Synthesis and structure-activity relationship of the isoindolinyl benzisoxazolpiperidines as potent,selective, and orally active human dopamine D4 receptor antagonists

A new class of potent dopamine D(4) antagonists was discovered with selectivity over dopamine D(2) and the alpha-1 adrenoceptor. The lead compound was discovered by screening our compound collection. The structure-activity relationships of substituted isoindoline rings and the chirality about the hydroxymethyl side chain were explored. The isoindoline analogues showed modest differences in potency and selectivity. The S enantiomer proved to be the more potent enantiomer at the D(4) receptor. Several analogues with greater than 100-fold selectivity for D(4) over D(2) and the alpha-1 adrenoreceptor were discovered. Several selective analogues were active in vivo upon oral or intraperitoneal administration. A chiral synthesis starting from either D- or L-O-benzylserine is also described.     

Binding of cadmium,copper, and zinc to humic substances originating from municipal solid waste compost

The application of municipal solid waste (MSW) compost increases both the trace metal loading and the organic matter in the soil. To characterize the quality and metal-binding capacity of the compost OM, we extracted humic acid (HA) and fulvic acid (FA) from mature MSW compost and analyzed them for elemental composition, acid-titratable functional groups, total metal content, and structural components (by ¹³C NMR). HA constituted 67% of all extracted humic substances and differed significantly from HAs of cultivated lands: The compost HA exhibited smaller molecular size, a higher N content, and lower aromaticity due to large amounts of saturated aliphatic components. Metal complexation studies of the extracted HA and FA were performed by equilibrium dialysis titration. The complexing capacity (CC) was highest for Cu: CC_HA = 3357 and CC_FA = 5221 μmol Cu g⁻¹ of dissolved organic carbon (DOC) at pH 5. Zn and Cd were bound (at pH 7) in smaller concentrations: CC_HA(Zn) = 2167, CC_FA(Zn) = 2809, CC_HA(Cd) = 2386, and CC_FA(Cd) = 2468 μmol metal g⁻¹ of DOC. Stability constants for binding on the strongest sites (pK_int) were determined as pK_intHA = 6.6 and pK_intFA = 7.3 for Cu at pH 5; and pK_intHA = 8.0 and pK_intFA = 6.4 for Cd at pH 7. Since these measured parameters fall within the ranges of values obtained for soil humic substances, we conclude that in soils with little organic matter, compost addition will significantly increase the amount of highly reactive organic complexing agents for trace metals in the soil.     

Advanced Alumina Composites Reinforced with Titanium-Based Alloys

New (inter)metallic-ceramic composites for high-temperature structural and functional applications are prepared via high-energy ball milling. During compaction by pressureless sintering, dense Al₂O₃/Ti-based alloy composites are formed that consist of inter-connected networks of the ceramic and the (inter)metallic phases. Ti-Al-V/Al₂O₃ and Ti-Al-Nb/Al₂O₃ composites show enhanced damage tolerance over monolithic Al₂O₃, i.e ., fracture toughnesses up to 5.6 MPa·m^0.5 and bending strengths up to 527 MPa. The resistance against abrasive wear is almost doubled with respect to monolithic Al₂O₃ ceramic. Electrical resistivity scales with the ceramic volume fraction and ranges between 0.3 mΩ·cm and 55.1 mΩ·cm, with only a weak temperature dependence ≤700°C.     

Biogenic versus abiogenic emissions from agriculture in the Netherlands and options for emission control in tomato cultivation

In this paper, present-day emissions of greenhouse gases and acidifying compounds from agriculture are analysed at the farm level. Quantitative estimates are given for these emissions from three nested systems in the Netherlands: the agricultural sector, greenhouse horticulture, and tomato cultivation under glass. Total emissions are subdivided into emissions from biogenic sources and abiogenic sources. We conclude that, although most of the emissions from the agricultural sector have biogenic sources, those from abiogenic sources should not be neglected. Abiogenic emissions are mainly from greenhouse horticulture. The cost-effectiveness of options to reduce carbon dioxide (CO₂) and nitrogen oxides (NO_x) emissions from on-farm combustion of natural gas in tomato cultivation under glass is analysed. An inventory is given of technical reduction options that are presently available in practice. Based on information about the costs and the reduction potential of each option, cost-efficiency curves are derived for both types of emissions. Relative to a situation where none of the described options were applied (early nineties), CO₂ and NO_x emissions from tomato cultivation can be reduced at most by about 70% and 75%, respectively, by combinations of technical options. This revised version was published online in August 2006 with corrections to the Cover Date.     

Esterification of glycerol with conjugated linoleic acid and long-chain fatty acids from fish oil

Free fatty acids from fish oil were prepared by saponification of menhaden oil. The resulting mixture of fatty acids contained ca. 15% eicosapentaenoic acid (EPA) and 10% docosahexaenoic acid (DHA), together with other saturated and monounsaturated fatty acids. Four commercial lipases (PS from Pseudomonas cepacia, G from Penicillium camemberti, L2 from Candida antarctica fraction B, and L9 from Mucor miehei) were tested for their ability to catalyze the esterification of glycerol with a mixture of free fatty acids derived from saponified menhaden oil, to which 20% (w/w) conjugated linoleic acid had been added. The mixtures were incubated at 40°C for 48h. The ultimate extent of the esterification reaction (60%) was similar for three of the four lipases studied. Lipase PS produced triacylglycerols at the fastest rate. Lipase G differed from the other three lipases in terms of effecting a much slower reaction rate. In addition, the rate of incorporation of omega-3 fatty acids when mediated by lipase G was slower than the rates of incorporation of other fatty acids present in the reaction mixture. With respect to fatty acid specificities, lipases PS and L9 showed appreciable discrimination against esterification of EPA and DHA, respectively, while lipase L2 exhibited similar activity for all fatty acids present in the reaction mixture. The positional distribution of the various fatty acids between the sn-1,3 and sn-2 positions on the glycerol backbone was also determined.     

Design and synthesis of foam glasses from recycled materials

Recycling has emerged as an environmental key point due to the diminishing of natural resources and the generation of ever-increasing amounts of industrial solid wastes. Glass wastes are among the materials that attract great interest in the recycling concept. This work presents the results of foams production from four series of compositions. The first series comprises powders of a sodium-calcium-silicate sheet glass cullet as the main component, an alkali-earth aluminosilicate glass as an additive, and a reagent grade silicon carbide (SiC) powder as gassing agent. In the second series, the glass cullet was used in combination with fly ashes (FLA) as main components, while SiC waste from abrasive paper served as foaming agent. In the third and fourth series, carbonates (calcite and dolomite) were used for foaming powder mixtures composed of sheet glass cullet and FLA, and powdered cathode ray tube panel glasses, respectively. All the processing parameters, including the main components, the nature and content of foaming agents are shown to play a crucial role on the foaming ability and final properties of the glass foams.     

Modeling the Electrical Conductive Paths within All-Solid-State Battery Electrodes

All-solid-state batteries constitute a very promising energy storage device. Two very important properties of these battery cells are the ionic and the electrical conductivity, which describe the ion and the electron transport through the electrodes, respectively. In this work, a numerical method is presented to model the electrical conductivity, considering the outcome of discrete-element method simulations and the intrinsic conductivities of both the active material particles and the conductive additive particles. The results are calibrated and validated with the help of experimental data of real manufactured electrodes. The tortuosity, which strongly influences the ionic conductivity, is also presented for the analyzed electrodes, taking their microstructure into account.