Derivatives of pentamidine designed to target the Leishmania lipophosphoglycan

The Leishmania lipophosphoglycan (LPG) is the most abundant cell surface glycoconjugate of a family of infectious protozoa. Pentamidine, a common drug used in the treatment of Leishmania infections, has been modified with boronic acids so that it might bind more selectively to the phosphodisaccharide repeating unit of the LPG. This could serve to target the drug to the protozoan surface and increase its efficacy in vivo.     

Comparison of total folate concentrations in foods determined by microbiological assay at several experienced U.S. commercial laboratories

Analysis of total folate concentration measured by microbiological assay in a variety of foods submitted in a routine manner to experienced laboratories that regularly perform folate analysis on fee-for-service basis was evaluated. Homogenates of fresh strawberries, frozen spinach, orange juice, frozen meat and vegetable pizza, dry macaroni, and dried pinto beans were prepared and stored under conditions previously determined to maintain stability of folate content. An aliquot of each composite and of 3 certified reference materials were sent on each of 4 occasions to 4 laboratories. Results for macaroni and pizza, the only folic acid-fortified foods, had considerably lower between-laboratory variation (CV(B)) with CV(B) of 9-11% versus >45% for other foods. Mean total folate ranged from 14 to 279 microg/100 g for a mixed vegetable reference material, from 5 to 70 microg/100 g for strawberries, and from 28 to 81 microg/100 g for wholemeal flour. Only 1 laboratory reported using a tri-enzyme extraction, and all laboratories used folic acid fortified foods as internal control materials. Users of commercial total folate analysis should understand the uncertainty in values determined by microbiological assay, particularly for foods containing primarily naturally occurring folate, which may not be apparent when replicate samples are not submitted for analysis.     

Relationship Between Professional Development,Teachers' Instructional Practices,and the Achievement of Students in Science and Mathematics

The purpose of this study was to examine the relationship between different types of professional development, teachers' instructional practices, and the achievement of students in science and mathematics. The types of professional development studied included immersion, examining practice, curriculum implementation, curriculum development, and collaborative work. Data regarding teachers' instructional practices and the amount of professional development were collected using teacher surveys. Ninety‐four middle school science teachers and 104 middle school mathematics teachers participated in the study. Student achievement was measured using eighth grade state science and mathematics achievement test data. Regression analyses suggested that for both science and mathematics teachers, examining practice and curriculum development were significantly related to the use of standards‐based instructional practices. Only curriculum development for mathematics teachers was significantly related to student achievement. Implications of results for the professional development of science and mathematics teachers are discussed.     

Positivity for Gaussian graphical models

Gaussian graphical models are parametric statistical models for jointly normal random variables whose dependence structure is determined by a graph. In previous work, we introduced trek separation, which gives a necessary and sufficient condition in terms of the graph for when a subdeterminant is zero for all covariance matrices that belong to the Gaussian graphical model. Here we extend this result to give explicit cancellation-free formulas for the expansions of non-zero subdeterminants.     

Synthesis and application of a new bisphosphite ligand collection for asymmetric hydroformylation of allyl cyanide

A series of mono- and bidentate phosphites was prepared with (S)-5,5',6,6'-tetramethyl-3,3'-di-tert-butyl-1,1'-biphenyl-2,2'-dioxy [(S)-BIPHEN] as a chiral auxiliary and screened in the asymmetric hydroformylation of allyl cyanide. These hydroformylation results were compared with those of two existing chiral ligands, Chiraphite and BINAPHOS, whose utility in asymmetric hydroformylation has been previously demonstrated. Bisphosphite 11 with a 2,2'-biphenol bridge was found to be the best overall ligand for asymmetric hydroformylation of allyl cyanide with up to 80% ee and regioselectivities (branch-to-linear ratio, b/l) of 20 with turnover frequency of 625 [h(-)(1)] at 35 degrees C. BINAPHOS gave enantioselectivities up to 77% ee when the reaction was conducted in either acetone or neat but with poor regioselectivity (b/l 2.8) and activities 7 times lower than that of 11. The product of allyl cyanide hydroformylation using (R,R)-11 was subsequently transformed into (R)-2-methyl-4-aminobutanol, a useful chiral building block. Single-crystal X-ray structures of (S,S)-11 and its rhodium complex 19 were determined.     

Dienophile twisting and substituent effects influence reaction rates of intramolecular Diels-Alder cycloadditions: a DFT study

Intramolecular cycloadditions of 5-vinyl-1,3-cyclohexadienes were studied with B3LYP/6-31G(d) density functional calculations. The one-atom tether dictates that the Z substituent becomes exo and the E substituent becomes endo in the TS. The geometry of the cycloaddition TS is typical of a pericyclic transformation except unusual twisting of the dienophile places the endo substituent in a relatively steric-free position and the exo substituent in a highly crowded position. The experimental rate differences between isomeric pairs of vinylcyclohexadienes can be explained by comparing reactant destabilization when a bulky group occupies the Z position of the starting alkene and transition state stabilization when a bulky group is endo in the cycloaddition TS.     

Intramolecular cycloadditions of cyclobutadiene with dienes: experimental and computational studies of the competing (2 + 2) and (4 + 2) modes of reaction

Highly functionalized, cyclobutene-containing adducts are afforded through intramolecular cycloadditions between cyclobutadiene and tethered dienes. The cycloaddition displays the following reactivity trend: cyclobutadiene serves as a dienophile in intramolecular reactions when it is connected to the diene through a four-atom tether. In cases where a three-atom linker separates the two reaction partners, the cyclobutadiene can function as both a diene and dienophile, affording a mixture of vinylcyclobutane (2 + 2) and cyclohexene-containing cycloadducts (4 + 2). Theoretical studies provide insight into the factors influencing the various pericyclic pathways operative in this system. In cases where cyclobutadiene functions as a diene to generate vinylcyclobutanes, these (2 + 2) adducts can be converted into the corresponding (4 + 2) cyclohexenyl products through a [3,3]-sigmatropic rearrangement.