Friction and inertia: business change, corporate real estate portfolios and the UK office market

It has been asserted that business reorganisation and new working practices are transforming the nature of demand for business space. Downsizing, delayering, business process reengineering and associated initiatives alter the amount, type and location of space required by firms. The literature has neglected the impact of real estate market structures on the ability of organisations to successfully implement these new organisational forms or contemporary working practices. Drawing from UK research, the paper demonstrates that, while new working practices are widespread, their impact on the corporate real estate portfolio is less dramatic than often supposed. In part, this is attributed to inflexibility in market structures which constrains the supply of appropriate space

Diversity oriented synthesis : substitution at C5 in unreactive pyrimidines by Claisen rearrangement and reactivity in nucleophilic substitution at C2 and C4 in pteridines and pyrido[2,3-d]pyrimidines

Diversity oriented synthesis of fused pyrimidines leads to scaffolds with many biological activities. In the case of the preparation of pyrido[2,3-d]pyrimidines from 2-alkylthiopyrimidines, the formation of a new carbon-carbon bond at C5 is required, a reaction that is very limited in scope. However Claisen type rearrangement of simple 4-allylic ethers affords C5 substituted pyrimidines readily; in cases with an ester substituent, rearrangement occurs at room temperature. Subsequent cyclisation to afford 6-methylpyrido[2,3-d]pyrimidin-7(8H)-ones was achieved in high yield. Using allylic ethers derived from 3-chloromethyl-4-arylbut-3-en-2-ones as substrates, a new titanium[IV]chloride catalysed reaction affording 6-arylmethyl-7-methylpyrido[2,3-d]pyrimidines was discovered. In contrast, 2-alkylthiopteridines are readily available. In both cases, substitution at C2 and C4 to generate diversity has been carried out and the reactivity compared; yields of substitution products were generally higher with pteridine substrates. In biological assays unexpected hits were found for activity against the Gram positive bacterium, Nocardia farcinia, and against the parasite Trypanosoma brucei brucei, illustrating the value of diversity oriented synthesis in the discovery of biologically active compound

Friction and Inertia: Business Change, Corporate Real Estate Portfolios and the U.K. Office Market

It has been asserted that business reorganization and new working practices are transforming the nature of demand for business space. Downsizing, delayering, business process re-engineering and associated initiatives alter the amount, type and location of space required by firms. The literature has neglected the impact of real estate market structures on the ability of organizations to implement these new organizational forms or contemporary working practices successfully. Drawing from research in the United Kingdom, the article demonstrates that, while new working practices are widespread, their impact on the corporate real estate portfolio is less dramatic than often supposed. In part, this is attributed to inflexibility in market structures, which constrains the supply of appropriate space.

Investigations into Ambient Ionization Mechanisms: Electrospray Ionization and Direct Analysis in Real Time Mass Spectrometry

Mass spectrometry (MS) is an important tool for chemical analyses. Despite the MS requirement for generation of analyte gas-phase ions, many ion source designs afford little-to-no fragmentation, allowing characterization of intact molecules. However, this does not assure that detected ions are representative of the analytes’ natural state. Ionization mechanisms are generally complex and rarely fully understood. Fundamental research into these mechanisms provides greater insight into the relationship between solution chemistry and mass spectra. Work herein addresses aspects of two ambient ionization mechanisms: electrospray ionization (ESI) and Direct Analysis in Real Time (DART). Ions produced by ESI are dispersed into a fine aerosol to encourage droplet evaporation, ultimately resulting in bare gaseous ions. Evaporation will induce cooling of emitted droplets over time. In this research, ratiometric fluorescence thermometry was used to probe droplet temperature evolution, and to assess whether it is adequate to impact probed equilibria. Under typical ESI conditions, droplet temperatures were observed to decrease ~30 K axially within ~0-5 mm from the emitter, before rewarming ~3 K over ~5 mm. These profiles were fit using diffusion- and surface-controlled evaporation models. Both fit well, (R ≥ 0.994), but the latter required unrealistic droplet radii for a good fit. In lateral profiles near the emitter tip, temperatures are lower in the periphery than on-axis (by ≤ 10 K), consistent with expected enrichment of the spray periphery with smaller droplets. At longer axial distances, lateral profiles were relatively flat. At lower flow rates, droplet temperature was observed to fall more rapidly, possibly attributable to changes in droplet size and/or velocity with flow rate. DART studies of selected compounds in a range of solvents were performed to assess gas-phase ion chemical effects on the relationship between detected ion abundances and bulk solution composition. When the DART gas stream contacts a sample solution, desorption/ionization of the matrix can inhibit analyte ionization, suppressing analyte signal. The effect depends on the components’ relative proton affinity and ionization energy. This effect was determined to be present with quantities ≥ 10 nL liquid or 10 μg [microgram] solid and at analyte-to-matrix ratios less than 1:100

Tetrahydrobiopterin analogues with NO-dependent pulmonary vasodilator properties

Reduced NO levels due to the deficiency of tetrahydrobiopterin (BH4) contribute to impaired vasodilation in pulmonary hypertension Due to the chemically unstable nature of BH4 it was hypothesised that oxidatively stable analogues of BR, would be able to support NO synthesis to improve Endothelial dysfunction in pulmonary hypertension Two analogues of BH4 namely 6-hydroxymethyl pterin (HMP) and 6-acetyl 7 7-dimethyl 7 8-dihydropterin (ADDP) were evaluated for vasodilator activity on precontracted rat pulmonary artery rings ADDP was administered to pulmonary hypertensive rats followed by measurement of pulmonary vascular resistance in perfused lungs and eNOS expression by immunohistochemistry ADDP and HMP caused significant relaxation in vitro in rat pulmonary arteries depleted of BH4 with a maximum relaxation at 0 3 mu M (both P<005) Vasodilator activity of ADDP and HMP was completely abolished following preincubation with the NO synthase inhibitor L-NAME ADDP and HMP did not alter relaxation induced by carbachol or spermine NONOate BH4 Itself did not produce relaxation In rats receiving ADDP 141 mg/kg/day pulmonary vasodilation induced by calcium ionophore A23187 was augmented and eNOS immunoreactivity was increased In conclusion ADDP and HMP are two analogues of BH4 which can act as oxidatively stable alternatives to BH4 in causing NO-mediated vasorelaxation Chronic treatment with ADDP resulted in Improvement of NO-mediated pulmonary artery dilation and enhanced expression of eNOS in the pulmonary vascular endothelium Chemically stable analogue, of BH4 may be able to limit endothelial dysfunction in the pulmonary vasculatur

Modification of chiral dimethyl tartrate through transesterification : immobilisation on POSS and enantioselectivity reversion in Sharpless asymmetric epoxidation

Modification of dimethyl tartrate has been investigated through transesterification with aminoalcohols to provide reactive functionalities for the covalent bonding of chiral tartrate to polyhedral oligomeric silsesquioxanes. The transesterification of dimethyl tartrate has been widely studied by means of using different catalytic systems and reaction conditions. Through the proper selection of both, the catalytic system and the reaction conditions, it is possible to achieve the mono- or the bis-substituted tartrate derivative as sole products. All the intermediate chiral tartrate-derived ligands were successfully used in the homogeneous enantioselective epoxidation of allylic alcohols providing moderate enantiomeric excess over the products. Attached amine groups have been used to support the modified tartrate ligands onto a haloaryl-functionalized silsesquioxane moiety. This final chiral tartrate ligand displays enantioselectivity reversion in the asymmetric epoxidation of allylic alcohols with regards to the starting dimethyl tartrate ligand, having both molecules them the same chiral sign. However, the POSS-containing ligand can be easily recovered in almost quantitative yield and reused in asymmetric epoxidation reactions. In addition, recovered silsesquioxane-pendant ligand, though displaying decreasing catalytic activity in recycling epoxidation tests, showed very stable enantioselective behavior