Synthesis of Complex Druglike Molecules by the Use of Highly Functionalized Bench‐Stable Organozinc Reagents

The reactivity of a representative set of 17 organozinc pivalates with 18 polyfunctional druglike electrophiles (informers) in Negishi cross‐coupling reactions was evaluated by high‐throughput experimentation protocols. The high‐fidelity scaleup of successful reactions in parallel enabled the isolation of sufficient material for biological testing, thus demonstrating the high value of these new solid zinc reagents in a drug‐discovery setting and potentially for many other applications in chemistry. Principal component analysis (PCA) clearly defined the independent roles of the zincates and the informers toward druggable‐space coverage.     

Simple and Efficient Ruthenium‐Catalyzed Oxidation of Primary Alcohols with Molecular Oxygen

Oxidative transformations utilizing molecular oxygen (O₂) as the stoichiometric oxidant are of paramount importance in organic synthesis from ecological and economical perspectives. Alcohol oxidation reactions that employ O₂ are scarce in homogeneous catalysis and the efficacy of such systems has been constrained by limited substrate scope (most involve secondary alcohol oxidation) or practical factors, such as the need for an excess of base or an additive. Catalytic systems employing O₂ as the “primary” oxidant, in the absence of any additive, are rare. A solution to this longstanding issue is offered by the development of an efficient ruthenium‐catalyzed oxidation protocol, which enables smooth oxidation of a wide variety of primary, as well as secondary benzylic, allylic, heterocyclic, and aliphatic, alcohols with molecular oxygen as the primary oxidant and without any base or hydrogen‐ or electron‐transfer agents. Most importantly, a high degree of selectivity during alcohol oxidation has been predicted for complex settings. Preliminary mechanistic studies including ¹⁸O labeling established the in situ formation of an oxo–ruthenium intermediate as the active catalytic species in the cycle and involvement of a two‐electron hydride transfer in the rate‐limiting step.     

Self‐assembly of di‐ and triblock PEG‐pentavaline amphiphiles

Nanoparticles formed from amphiphilic block copolymers can be used as drug delivery vehicles for hydrophilic therapeutics. Poly(ethylene glycol) (PEG)‐peptide copolymers were investigated for their self‐assembling properties and as consequent potential delivery systems. Mono‐ and dihydroxy PEGs were functionalized with a pentavaline sequence bearing Fmoc end groups. The molecular weight of the PEG component was varied to evaluate copolymer size and block number. These di‐ and tri‐block copolymers readily self‐assemble in aqueous solution with critical aggregation concentrations (CACs) of 0.46–16.29 μM. At concentrations above the CAC, copolymer solutions form spherical assemblies. Dynamic light scattering studies indicate these aggregates have a broad size distribution, with average diameters between 33 and 127 nm. The copolymers are comprised β‐conformations that are stable up to 80 °C, as observed by circular dichroism. This peptide secondary structure is retained in solutions up to 50% MeOH as well. The triblock copolymers proved to be the most stable, with copolymers synthesized from 10 kDa PEG having the most stable particles. Loading of carboxyfluorescein at 2–5 mol % shows that these copolymers have the potential to encapsulate hydrophilic drugs for delivery applications. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Simplest Prussian-blue deposition from ferric ferricyanide solution by a reducing Ag spot put onto an ITO substrate

Prussian-blue (PB) film for electro-chromism can be electro-deposited on to an electrode (usually tin-doped indium oxide/glass) either directly from a PB colloid or from ferric ferricyanide in a two-electrode electro-chemical cell by applying a reductive potential. Alternatively, a “sacrificial” electron-producing silver flag electrode in the solution, when connected to the PB-receiving electrode, can effect the required reductive deposition. A silver spot, here innovatively applied as silver paint directly onto the deposition electrode, produces PB film on immersion in the iron(III)(III) solution, obviating the separate counter-electrode method.     

ASSESSING EARLY MATHEMATICAL DEVELOPMENT

The work discussed here is part of an international study involving Dutch, Belgian, German, Greek, Finnish and Slovenian as well as English children aged between 52 and 98 months. The project is coordinated by the University of Utrecht and employs the Utrecht Early Mathematical Competence Test. The full international data set is currently being analysed. This paper reports only the analysis of the English data, together with some international data already in the public domain. The data are interrogated to throw light upon (a) the comparison between England and other countries, (b) the relationship between age and mathematical attainment in the English sample, (c) differences between boys and girls and (d) the relationship between attainment in Piagetian tasks and more arithmetical tasks.     

Isolation of a new triterpene derivative and in vitro and in vivo anticancer activity of ethanolic extract from root bark of Zizyphus nummularia Aubrev

The various parts of Zizyphus nummularia has been used traditionally in several disease conditions. However, its anticancer activity and mechanism of action remain to be elucidated. Considering this, the objective of this study was to isolate, identify and screen for possible anticancer activity in vitro and in vivo of the ethanolic extract (EE) and isolated identified compound (IC) from Z. nummularia root bark. The in vitro activity against human breast cancer, leukaemia, ovarian cancer, colon adenocarcinoma and human kidney carcinoma cell lines was determined. The in vivo activity in female Swiss albino mice against Ehrlich ascites carcinoma (EAC) was determined. The isolated compound is a new triterpene derivative. EE/IC showed cytotoxicity against different cell lines. The administration of EE/IC decreased tumour parameters such as tumour volume, viable tumour cell count and increased body weight, haematological parameters and life span in comparison to the EAC control mice.