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1,2,3-Triisopropylguanidine [(Pr i NH) 2 CNPr i ], reacts with antimony tris(dimethylamide) [Sb(NMe 2 ) 3 ] to provide [Sb{(Pr i N) 2 CNHPr i }{(Pr i N) 2 CNPr i }] 1, a heavily distorted trigonal-bipyramidal complex in which the Sb is chelated by a [C(NPr i ) 3 ] 2- dianion and a [(Pr i N) 2 CNHPr i ] - monoanion; in the solid state the complexes form helices by N–H···N hydrogen bonding of the single proton.

Treatment of dimethylmagnesium with bulky alpha-diimine ligands provides either the biradical methyl-bridged complexes [(alpha-diimine-.)Mg+(mu-CH3)]2 via single electron transfer (SET), or the product of methyl transfer to an imine carbon atom depending upon conditions.

Dilithio-1,2,3-triphenylguanidide, [{(PhN)3C}Li2], reacts with [Cd{N(SiMe3)2}] to give [{(Me3Si)2N}2Cd{(PhN)3}Li2·3thf] 1; a novel co-complex containing three different metal coordination environments.

The new organometallic pentaruthenium cluster Ru5C(CO)13(η4-C4Ph4) has been prepared from the redox mediated ligand transfer reaction between [Ru5C(CO)14]2– and [Pd(η4-C4Ph4)(acetone)3]2+ during which the four-membered ring transfers from the palladium cation to a cluster ruthenium atom; the cluster has been characterised by single-crystal X-ray diffraction.

Two isomers of a benzene-coordinated pentaruthenium–carbido cluster, [Ru5C(CO)12(µ3 : η2 : η2:η2-C6H6)]1 and [Ru5C(CO)12(η6-C6H6)]2 have been synthesised from [Ru5C(CO)15]3 and structurally characterised by single crystal X-ray diffraction; 1 is irreversibly converted to 2 on mild thermolysis.

The bis-arene cluster complex [Ru6C(CO)11(η6-C6H3Me3-1,3,5)2]1 has been synthesised and characterized by single-crystal X-ray diffraction; it possesses a unique structure in which the octahedral cluster core is sandwiched between the two arenes.

Thermolysis of [Ru3(CO)12] in ethanol yielded the decanuclear hydridoruthenium cluster dianion [Ru10H2(CO)25]2–1. When a mixture of methanol and water is employed as thermolysis solvent the undecaruthenium hydridoruthenium trianion [Ru11H(CO)27]3–2 is also formed. Crystal structure analysis of 1 as its [N(PPh3)2]+ salt and 2 as its [NEt3(CH2Ph)]+ salt showed their metal core structures to be related, 2 being a square-faced capped congener of 1. Cluster 2 was alternatively formed in near-quantitative yields when [Ru3(CO)12] was thermolysed in acetonitrile containing traces of water for several days. It was not possible to locate the hydride ligands in the structures by potential-energy-minimisation calculations, but strong signals were seen in the 1H NMR spectra at δ–14.2 (s, 2 H) for 1 and at –5.47 (s, 1 H) for 2. On treatment of 1 and 2 with [Au(PPh3)Cl] in the presence of TlPF6, 1 showed no reactivity, but 2 reacted smoothly adding one [Au(PPh3)]+ moiety and giving a product characterised as [Ru11H(CO)27{Au(PPh3)}]2–3. The structural relationships between the known high-nuclearity ruthenium hydrido carbonyl clusters are discussed, and their implications for a possible cluster build-up sequence considered.

The dilithiation of N,N′,N″-triphenylguanidine with n-butyllithium in tetrahydrofuran provides the first example of a triazatrimethylenemethane system [C(NPh)3]2–, isoelectronic with both [C(CH2)3]2– and [CO3]2–; the X-ray crystal structure of the dilithium salt shows it to exist as a dimer with planar CN3 structural units.

The cluster trianion [Ru11H(CO)27]3– has been obtained from the thermolysis of [Ru3(CO)12] in a methanol–water mixture; an X-ray structure analysis of the [NEt3(CH2Ph)]+ salt shows that the metal core in the anion is a fragment of hexagonal close packing, which may be described alternatively as the condensation between two octahedra and two trigonal bipyramids sharing common triangular faces.

The cluster dianion [H2Ru10(CO)25]2–1 may be synthesised by redox condensation of the anion [HRu6(CO)18]–2 with [Ru3(CO)12]3 or by thermolysis of 3 in ethanol; it is the first high nuclearity ruthenium cluster not to contain an interstitial carbido-atom, and X-ray structure analysis shows that the cluster exhibits a unique metal core geometry which is clearly a fragment of the hexagonal close pack (hcp) system of metal atom packing.

The subcutaneous implantation of a cotton pellet into a rat results in the formation of a granuloma at the site of the implant. The early events comprise an accumulation of fluid and proteinaceous material together with an infiltration of neutrophils. The granuloma formed by day 7 is characterized by the formation of a vascularized fibrous capsule containing fibroblasts and infiltrating mononuclear cells which are rich in N- acetyl -β- d -glucosaminidase (NAG). Granuloma development was quantitated by dry weight measurements, and its cellular content was measured by assaying activity of NAG and total nucleic acid content. Nucleic acid determinations showed that cell infiltration into the granuloma took place at a virtually constant rate over a 7-day period. In contrast, the NAG activity did not change significantly until after day 5 when a large increase in the amount of enzyme extractable from the granuloma was seen. Systemic treatment of the animal with dexamethasone or indomethacin resulted in an inhibition of granuloma weight gain, NAG activity and nucleic acid levels. The data suggest that the two drugs acted during the early phase of granuloma development at the level of cell infiltration. Both drugs given on days 0–3 alone suppressed granuloma formation, whereas treatment on days 4–7 was without effect.

The reverse passive Arthus reaction in rat skin was quantitated by using increase in wet weight as a measure of edema and extractable myeloperoxidase as a measure of the intensity of polymorphonuclear leukocyte (PMN) infiltration. Treatment of the animal with dexamethasone prior to challenge with antigen/antibody resulted in an inhibition of both edema and the infiltration of inflammatory cells. In contrast, the non-steroidal anti-inflammatory drugs inhibited the intensity of cell infiltration (PMNs but not mononuclear cells) without affecting edema. The results are discussed in the light of the effects of these drugs on arachidonic acid oxidation.

X-ray structural studies of new thermolysis products from the reaction of Ru 3 (CO) 12 in heptane in the presence of 1,3,5-trimethylbenzene (mesitylene) confirm that they are the decaruthenium carbido-cluster dianion [Ru 10 C(CO) 24 ] 2− (I) and the hydrido decaruthenium carbido-cluster monoanion [HRu 10 C(CO) 24 ] − (II). Both anions have the giant tetrahedron Ru 10 metal framework, and the monohydride provides the first example of a hydrido ligand in a tetrahedral Ru 4 cavity.

A new class of tricyclic arylacetic acids was synthesized and evaluated as antiinflammatory/analgesic agents as well as inhibitors of prostaglandin synthetase. 11H-Dibenzo[b,e][1,4]dioxepin-2-, -3, -7, and -8-acetic and alpha-methylacetic acids and their derivatives were prepared by cyclization of diaryl ether precursors or by condensation of catechol and an aryl dihalide. The most potent compound in the carrageenan foot edema assay was alpha-methyl-11H-dibenzo[b,e][1,4]dioxepin-8-acetic acid (1 mg/kg = 43% inhibition). The most potent enzyme inhibitors were the 2-acetic acid and the alpha-methyl-7-acetic acid (IC50 = 0.1 microM). Some of these compounds were also found to be highly ulcerogenic.

Variants resistant to 2-deoxy-D-glucose have been isolated from a clonal line of pig kidney cells by serial cultivation in the presence of inhibitor. Hexokinase activity may be affected directly in this system, since the oxidation of glucose to 6-phosphogluconate by extracts from sensitive and resistant cells is blocked by the addition of 2-deoxy-glucose to the reaction mixture. This blockage was removed by the addition of glucose-6-phosphate to the system, but not by ATP. Resistant cells were found to accumulate significantly less 2-deoxyglucose-6-phosphate than sensitive cells. The rate of phosphorylation of 2-deoxyglucose, however, was higher in extracts from the resistant line. Alkaline phosphatase does not account for the reduced level of 2-deoxyglucose-6-phosphate since this enzyme is not detectable in sensitive or resistant pig kidney cells. Increased acid phosphatase activity was observed in resistant cells, but extracts with high acid phosphatase activity proved incapable of hydrolyzing either 2-deoxyglucose-6-phosphate or glucose-6-phosphate. In comparative growth studies, cells resistant to 2-deoxyglucose proliferated more extensively than sensitive cells in a low glucose nutrient. They removed glucose more effectively from this medium, and were less stimulated by the addition of intermediates from the tricarboxylic acid cycle. The evidence suggests that resistance to 2-deoxyglucose in the cells under study may be based on the ability of the resistant cells to proliferate at concentrations of glucose too low to support the growth of sensitive cells.

SUMMARY.— The amount of 14CO2 produced from carbon-14-labelled glucose by cultures of adult mouse skin has been measured. By comparing the recovery of radioactivity in 14CO2 using glucose-1-14C as a substrate with the recovery of activity in 14CO2 using glucose-6-14C as substrate, an estimation of the amount of glucose oxidized through the Krebs cycle and the pentose phosphate shunt was made. Approximately 1–6% of the glucose used was oxidized via the Krebs cycle, whereas 3–5–40% of the glucose passed through the pentose phosphate cycle. The addition of phenazine methosulphate (PMS) to the culture medium increased the 14CO2 output by mouse skin cultures by over 100%. Although PMS increased the rate at which glucose was oxidized through the Krebs cycle the greatest effect was on the pentose phosphate shunt, increasing the amount of glucose metabolized by this pathway to 30% of the total. Treatment of cultures with PMS was found to inhibit lipid synthesis almost completely.

The heterometallic dianion [Ru18Hg3(C)2(CO)42]2– has been obtained from the decanuclear ruthenium carbido-dianion [Ru10C(CO)24]2– as its [N(PPh3)2]+ salt by reaction with mercury(II) trifluoroacetate, and has been shown by X-ray single crystal analysis to be a dimer of two tricapped octahedral Ru9 cluster fragments, linked by a bridging Hg3 triangular unit.

Thermolysis of [Ru3(CO)12](1) in hydrocarbons heated under reflux containing excess of 1,3,5-trimethylbenzene(mesitylene) has yielded [Ru6C(CO)14(η6-C6H3Me3)](2a) and two new hexaruthenium compounds [Ru6(η2-µ4-CO)2(CO)13(η6-C6H3Me3)](3) and [HRu6(η2-µ4-CO)(CO)13(η7-µ2-C6H3Me2CH2)](4), shown by X-ray structure analyses to have metal frameworks previously unknown in ruthenium cluster chemistry; on further thermolysis the cluster (3) gives (2a) and is therefore the first intermediate in the well established conversion of triruthenium to hexaruthenium carbido-clusters to be identified.

Arachidonic acid oxygenation products were for many years held to be syn­ onymous with prostaglandins, but more recently they have been shown to include thromboxane A2 and a multitude of lipoxygenase pathway products, most notably the leukotrienes. In their review of inflammatory mediators in the first volume of this series, Larsen & Henson (1) provided a broad per­ spective on how prostaglandins and leukotrienes play a central, often syner­ gistic role with other mediators, both in the expression of the efferent limb of immune-based inflammatory responses and in acute inflammatory responses where specific immunity does not have a primary role. Prostaglandins and leukotrienes are produced by most, if not all cells, par­ ticipating in the afferent and efferent limbs of the immune system during host defense and inflammatory responses. Their formation depends on the deacy­ lation of arachidonic acid from cellular phospholipids catalyzed by the activity

A new class of tricyclic arylacetic acids was synthesized and evaluated as antiinflammatory/analgesic agents as well as inhibitors of prostaglandin synthetase. 11H-Dibenzo[b,e][1,4]dioxepin-2-, -3, -7, and -8-acetic and alpha-methylacetic acids and their derivatives were prepared by cyclization of diaryl ether precursors or by condensation of catechol and an aryl dihalide. The most potent compound in the carrageenan foot edema assay was alpha-methyl-11H-dibenzo[b,e][1,4]dioxepin-8-acetic acid (1 mg/kg = 43% inhibition). The most potent enzyme inhibitors were the 2-acetic acid and the alpha-methyl-7-acetic acid (IC50 = 0.1 microM). Some of these compounds were also found to be highly ulcerogenic.

The subcutaneous implantation of a cotton pellet into the rat results in the formation of a granuloma at the site of the implant. The early events comprise an accumulation of fluid and proteinaceous material together with an infiltration of neutrophils. The granuloma formed by day 7 is characterized by the formation of a vascularized fibrous capsule containing fibroblasts, giant cells and infiltrating mononuclear cells. Granuloma development was quantitated by dry weight measurements and its cellular content measured by assaying activity of N-acetyl-B-D-glucosaminidase (NAG) and total nucleic acid content. Nucleic acid determinations and histological examination show that cell infiltration into the granuloma takes place at a virtually constant rate over a 7 day period. In contrast the NAG activity does not change significantly until after day 5 when a large increase in the amount of enzyme extractable from the granuloma is seen. Systemic treatment of the animal with dexamethasone or indomethacin results in an inhibition of granuloma weight gain, NAG activity and nucleic acid levels. Drug treatment on days 0–3 results in suppression of granuloma formation whereas treatment on days 4–7 is without affect. This suggests that the two drugs are acting during the early phases of granuloma development. Histological examination shows clear differences between the action of dexamethasone and indomethacin.

Homogenates of rat skeletal muscle yield on centrifugation a particulate fraction containing relatively large vesicles capable of calcium uptake and a second fraction of smaller vesicles devoid of this capacity. Presumably the vesicles are derived from the sarcoplasmic reticulum. The glycogen synthase, adenyl cyclase, and phospho-diesterase specific activities are similar in both fractions, while in fractions of muscle from diabetic rats there are increased adenyl cyclase specific activities compared to muscle from normal rats. These results are in accord with the hypothesis that insulin acts upon the sarcotubular system of muscle.

Tissue selectivity of lovastatin, simvastatin and pravastatin was determined in male rats. Peak levels of active drug were found in all tissues examined between 0.5 and 2 hours after oral administration. The area under the curve describing 24 hour exposure of the tissues to drug indicated that the drugs were preferentially concentrated in the liver. However, the concentration of pravastatin was approximately 50% that of either lovastatin or simvastatin in the liver and 3-6 times higher in peripheral tissues. These studies demonstrate that the hydrophobic prodrugs, lovastatin and simvastatin show greater selectivity than the hydrophilic agent pravastatin towards the liver which is the target organ for inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.

Publisher Summary This chapter describes the methods used for elicitation of the reverse passive Arthus phenomenon in rat skin. The Arthus reaction is an inflammatory response resulting from the deposition of immune complexes within tissues. Tissue damage occurs due to the activation of components of the complement system, the infiltration of polymorphonuclear leukocytes (PMNs), and the release of lysosomal enzymes together with an increase in vascular permeability generated by the local release of mediators, and, in extreme cases, hemorrhages resulting from damage to the vessel wall. A study of the inflammatory response and the mechanism of tissue damage occurring in the Arthus phenomenon would therefore seem to have some relevance to the events occurring in a variety of pathological situations such as rheumatoid arthritis, glomerular nephritis, and systemic lupus erythematosus where immune complexes are deposited. The Arthus reaction can be elicited in a variety of animal species, rat, rabbit, and guinea pig being perhaps the most common, and in a number of different tissues including skin, the pleural space, synovial joints, and the paw. The Arthus reaction is elicited as a reverse passive phenomenon in which the antibody is injected at the reaction site and the antigen is introduced intravenously.

Publisher Summary This chapter discusses sponge implants as models. The inflammatory process is a response to tissue injury involving the infiltration of cells, the accumulation of fluids, the production of mediators, and the release of hydrolytic enzymes, all of which take place in a sequential and well-ordered series of events. To study this phenomenon in the tissues of the whole animal is a very desirable but extremely complicated procedure. Tissue fluids are not always accessible for biochemical examination, and the cellular infiltration is most commonly assessed by time consuming histologic methods. The techniques of sponge implantation described in this chapter represent a convenient system for providing ready access to the cells and fluids of an ongoing inflammatory response. Using these techniques, it has been shown that indomethacin reduces leukocyte migration into subcutaneously implanted sponges but that this effect was distinct from the effect of indomethacin in reducing the content of prostaglandin in the exudate.

Ionic coupling between the dianionic ruthenium cluster [Ru 5 C(CO 14 ] 2− and the dicationic rhodium species [Rh(C 5 Me 5 )MeCN) 3 ] 2+ in refluxing CH 2 Cl 2 yields the hexanuclear mixed metal carbido cluster Ru 5 RhC(CO) 14 (η 5 -C 5 Me 5 ) ( 1 ). Activation of ( 1 ) towards reaction with C 5 H 6 or C 6 H 8 by trimethylamine- N -oxide (Me 3 NO) results in the formation of Ru 5 RhC (CO) 9 (η 5 -C 5 Me 5 )(η 5 C 5 H 5 ) 2 ( 2 ) and Ru 5 RhC(CO) 11 (η 5 -C 5 Me 5 (μ 3 -η 2 :η 2 :η 2 -C 6 H 6 ) 3 respectively. Complexes 1 and 2 have been structurally characterized by X-ray diffraction.

Reaction of the square-pyramidal cluster [Ru5C(CO)15]1 with cyclohexa-1,3-diene and Me3NO in CH2Cl2 at ambient temperature affords the novel species [Ru5C(CO)13(µ-η2:η2-C6H8)]2 which has been fully characterized by X-ray diffraction studies [monoclinic, space group P21/n, a= 16.193(3), b= 9.897(2), c= 19.536(4)A, β= 98.80(3)° and Z= 4]. Further reaction of compound 2 with Me3NO in the same solvent results in the dehydrogenation of the C6H8 ligand and the production of two isomers 3a and 3b of the benzene derivative [Ru5C(CO)12(C6H6)]. In agreement with mass spectroscopic and 1H NMR data, the X-ray diffraction analysis shows that the benzene ligand is bound in a face-capping mode in [Ru5C(CO)12(µ3-η2:η2:η2-C6H6)]3a and in a terminal mode in [Ru5C(CO)12(η6-C6H6)]3b, respectively. Compound 3a is triclinic, space group P1–, a= 9.525(2), b= 14.574(3), c= 9.484(4)A, α= 96.29(2), β= 112.37(3), γ= 82.33(2)° and Z= 2; 3b is monoclinic, space group P21/c, a= 15.26 (2), b= 16.675(9), c= 19.016(9)A, β= 96.04(7)° and Z= 8. On heating 3a in hexane a quantitative and irreversible conversion to 3b is observed. Treatment of 3b with carbon monoxide produces the adduct [Ru5C(CO)13(η6-C6H6)]4a, which, on the basis of a single crystal X-ray diffraction study, has been shown to contain a ‘bridged-butterfly’ arrangement of five ruthenium atoms. Compound 4a is monoclinic, space group P21/n, a= 9.792(4), b= 15.718(2), c= 16.446(3)A, β= 96.37(2)° and Z= 4. On standing in CH2Cl2, 4a undergoes loss of carbon monoxide to give the apical isomer [Ru5C(CO)12(C6H6)]3c. On heating in hexane over a prolonged period 3c undergoes quantitative isomerization to 3b.

The synthesis, chemical characterisation and single crystal X-ray structural study of the bis-toluene hexaruthenium carbidocarbonyl cluster [Ru 6 C(CO) 11 (η 6 C 6 H 5 Me)(μ 3 -η 2 : η 2 : η 2 -C 6 H 5 Me)] is reported. A variable temperature 1 H n.m.r. study reveals that in solution the complex exists in two isomeric forms, one of them, that observed in the solid state and the other the trans -[Ru 6 C(CO) 11 ](η 6 -C 6 H 5 Me) 2 ] isomer. Interchange of the toluene ligand between the μ 3 -η 2 : η 2 : η 2 and η 6 co-ordination mode if confirmed by deuterum labelling experiments involving C 6 D 5 CD 3 .

Light is transmitted along the central core of an optical fiber by total internal reflection at the interface with the surrounding layer. Here, we describe a method by which the optical properties of a cross-sectioned fibre can be studied by means of the luminescent image in the scanning electron microscope (SEM).The sample is prepared by depositing a thin cathodoluminescent layer over the end of a broken or cross-sectioned optical fiber. A thin conducting layer is then deposited to prevent charging. The far end of the fiber is optically coupled to a photomultiplier. During examination in the SEM, the sample is scanned by a fine electron beam, which gives a localised source of light on the surface of the sample at the point of impact of the beam. The quantity of light that is transmitted along the fiber to the photomultiplier determines the brightness of that particular pixel in the recorded image.

Cluster molecules, HRu10C(CO)24–, are characterised by interstitial hydride ligands down to 250 K, but below that temperature, progressively more and more molecules acquire externally-bound hydrogens.