Studies on the synthesis of bafilomycin A(1): stereochemical aspects of the fragment assembly aldol reaction for construction of the C(13)-C25) segment

Highly stereoselective syntheses of aldols 8a-c corresponding to the C(13)-C(25) segment of bafilomycin A(1) were developed by routes involving fragment assembly aldol reactions of chiral aldehyde 6a and the chiral methyl ketones 7. A remote chelation effect plays a critical role in determining the stereoselectivity of the key aldol coupling of 6a and the lithium enolate of 7b. The protecting group for C(23)-OH of the chiral aldehyde fragment also influences the selectivity of the lithium enolate aldol reaction. In contrast, the aldol reaction of 6a and the chlorotitanium enolates of 7a,c were much less sensitive to the nature of the C(15)-hydroxyl protecting group. Studies of the reactions of chiral aldehydes with Takai's (gamma-methoxyallyl)chromium reagent 40 are also described. The stereoselectivity of these reactions is also highly dependent on the protecting groups and stereochemistry of the chiral aldehyde substrates.     

Application of thiol-olefin co-oxygenation methodology to a new synthesis of the 1,2,4-trioxane pharmacophore

[reaction: see text] Thiol-olefin co-oxygenation (TOCO) of substituted allylic alcohols generates alpha-hydroxyperoxides that can be condensed in situ with various ketones to afford a series of functionalized 1,2,4-trioxanes in good yields. Manipulation of the phenylsulfenyl group in 4a allows for convenient modification to the spiro-trioxane substituents, and we describe, for the first time, the preparation of a new class of antimalarial prodrug.     

ADP-specific sensors enable universal assay of protein kinase activity

Two molecular sensors that specifically recognize ADP in a background of over 100-fold molar excess of ATP are described. These sensors are nucleic-acid based and comprise a general method for monitoring protein kinase activity. The ADP-aptamer scintillation proximity assay is configured in a single-step, homogeneous format while the allosteric ribozyme (RiboReporter) sensor generates a fluorescent signal upon ADP-dependent ribozyme self-cleavage. Both systems perform well when configured for high-throughput screening and have been used to rediscover a known protein kinase inhibitor in a high-throughput screening format.     

Teacher Mentoring as a Community Effort

This article presents the findings from a study of a mentoring program for novice mathematics and science teachers, which was provided by their teacher education program. This study reports the findings of interviews with novice math and science teachers, their mentors, and the mentoring program administrators to explore stakeholder perceptions of mentoring support. Findings suggest the importance of using multiple mentoring strategies to develop, support, and retain high‐quality math and science teachers in the teaching profession. This study contributes to what is known about the role that teacher education programs may play in mentoring novice math and science teachers who have graduated from their programs.     

Cyclic tetrapeptides via the ring contraction strategy: chemical techniques useful for their identification

Cyclic tetrapeptides are a class of natural products that have been shown to have broad ranging biological activities and good pharmacokinetic properties. In order to synthesise these highly strained compounds a ring contraction strategy had previously been reported. This strategy was further optimised and a suite of techniques, including the Edman degradation and mass spectrometry/mass spectrometry, were developed to enable characterisation of cyclic tetrapeptide isomers. An NMR solution structure of a cyclic tetrapeptide was also generated. To illustrate the success of this strategy a library of cyclic tetrapeptides was synthesised.     

Rationally designed nanostructures for surface-enhanced Raman spectroscopy

Research on surface-enhanced Raman spectroscopy (SERS) is an area of intense interest because the technique allows one to probe small collections of, and in certain cases, individual molecules using relatively straightforward spectroscopic techniques and nanostructured substrates. Researchers in this area have attempted to develop many new technological innovations including high sensitivity chemical and biological detection systems, labeling schemes for authentication and tracking purposes, and dual scanning-probe/spectroscopic techniques that simultaneously provide topographical and spectroscopic information about an underlying surface or nanostructure. However, progress has been hampered by the inability of researchers to fabricate substrates with the high sensitivity, tunability, robustness, and reproducibility necessary for truly practical and successful SERS-based systems. These limitations have been due in part to a relative lack of control over the nanoscale features of Raman substrates that are responsible for the enhancement. With the advent of nanotechnology, new approaches are being developed to overcome these issues and produce substrates with higher sensitivity, stability, and reproducibility. This tutorial review focuses on recent progress in the design and fabrication of substrates for surface-enhanced Raman spectroscopy, with an emphasis on the influence of nanotechnology.     

Dewatering characteristics of algae-containing alum sludge

The presence of algae in source waters not only causes problems in the water treatment process, but also complicates the treatment and disposal of sludge. This has become a major concern in Taiwan because of the increasing eutrophication of water sources. The purpose of this study was to determine the effects of algae during aging process on the characteristics of potable water treatment residuals and investigate their conditioning in order to provide water treatment plants with guidelines for treating algae-containing sludge. In this study, we measured the bound water content and CST to evaluate the influence of algae and their exudates on sludge conditioning. The change in zeta potential was monitored during sludge aging. During the aging process up to 5 days, the surface charge of sludge became more negative and the dewaterability was enhanced by algal exudates. Microphotographs of the algae-containing sludge suggest that algae and their exudates cause the bio-flocculation phenomenon.     

Self‐Assembly and Dispersion of Chromogenic Molecules: A Versatile and General Approach for Self‐Assessing Polymers

Summary: Self‐assessing polymer blends based on poly(ethylene terephthalate glycol) or linear low‐density polyethylene and small amounts (0.5–2% w/w) of chromogenic sensor dyes are prepared and investigated. The cyano‐substituted oligo(p‐phenylene vinylene) dyes employed in the study exhibit pronounced optical absorption changes upon self‐assembly, because of charge‐transfer interactions or conformation changes. The extent of dye aggregation (and therewith the optical absorption characteristics) in these blends is significantly influenced by exposure to external stimuli. Subjecting appropriately processed samples to either temperatures above their glass transition or mechanical deformation can significantly change the extent of aggregation, which in turn leads to a color change.

Mechano‐optical response of a 1.0% w/w LLDPE/C18‐RG blend film. Pristine films are orange due to aggregated dye molecules. Deformation leads to dispersion of the dye and irreversibly changes the color to yellow.     

Solvent effects in active-site molecular dynamics simulations on the binding of 8-methyl-N5-deazapterin and 8-methylpterin to dihydrofolate reductase

Molecular dynamics (MD) simulation methods have been used to study the active site of the ternary complex formed between avian dihydrofolate reductase (DHFR), NADPH cofactor, and the inhibitor 8-methyl-N5-deazapterin in aqueous solution. Spherical shells of water molecules (initially at the bulk-solvent density) are used to solvate the active site and the surrounding protein surface. Two models for treating the effects of the neglected bulk solvent are then considered. The tethered water (TW) model is characterized by the use of harmonic restraining potentials to tether the water molecules to their initial (bulk solvent) positions; whereas, in the capped water (CW) model, water molecules are prevented from escaping from the solvent shell by the use of half-harmonic potentials, but otherwise their motions within the solvation shell are unrestrained. As measured by overall rms differences between coordinates, the distribution of solvent molecules in the active-site region, and the numbers of hydrogen bonds, the TW model compares favorably with the CW model but requires far fewer water molecules, i.e., relatively small solvent shells. The smaller shells of unrestrained water (CW model) gave rise to a distortion in the orientation of the side chain of the active-site residue Tyr-31, whereas no such distortion was apparent in the TW model or for the larger solvent shells in the CW model. A value for the force constant of 0.005 kcal/mol/Å2 for the tethering potential [Solmajer and Mehler, Int. J. Quant. Chem., 44, 291 (1992)] gave satisfactory results for DHFR, although we found that distance-dependent dielectric functions were unable to reproduce accurately the effects of the explicit water models. The free-energy change for the mutation of 8-methyl-N5-deazapterin to 8-methylpterin was computed using both nonsolvated and solvated models. The solvated models gave free energy differences about 1 kcal/mol lower than for nonsolvated models, but the differences between solvated models was much less than 1 kcal/mol. Overall, the calculated differences in thermodynamic stability of the deazapterin and pterin complexes are in fair agreement with experiment, i.e., a small binding differential is predicted. © 1996 by John Wiley & Sons, Inc.     

C−H Functionalization of Commodity Polymers

Synthetic manipulation of polymer substrates is one of the oldest and most reliable methods to increase the functional diversity of soft materials. Modifying the chemical structure of polymers that are already produced on a commodity scale leverages the current high‐volume and low‐cost production of commodity plastics for the discovery of modern materials. A myriad of polymer C?H functionalization methods have been developed which enable the modification of material properties on both a laboratory and industrial scale. More recently, driven by advances in C?H activation, photoredox catalysis, and radical chemistry, chemoselective approaches have emerged as a means to impart precise functionality onto commodity polymer substrates. This Review discusses the historical significance of and contemporary advances in the C?H functionalization of commodity polymers. The conceptual approach outlined herein presents exciting new directions for the field, including increasing the value of otherwise pervasive materials, uncovering entirely new material properties, and a viable path to upcycle post‐consumer plastic waste.