Asymmetric Synthesis of Both Enantiomers of Protected 5‐Hydroxynorvaline by Hetero‐Diels‐Alder Addition of ethyl 2‐Nitrosoacrylate to (R)‐ and (S)‐1‐Phenylbutyl Vinyl Ether

Both enantiomers of protected 5‐hydroxynorvaline were prepared by hetero‐Diels‐Alder addition of ethyl 2‐nitrosoacrylate to readily available (R)‐ and (S)‐1‐phenylbutyl vinyl ether and a further three‐step manipulation. Attempted synthesis of (±)‐vigabatrin from protected (±)‐5‐hydroxynorvaline was unsuccessful.     

Dinuclear Bis(1,2-diaryl-1,2-ethylenedithiolato)iron complexes: [FeIII2(L)4]n (n = 2-, 1-, 0, 1+)

The electronic structures of four members of the electron-transfer series [Fe2(1L)4]n (n = 2-, 1-, 0, 1+) have been elucidated in some detail by electronic absorption, IR, X-band electron paramagnetic resonance (EPR), and M?ssbauer spectroscopies where (1L)(2-) represents the ligand 1,2-bis(4-tert-butylphenyl)-1,2-ethylenedithiolate(2-) and (1L*)- is its pi-radical monoanion. It is conclusively shown that all redox processes are ligand-centered and that high-valent iron(IV) is not accessible. The following complexes have been synthesized: [FeIII2(1L*)2(1L)2]0 (1), [FeIII2(2L*)2(2L)2].2CH2Cl2 (1') where (2L)(2-) is 1,2-bis(p-tolyl)-1,2-ethylenedithiolate(2-) and (2L*)- represents its pi-radical monoanion, [Cp2Co][FeIII2(1L*))(1L)3].4(toluene).0.5Et2O (2), and [Cp2Co]2[FeIII2(1L)4].2(toluene) (3). The crystal structures of 1' and 2 have been determined by single-crystal X-ray crystallography at 100 K. The ground states of complexes have been determined by temperature-dependent magnetic susceptibility measurements and EPR spectroscopy: 1' and 1 are diamagnetic (S(t) = 0); 2 (S(t) = 1/2); 3 (S(t) = 0); the monocation [Fe(III)2(1L*)3(1L)]+ possesses an S(t) = 1/2 ground state (S(t) = total spin ground state of dinuclear species). All species contain pairs of intermediate-spin ferric ions (S(Fe) = 3/2), which are strongly antiferromagnetically coupled (H = -2JS(1).S(2), where S1 = S2 = 3/2 and J = approximately -250 cm(-1)).     

Reversible pH‐ and Photocontrollable Carbohydrate‐Based Surfactants

The parallel synthesis and properties of a library of photoswitchable surfactants comprising a hydrophobic butylazobenzene tail‐group and a hydrophilic carbohydrate head‐group, including the first surfactants to exhibit dual photo‐ and pH‐responsive behavior, is reported. This new generation of surfactants shows varying micelle morphologies, photocontrollable surface tension, and pH‐induced aggregation and adsorption.     

Enhanced permanganate chemiluminescence

The significant enhancement of acidic potassium permanganate chemiluminescence by Mn(II) results from the concomitant presence of permanganate and Mn(III) in the reagent solution, which enables rapid production of the excited Mn(II) emitter with a wide range of analytes. Furthermore, the key Mn(III) co-reactant can be quickly generated by reducing permanganate with sodium thiosulfate, instead of the slow (~24 h) equilibration required when Mn(ii) is used. The emission from reactions with analytes such as tyrosine and fenoterol was over two orders of magnitude more intense than with the traditional permanganate reagent.     

Simplex representation of molecular structure as universal QSAR/QSPR tool

Structural Chemistry - We review the development and application of the Simplex approach for the solution of various QSAR/QSPR problems. The general concept of the simplex method and its...     

SimLean: Utilising simulation in the implementation of lean in healthcare

Discrete-event simulation (DES) and lean are approaches that have a similar motivation: improvement of processes and service delivery. Both are being used to help improve the delivery of healthcare, but rarely are they used together. This paper explores from a theoretical and an empirical perspective the potential complementary roles of DES and lean in healthcare. The aim is to increase the impact of both approaches in the improvement of healthcare systems. Out of this exploration, the ‘SimLean’ approach is developed in which three roles for DES with lean are identified: education, facilitation and evaluation. These roles are demonstrated through three examples of DES in action with lean. The work demonstrates how the fusion of DES with lean can improve both stakeholder engagement with DES and the impact of lean.     

The SAMPL6 SAMPLing challenge: assessing the reliability and efficiency of binding free energy calculations

Journal of Computer-Aided Molecular Design - Approaches for computing small molecule binding free energies based on molecular simulations are now regularly being employed by academic and industry...     

Development of visually evoked cortical activity in infant macaque monkeys studied longitudinally with fMRI

We studied the development of visual activation longitudinally in two infant monkeys aged 103-561 days using the BOLD fMRI technique under opiate anesthesia and compared the results with those obtained in three adult animals studied under identical conditions. Visual activation in primary visual cortex, V1, was strong and reliable in monkeys of the youngest and oldest ages, showing that functional imaging techniques give qualitatively similar results in infants and adults. Visual activation in extrastriate areas involved in processing motion (MT/V5) and form (V4) was not evident in the younger animals, but became more adult-like in the older animals. This delayed onset of measurable BOLD responses in extrastriate visual cortex may reflect delayed development of visual responses in these areas, although at this stage it is not possible to rule out either effects of anesthesia or of changes in cerebral vascular response mechanisms as the cause. The demonstration of visually evoked BOLD responses in young monkeys shows that the BOLD fMRI technique can usefully be employed to address functional questions of brain development.     

Identification of Novel Inhibitors of Escherichia coli DNA Ligase (LigA)

Present in all organisms, DNA ligases catalyse the formation of a phosphodiester bond between a 3′ hydroxyl and a 5′ phosphate, a reaction that is essential for maintaining genome integrity during replication and repair. Eubacterial DNA ligases use NAD⁺ as a cofactor and possess low sequence and structural homology relative to eukaryotic DNA ligases which use ATP as a cofactor. These key differences enable specific targeting of bacterial DNA ligases as an antibacterial strategy. In this study, four small molecule accessible sites within functionally important regions of Escherichia coli ligase (EC-LigA) were identified using in silico methods. Molecular docking was then used to screen for small molecules predicted to bind to these sites. Eight candidate inhibitors were then screened for inhibitory activity in an in vitro ligase assay. Five of these (geneticin, chlorhexidine, glutathione (reduced), imidazolidinyl urea and 2-(aminomethyl)imidazole) showed dose-dependent inhibition of EC-LigA with half maximal inhibitory concentrations (IC₅₀) in the micromolar to millimolar range (11–2600 µM). Two (geneticin and chlorhexidine) were predicted to bind to a region of EC-LigA that has not been directly investigated previously, raising the possibility that there may be amino acids within this region that are important for EC-LigA activity or that the function of essential residues proximal to this region are impacted by inhibitor interactions with this region. We anticipate that the identified small molecule binding sites and inhibitors could be pursued as part of an antibacterial strategy targeting bacterial DNA ligases.