Structural and biological investigation of ferrocene-substituted 3-methylidene-1,3-dihydro-2H-indol-2-ones

The Knoevenagel condensation of 1,3-dihydro-2H-indol-2-one with ferrocene carboxaldehyde afforded an approximate 2:1 mixture of the geometrical isomers (E)- and (Z)-3-ferrocenylmethylidene-1,3-dihydro-2H-indol-2-one respectively in an overall 67% yield; the air and solution-stable isomers were readily separated by preparative thin layer chromatography and their structures were unequivocally elucidated in solution, by (1)H NMR spectroscopy, and in the solid phase, by X-ray crystallography; both isomers of displayed in vitro toxicity against B16 melanoma and Vero cell lines in the micromolar range and inhibited the kinase VEGFR-2 with IC(50) values of ca. 200 nM.

Synthesis of a 1,4-benzodiazepine containing palladacycle with in vitro anticancer and cathepsin B activity

The reaction of the five-membered C,N-palladacycle [(L)PdCl](2), where LH = 1-methyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one, with 1,2-ethanebis(diphenylphosphine), dppe, leads to the formation of the bridged palladacycle. [Pd(2)L(2)(mu-dppe)Cl(2)] 3, which was characterised in solution by (1)H and (31)P NMR spectroscopy and in the solid state by X-ray crystallography. Complex 3 was tested in vitro against a number of cell lines. For example, it inhibited K562 leukaemia cells with an IC(50) value of 4.3 microM (1 h exposure) and displayed cathepsin B inhibitory action with an IC(50) value of 3 microM.

Developing “middle leaders” in the public services? The realities of management and leadership development for public managers

Purpose – This paper aims to assess the actual contribution to organisational change of management and leadership development (MLD) activity for middle managers (MMs) in public service organisations (PSOs). Design/methodology/approach – Using the case study approach, the paper compares the content and outcomes of management and leadership training interventions for MMs in two large PSOs. The organisations, a fire brigade and a train operating company, are leaders in their sectors with respect to management development and “modernisation” of their services. Findings – The paper demonstrates how, in one case, MM development was largely an exercise in regulatory compliance, with little effect on individual MMs' performance or organisational outcomes. The second case demonstrates how MMs were effectively trained to enforce specific human resource policies which contributed to the successful implementation of top-down strategy yet paid little attention to the potential leadership role of MMs. Research limitations/implications – The paper highlights the need for further contextualised research at organisational level into the outcomes of MLD, especially in terms of different public service contexts. Practical implications – The paper demonstrates the dangers of designing and implementing development programmes without sufficient regard to professional practice and the realities of managerial discretion in PSOs. Originality/value – The paper provides an in-depth and contextualised insight into the conditions for success and failure in management development interventions in PSOs.

The UK WTC9/11 evacuation study: an overview of the methodologies employed and some preliminary analysis

This paper briefly describes the methodologies employed in the collection and storage of first-hand accounts of evacuation experiences derived from face-to-face interviews from evacuees from the World Trade Centre (WTC) Twin Towers complex on 11 Septebmer 2001 and the development of the High-rise Evacuation Evaluation Database (HEED). The main focus of the paper is to present a preliminary analysis of data derived from the evacuation of the North Tower.

Influence of a fed or fasted state on the s-IgA response to prolonged cycling in active men and women

This study investigated the effect of a fed or fasted state on the salivary immunoglobulin A (s-IgA) response to prolonged cycling. Using a randomized, crossover design, 16 active adults (8 men and 8 women) performed 2 hr of cycling on a stationary ergometer at 65% of maximal oxygen uptake on 1 occasion after an overnight fast (FAST) and on another occasion 2 hr after consuming a 2.2-MJ high-carbohydrate meal (FED). Timed, unstimulated whole saliva samples were collected immediately before ingestion of the meal, immediately preexercise, 5 min before cessation of exercise, immediately postexercise, and 1 hr postexercise. The samples were analyzed for s-IgA concentration, osmolality, and cortisol, and saliva flow rates were determined to calculate s-IgA secretion rate. Saliva flow rate decreased by 50% during exercise (p < .05), and s-IgA concentration increased by 42% (p < .05), but s-IgA secretion rate remained unchanged. There was a 37% reduction in s-IgA:osmolality postexercise (p < .05), and salivary cortisol increased by 68% (p < .05). There was no effect of FED vs. FAST on these salivary responses. The s-IgA concentration, secretion rate, and osmolality were found to be significantly lower in women than in men throughout the exercise protocol (p < .05); however, there was no difference between genders in saliva flow rate, s-IgA:osmolality ratio, or cortisol. These data demonstrate that a fed or fasted state 2 hr before exercise does not influence resting s-IgA or the response to prolonged cycling. Furthermore, these results show lower levels of s-IgA and osmolality in women than in men at rest.

Seven 3-methylidene-1H-indol-2(3H)-ones related to the multiple-receptor tyrosine kinase inhibitor sunitinib

The solid-state structures of a series of seven substituted 3-methylidene-1H-indol-2(3H)-one derivatives have been determined by single-crystal X-ray diffraction and are compared in detail. Six of the structures {(3Z)-3-(1H-pyrrol-2- ylmethylidene)-1H-indol-2(3H)-one, C13H10N2O, (2a); (3Z)-3-( 2-thienylmethylidene)-1H-indol-2(3H)-one, C13H9NOS, (2b); (3E)-3-(2-furylmethylidene)-1H-indol-2(3H)-one monohydrate, C13H9NO2 center dot H2O, (3a); 3-(1-methylethylidene)-1H-indol- 2(3H)-one, C11H11NO, (4a); 3-cyclohexylidene-1H-indol- 2(3H)-one, C14H15NO, (4c); and spiro[1,3-dioxane-2,3'-indolin]- 2'-one, C11H11NO3, (5)} display, as expected, intermolecular hydrogen bonding (N-H center dot center dot center dot O=C) between the 1H-indol-2(3H)-one units. However, methyl 3-(1-methylethylidene)- 2-oxo-2,3-dihydro-1H-indole-1-carboxylate, C13H13NO3, (4b), a carbamate analogue of (4a) lacking an N-H bond, displays no intermolecular hydrogen bonding. The structure of (4a) contains three molecules in the asymmetric unit, while (4b) and (4c) both contain two independent molecules.

Preparation, properties and applications of colloidal microgels

This chapter contains sections titled: - Introduction - Microgel preparation - Characterisation of microgels - Properties and applications - Conclusions