ-NH)(μ-H)FeL(3) (L(3) = [PhB(CH(2)PPh(2))(3)](-)) complex, 3, is a novel S = (1)/(2) type-III mixed-valence di-iron II/III species, in which the unpaired electron is shared equally between the two iron centers. (1,2)H and (14,15)N ENDOR measurements of the bridging imide are consistent with an allyl radical molecular orbital model for the two bridging ligands. Both the (μ-H) and the proton of the (μ-NH) of the crystallographically characterized 3 show the proposed signature of a 'bridging' hydride that is essentially equidistant between two 'anchor' metal ions: a rhombic dipolar interaction tensor, T ≈ [T, -T, 0]. The point-dipole model for describing the anisotropic interaction of a bridging H as the sum of the point-dipole couplings to the 'anchor' metal ions reproduces this signature with high accuracy, as well as the axial tensor of a terminal hydride, T ≈ [-T, -T, 2T], thus validating both the model and the signatures. This validation in turn lends strong support to the assignment, based on such a point-dipole analysis, that the molybdenum-iron cofactor of nitrogenase contains two [Fe-H(-)-Fe] bridging-hydride fragments in the catalytic intermediate that has accumulated four reducing equivalents (E(4)). Analysis further reveals a complementary similarity between the isotropic hyperfine couplings for the bridging hydrides in 3 and E(4). This study provides a foundation for spectroscopic study of hydrides in a variety of reducing metalloenzymes in addition to nitrogenase.     

Three-dimensional coherent x-ray diffraction imaging of a ceramic nanofoam: determination of structural deformation mechanisms

Ultralow density polymers, metals, and ceramic nanofoams are valued for their high strength-to-weight ratio, high surface area, and insulating properties ascribed to their structural geometry. We obtain the labrynthine internal structure of a tantalum oxide nanofoam by x-ray diffractive imaging. Finite-element analysis from the structure reveals mechanical properties consistent with bulk samples and with a diffusion-limited cluster aggregation model, while excess mass on the nodes discounts the dangling fragments hypothesis of percolation theory.     

基于拉曼光谱的储层沥青热演化特征及其判别

为了明确储层沥青热演化程度与激光拉曼光谱的关系,利用拉曼光谱无损分析和流体包裹体方法,对黔西南白层地区储层沥青拉曼光谱进行了定量化描述,首先获取了储层沥青其伴生流体包裹体均一温度,然后获得了储层沥青拉曼光谱图,并对比标准沥青成熟度分布图,确定了储层沥青热演化程度及其特征.结果表明:黔西南白层地区存在晚三叠世(230 M...     

一类规划问题所给最优性必要条件的注记

本文指出了一类规划问题所给最优性必要条件中所存在的问题。对于一些带有附加项，（如（x^TDx)^1/2‖Sx‖p）的单目标规划问题一般都给出了一个类似集合Z^0 ，并以“Z^0为空集”作为一个前提条件。本文指出此条件太强，并论证了当只有Z^0为空集时，就可推出强最优性必要条件，而不必要求“x^0是最优解”。     

Practical outcomes of applying ensemble machine learning classifiers to High-Throughput Screening (HTS) data analysis and screening

Over the years numerous papers have presented the effectiveness of various machine learning methods in analyzing drug discovery biological screening data. The predictive performance of models developed using these methods has traditionally been evaluated by assessing performance of the developed models against a portion of the data randomly selected for holdout. It has been our experience that such assessments, while widely practiced, result in an optimistic assessment. This paper describes the development of a series of ensemble-based decision tree models, shares our experience at various stages in the model development process, and presents the impact of such models when they are applied to vendor offerings and the forecasted compounds are acquired and screened in the relevant assays. We have seen that well developed models can significantly increase the hit-rates observed in HTS campaigns.     

Suzuki-Miyaura approach to JNJ-26076713, an orally active tetrahydroquinoline-containing alphaVbeta3/alphaVbeta5 integrin antagonist. enantioselective synthesis and stereochemical studies

An improved scale-up synthesis was required for the alpha(V)beta(3)/alpha(V)beta(5) integrin antagonist 1, which had demonstrated oral efficacy in eye disease models of angiogenesis and vascular permeability. A stereodefined, quinoline-substituted, unsaturated ester was conveniently prepared by a Suzuki-Miyaura coupling to facilitate exploration of multiple methods of asymmetric reduction. The catalytic chiral hydrogenation of the corresponding unsaturated acid (Z-5b) with a ruthenium-based metal precursor and the (R)-XylPhanePhos ligand proved particularly efficient and economical. The resulting (3S)-quinoline-containing intermediate was reduced to an equal mixture of tetrahydroquinoline diastereomers. The undesired diastereomer could be recycled to the desired one by an oxidation/reduction protocol. The absolute stereochemistry of 1 was established as 3S,3'S by a combination of X-ray diffraction and chemical means.     

Precision Rosenbluth measurement of the proton elastic form factors

We report the results of a new Rosenbluth measurement of the proton electromagnetic form factors at Q2 values of 2.64, 3.20, and 4.10 GeV2. Cross sections were determined by detecting the recoiling proton, in contrast to previous measurements which detected the scattered electron. Cross sections were determined to 3%, with relative uncertainties below 1%. The ratio mu(p)G(E)/G(M) was determined to 4%-8% and showed mu(p)G(E)/G(M) approximately 1. These results are consistent with, and much more precise than, previous Rosenbluth extractions. They are inconsistent with recent polarization transfer measurements of similar precision, implying a systematic difference between the techniques.