Structure of an 11-Membered Cyclic Silyl Enol Ether from Condensation of Methacrolein and a Pseudoephedrine-Derived O-Silyl Ketene N,O -Acetal

The title compound, (4S,5S,8R, IOZ)-2,2,5,6,8,10-hexamethyl-4-phenyl- 1,3-dioxa-6-aza-2-silacycloun-dec-10-en-7-one, crystallizes with two virtually identical molecules in the asymmetric unit, each with the same absolute configuration. Bond distances and angles are normal; the closest approaches across the ring between non-bonded atoms are all greater than 3.35 .A,. The amide and enol ether groups are planar to within +- 0.06 A.Chemistry and Chemical Biolog

Structures of Two Diastereomeric Aldol Products from a New Silicon-Directed Condensation

Hexahydro-3,3,6-trimethyl-5-phenyl- 1 H,7H-pyrrolo[2,1-e][1,3,6,2]dioxazasilonin-7-one, C17H25NO3Si, Mr=319.48. (2S,3R)-anti-Diastereomer (I), orthorhombic, P212121, a= 8-716(4), b=11-677(3), c=17.161(6)A, V=1746(1)A3, Z=4, Dx=1.22 g cm-3, wavelength(Mo Kce) = 0.71073 A, u=1.50 cm-1 F(000)=688, room temperature, final R=0.040 for 1683 reflections with Fo2 greater than 0. (2S,3S)-syn- Diastereomer (II), monoclinic, P21, a=6.633(2), b=14.645(3), c=9.630(2) A, Beta=109.96(2)o, V=879.3(4) A3, Z=2, Dx=1.21 g cm-3, wavelength(Mo Ka)=0.71073 A,u = 1-49 cm-1, F(000)=344, room temperature, final R = 0.042 for 2537 reflections with F2o greater than 0. The compounds have a nine-membered hetero-cyclic ring containing the Si atom, the N atom of the pyrrolidine ring, two O atoms bonded to silicon and a carbonyl C atom. Bond distances in the molecules are normal and equivalent bonds are equal within three times their e.s.d.'s. Isomer (I) shows a disorder in the pyrrolidine ring that is absent in isomer (II).Chemistry and Chemical Biolog

Structure of a Syn Aldol Addition Product of Benzaldehyde and A Prolinol-Derived O-Silacyclopentyl Ketene N,O-Acetal

The compound (5S,6S,11 aS)-hexahydro-6-methyl-5-phenylspiro[1H,7H-pyrrolo[2,1-e][1,3,6,2]dioxazasilonine-3,1'-silacyclopentan]-7-one (1) results from the silicon-directed condensation of the prolinol-derived O-silacyclopentyl ketene N,O-acetal (2) with benzaldehyde. The five-membered pyrrolidine ring has an envelope conformation and the silacyclopentyl ring has an en-type conformation with C17 and C18 on opposite sides of the CI6--Si--C19 plane. Both of these rings appear to be disordered.Chemistry and Chemical Biolog

Structure of a Chiral Cyelopentanone Precursor in Neocarzinostatin Synthetic Studies, C20H21NO3S.H20

(1E,2S,3R)-2-[(4R,5R)-4,5-Dimethyl-l,3-dioxolan-2-yl]-3-(2-naphthylthio)cyclopentanone oxime, 3//,=373.47, orthorhombic, P212121, a = 5-374 (13), b = 18.135 (3), c= 20.487 (5) A, V = 1997 (5)/~3, Z = 4, Dx = 1.24 g cm -3, Mo Ka, a = 0.71073/~, /z = 1-87 cm-1, F(000) = 792, room temperature, crystal volume 2.7 x 10 -4 mm 3, final R = 0.127 for 971 reflections with Fo2>0 out of 1131 data, R = 0.065 for 467 reflections with Fo 2 > 3o'(Fo2). Despite the small crystal size (all larger crystals were twinned), a structural solution of adequate precision was obtained. Bond distances and angles in the molecule are normal; the water molecules are hydrogen bonded in a chain along the a axis and each accepts a hydrogen bond from the oxime group and donates a weak hydrogen bond to 03 in the dioxolane group.Chemistry and Chemical Biolog

Structure of an anti-Aldol Addition Product of Benzaldehyde and a Pseudoephedrine-Derived O-Silyl Ketene N,O-Acetal

[4S-(4R*,5R*,8R*,9S*)]-2,2,5,6,8-Penta- methyl-4,9-diphenyl- 1,3-dioxa-6-aza-2-silacyclono-nan-7-one, CE2H29NO3Si, Mr = 383.56, monoclinic, P21, a = 6.550 (3), b = 17.318 (6), c = 20.129 (6) A, /3=98.83(3)° , V =2256.2(14) A 3, Z=4, Dx= 1.13 gcm -3, A(Mo Ka) = 0.71073 A,/z = 1.18 cm -1, F(000) = 824, room temperature, R on F = 0.039 for 4305 reflections with Fo 2 > 3cr(Fo2). The two independent molecules in this structure have nearly the same configuration and geometry. The Si atoms are tetrahedrally coordinated, with average Si--C bond distances of 1.842(3)/~ and average Si---O bond distances of 1.636 (7)A; angles at Si differ from 109.5 ° by an average of 3.5 °. The nine-membered rings are fully extended and the planes of the phenyl groups are approximately perpendicular to the nine- membered ring.Chemistry and Chemical Biolog

Regionalization of Flood Data Using Probability Distributions and Their Parameters

The U. S. Geological survey recently used the method of residuals to delineate seven flood regions for the State of Kentucky. As an alternative approach, the FASTCLUS clustering procedure of the Statistical Analysis system (SAS) is used in this study to delineate five to six cluster regions in conjunction with statistical properties of the AMF series, like the coefficient of variation as estimated using method of L-moments, LCV, the parameters of the EVl and GEV flood frequency distributions, and the specific mean annual flood, QSP. For both cluster and USGS flood regions, regionalized flood frequency growth curves are developed and their performance evaluated using Monte Carlo simulation techniques. Flood regions are.then evaluated and compared ·using trends in the hydrological characteristics of important.variables, performance of the regionalized flood frequency growth curves, discriminant analysis and regression equations relating flood quantiles to watershed physical characteristics. Results show that the cluster regions are more distinguishable in terms of their flood characteristics than the USGS regions. The.regionalized flood frequency growth curves of the EVl and GEV model are more distinct for the cluster regions than the USGS regions, although their performance in terms of bias and RMSE are comparable. The standard errors associated with the regression equations, developed for predicting the EVl and GEV flood quantiles, are similar for cluster and USGS regions

Nanoparticles modified with multiple organic acids

Surface-modified nanoparticles of boehmite, and methods for preparing the same. Aluminum oxyhydroxide nanoparticles are surface modified by reaction with selected amounts of organic acids. In particular, the nanoparticle surface is modified by reactions with two or more different carboxylic acids, at least one of which is an organic carboxylic acid. The product is a surface modified boehmite nanoparticle that has an inorganic aluminum oxyhydroxide core, or part aluminum oxyhydroxide core and a surface-bonded organic shell. Organic carboxylic acids of this invention contain at least one carboxylic acid group and one carbon-hydrogen bond. One embodiment of this invention provides boehmite nanoparticles that have been surface modified with two or more acids one of which additional carries at least one reactive functional group. Another embodiment of this invention provides boehmite nanoparticles that have been surface modified with multiple acids one of which has molecular weight or average molecular weight greater than or equal to 500 Daltons. Yet, another embodiment of this invention provides boehmite nanoparticles that are surface modified with two or more acids one of which is hydrophobic in nature and has solubility in water of less than 15 by weight. The products of the methods of this invention have specific useful properties when used in mixture with liquids, as filler in solids, or as stand-alone entities

Structure of Metallathiacycles: Planar vs Nonplanar Geometries. A Theoretical and Experimental Investigation

Since the previously reported results of Fenske-Hall molecular orbital calculations suggested that the bent metallacycle geometries observed in transition-metal-inserted thiophene complexes do not result from electronic properties, molecular mechanics calculations were employed to explore how steric factors could influence ring geometries. These calculations have identified steric factors responsible for the observed ring deformations in (C 5 Me 5 )Rh(PMe 3 )(η 2 -C,S-2,5-Me 2 C 4 H 2 S) and benzothiophene and dibenzothiophene analogs. The results of the molecular mechanics calculations have been supported by X-ray structural characterization of the products formed via insertion of the reactive 16-electron metal fragment [(C 5 Me 5 )Rh(PMe 3 )] into the C-S bonds of unsubstituted thiophene, benzothiophene, and dibenzothiophene. The parent thiophene complex, unlike the previously reported ringsubstituted analog (and as predicted by the molecular mechanics calculations) is found to adopt a planar six-membered ring structure. The benzothiophene insertion product shows a moderate degree of bending of the metallathiacycle, whereas the dibenzothiophene molecule is strongly bent

A platform for the discovery of new macrolide antibiotics.

The chemical modification of structurally complex fermentation products, a process known as semisynthesis, has been an important tool in the discovery and manufacture of antibiotics for the treatment of various infectious diseases. However, many of the therapeutics obtained in this way are no longer effective, because bacterial resistance to these compounds has developed. Here we present a practical, fully synthetic route to macrolide antibiotics by the convergent assembly of simple chemical building blocks, enabling the synthesis of diverse structures not accessible by traditional semisynthetic approaches. More than 300 new macrolide antibiotic candidates, as well as the clinical candidate solithromycin, have been synthesized using our convergent approach. Evaluation of these compounds against a panel of pathogenic bacteria revealed that the majority of these structures had antibiotic activity, some efficacious against strains resistant to macrolides in current use. The chemistry we describe here provides a platform for the discovery of new macrolide antibiotics and may also serve as the basis for their manufacture

Credible practice of modeling and simulation in healthcare: ten rules from a multidisciplinary perspective

The complexities of modern biomedicine are rapidly increasing. Thus, modeling and simulation have become increasingly important as a strategy to understand and predict the trajectory of pathophysiology, disease genesis, and disease spread in support of clinical and policy decisions. In such cases, inappropriate or ill-placed trust in the model and simulation outcomes may result in negative outcomes, and hence illustrate the need to formalize the execution and communication of modeling and simulation practices. Although verification and validation have been generally accepted as significant components of a model\u27s credibility, they cannot be assumed to equate to a holistic credible practice, which includes activities that can impact comprehension and in-depth examination inherent in the development and reuse of the models. For the past several years, the Committee on Credible Practice of Modeling and Simulation in Healthcare, an interdisciplinary group seeded from a U.S. interagency initiative, has worked to codify best practices. Here, we provide Ten Rules for credible practice of modeling and simulation in healthcare developed from a comparative analysis by the Committee\u27s multidisciplinary membership, followed by a large stakeholder community survey. These rules establish a unified conceptual framework for modeling and simulation design, implementation, evaluation, dissemination and usage across the modeling and simulation life-cycle. While biomedical science and clinical care domains have somewhat different requirements and expectations for credible practice, our study converged on rules that would be useful across a broad swath of model types. In brief, the rules are: (1) Define context clearly. (2) Use contextually appropriate data. (3) Evaluate within context. (4) List limitations explicitly. (5) Use version control. (6) Document appropriately. (7) Disseminate broadly. (8) Get independent reviews. (9) Test competing implementations. (10) Conform to standards. Although some of these are common sense guidelines, we have found that many are often missed or misconstrued, even by seasoned practitioners. Computational models are already widely used in basic science to generate new biomedical knowledge. As they penetrate clinical care and healthcare policy, contributing to personalized and precision medicine, clinical safety will require established guidelines for the credible practice of modeling and simulation in healthcare