The desaturation and elongation of linolenic acid and eicosapentaenoic acid by hepatocytes and liver microsomes from rainbow trout (Oncorhynchus mykiss) fed diets containing fish oil or olive oil

The products of desaturation and elongation of [1−¹⁴C] 18:3(n − 3) and [1−¹⁴C]20:5(n − 3) were studied using hepatocytes and microsomes prepared from livers of trout maintained on diets containing either olive oil or fish oil, to establish the extent to which the formation of 22:6(n − 3) was enhanced in the absence of dietary 22:6(n − 3) and to investigate the pathway(s) of conversion of 18:3(n − 3) and 20:5(n − 3) to 22:6(n − 3). Levels of 20:5(n − 3) and 22:6(n − 3) in the total lipid of hepatocytes from trout fed olive oil were 20-fold and 10-fold, respectively, lower than in cells from trout fed fish oil. For both dietary groups, [1−¹⁴C]18:3(n − 3) was incorporated into hepatocyte lipid to a greater extent than [1−¹⁴C]20:5(n − 3). Almost 70% of the total radioactivity from [1−¹⁴C]18:3(n − 3) was recovered in hepatocyte triacylglycerols, whereas radioactivity from [1−¹⁴C]20:5(n − 3) was recovered almost equally in neutral lipids (52%) and polar lipids (48%). The products of desaturation and elongation from both labelled substrates were esterified mainly into hepatocyte polar lipids, whereas elongation products of [1−¹⁴C]18:3(n − 3) were preferentially incorporated into neutral lipids. Radioactivity recovered in the 22:6(n − 3) of polar lipids of hepatocytes from trout fed olive oil, from both ¹⁴C substrates, was approximately double that in hepatocytes from trout fed fish oil. No radioactivity from either [1−¹⁴C]18:3(n − 3) or [1−¹⁴C]20:5(n − 3) was incorporated into 22:6(n − 3) by microsomes isolated from livers from either group of fish and incubated in the presence of acetyl-CoA, malonyl-CoA, NADH, NADPH, ATP and coenzyme A. However, significant radioactivity was recovered in 24:5(n − 3) and 24:6(n − 3) from [1−¹⁴C]20:5(n − 3) and more radioactive 24:6(n − 3) accumulated in microsomes from trout fed olive oil than from trout fed fish oil. The results establish that the formation of 22:6(n − 3) from both 18:3(n − 3) and 20:5(n − 3) in hepatocytes of rainbow trout is stimulated by omitting 22:6(n − 3) from the diet and are consistent with the biosynthesis of 22:6(n − 3) in trout liver cells proceeding via 24:5(n − 3) and 24:6(n − 3) intermediates.     

The pathway from arachidonic to docosapentaenoic acid (20:4n-6 to 22:5n-6) and from eicosapentaenoic to docosahexaenoic acid (20:5n-3 to 22:6n-3) studied in testicular cells from immature rats

The concentration-dependent metabolism of 1-¹⁴C-labelled precursors of 22:5n-6 and 22:6n-3 was compared in rat testis cells. The amounts of [¹⁴C]22- and 24-carbon metabolites were measured by HPLC. The conversion of [1-¹⁴C]20:5n-3 to [3-¹⁴C]22:6n-3 was more efficient than that of [1-¹⁴C]20:4n-6 to [3-¹⁴C]22:5n-6. At low substrate concentration (4 μM) it was 3.4 times more efficient, reduced to 2.3 times at high substrate concentration (40 μM). The conversion of [1-¹⁴C]22:5n-3 to [1-¹⁴C]22:6n-3 was 1.7 times more efficient than that of [1-¹⁴C]22:4n-6 to [1-¹⁴C]22:5n-6 using a low, but almost equally efficient using a high substrate concentration. When unlabelled 20:5n-3 was added to a cell suspension incubated with [1-¹⁴C]20:4n-6 or unlabelled 22:5n-3 to a cell suspension incubated with [1-¹⁴C]22:4n-6, the unlabelled n-3 fatty acids strongly inhibited the conversion of [1-¹⁴C]20:4n-6 or [1-¹⁴C]22:4n-6 to [¹⁴C]22:5n-6. In the reciprocal experiment, unlabelled 20:4n-6 and 22:4n-6 only weakly inhibited the conversion of [1-¹⁴C]20:5n-3 and [1-¹⁴C]22:5n-3 to [¹⁴C]22:6n-3. The results indicate that if both n-6 and n-3 fatty acids are present, the n-3 fatty acids are preferred over the n-6 fatty acids in the elongation from 20- to 22- and from 22- to 24-carbon atom fatty acids. In vivo the demand for 22-carbon fatty acids for spermatogenesis in the rat may exceed the supply of n-3 precursors and thus facilitate the formation of 22:5n-6 from the more abundant n-6 precursors.     

Mechanisms for acceleration of halide anation reactions of platinum(IV) complexes. REOA versus ligand assistance and platinum(II) catalysis Without central ion exchange

Chloride anation of trans-Pt(CN)₄ClOH₂⁻ has been studied with and without Pt(CN)₄²⁻ present at 25.0°C by use of stopped-flow and conventional spectrophotometry and a 1.00 M perchlorate medium. The rate law in the absence of Pt(CN)₄²⁻ is Rate=(p₁ + p₂ [H⁺] ) [Cl⁻]² [complex]/(1 + q [Cl₋]) with p₁=(3.0 ± 0.1) × 10⁻⁵ M⁻²s⁻¹, p₂=(3.6 ± 0.1) × 10⁻⁵ M⁻³ s⁻¹ and q=(0.62 ± 0.02) M⁻¹. It is compatible with a chloride assistance via an intermediate of the type Cl-Cl-Pt(CN)₄···OH₂²⁻, in which the reactivity of the aqua ligand is enhanced due to a partial reduction of the platinum. This mechanism of halide assistance is in principle the same as the modified reductive elimination oxidative addition (REOA) mechanism proposed by Poë, in which the intermediate is not split into free halogen, platinum(II) and water, and in which electron transfer not necessarily involves complete reduction to platinum(II). To avoid confusion with complete reductive eliminations, reactions without split of the intermediates are here termed halide-assisted reactions. The pH-dependence indicates acid catalysis via a protonated intermediate ClClPt(CN)₄···OH₃⁻.The Pt(CN)₄²⁻accelerated path has the rate law Rate=

[Cl-] [Pt(CN)₄²⁻] [complex] where k=(39.9±0.5) M⁻² s⁻¹ and K_a=(4.0±0.2)10⁻² M is the protolysis constant of trans-Pt(CN)₄ClOH²⁻.Reaction between PtCl₅OH₂⁻ and chloride is accelerated by Pt(CN)₄²⁻ and gives PtCl₆²⁻ as the reaction product. The rate law is Rate=k [Cl⁻] [Pt(CN)₄²⁻] [PtCl₅OH₂⁻] with k=(5.6 ± 0.2)10⁻³ M⁻² s⁻¹ at 35.0°C and for a 1.50 M perchlorate acid medium. The reaction takes place without central ion exchange. Alternative mechanisms with two consecutive central ion exchanges can be excluded. The role of Pt(CN)₄²⁻ in this reaction is very similar to that of the assisting halide in the halide assisted anations. [p ]Reaction between trans-Pt(CN)₄ClOH₂⁻ and PtCl₄²⁻ gives Pt(CN)₄²⁻ and PtCl₅OH₂⁻ as products and has the rate law Rate=k[PtCl₄²⁻] [trans-Pt(CN)₄ClOH₂⁻] with k=(3.32 ± 0.02) M⁻¹ s⁻¹ at 25 °C for a 1.00 M perchloric acid medium. The formation of an aqua complex as the primary reaction product and the rate independent of [Cl⁻] shows that formation of a bridged intermediate of the type Pt(II)Cl₄ClPt(IV)(CN)₄OH₂³⁻ is formed in the initial reaction step, not five-coordinated PtCl₅³⁻.     

Hydroperoxides produced by n −6 lipoxygenation of arachidonic and linoleic acids potentiate synthesis of prostacyclin related compounds

In a previous paper we reported that arachidonic acid (20:4(n − 6)) strongly enhances the endothelial cell synthesis of prostaglandin I₃ (PGI₃) from eicosapentaenoic acid (20:5(n − 3)), in stimulating the cyclooxygenase rather than the prostacyclin synthase (Bordet et al. (1986) Biochem. Biophys. Res. Commun. 135, 403–410). In the present study, endothelial cell monolayers were co-incubated with exogenous 20:5(n − 3) or docosatetraenoic acid (22:4(n − 6)), and n − 6 lipoxygenase products of 20:4(n − 6) or linoleic acid (18:2(n − 6)), namely 15-HPETE and 13-HPOD, respectively. Prostaglandins or dihomoprostaglandins were then measured by gas chromatography-mass spectrometry. Both hydroperoxides, up to 20 μM, stimulated the cyclooxygenation of 20:5(n − 3) and 22:4(n − 6), in particular the formation of PGI₃ and dihomo-PGI₃, respectively. Higher concentrations inhibited prostacyclin synthase. In contrast, the reduced products of hydroperoxides, 15-HETE and 13-HOD, failed to stimulate these cyclooxygenations, 13-HPOD appeared more potent than 15-HPETE and the cyclooxygenation of 22:4(n − 6) seemed to require higher amounts of hydroperoxides to be efficiently metabolized than 20:5(n − 3). These data suggest that prostacyclin potential of endothelium might be enhanced by raising the peroxide tone.     

Kinetics and mechanism of the reaction between 1,2-diaminopropanetetra-acetatoferrate(III) and cyanide ion

The present study examines the kinetics and mechanism of the system [FePDTA(OH)]²⁻ + 5CN⁻ ⇌ [Fe(CN)₅OH]³⁻ + PDTA⁴⁻ at pH= 11.0±0.02, I= 0.25 M and temperature = 25 ± 0.1 °C. The reaction has been studied spectrophotometrically at 395 nm (λ_max of [Fe(CN)₅OH]³⁻). The data show that the reaction has three distinguishable stages; the first stage is formation of [Fe(CN)₅OH]³⁻, the second is conversion of [Fe(CN)₅OH)]³⁻ to [Fe(CN)₆]³⁻ and last is reduction of [Fe(CN)₆]³⁻ to [Fe(CN)₆]³⁻ by the released ligand, viz., PDTA. The first reaction shows variable order dependence on cyanide concentration, one at high cyanide concentration and two at low cyanide concentration. The second reaction exhibits first order dependence on the concentration of [Fe(CN)₅OH]³⁻ as well as cyanide. The reverse reaction between [Fe(CN)₅OH]³⁻ and PDTA is first order in [Fe(CN)₅OH]³⁻ and PDTA, and inverse first order in cyanide. On the basis of forward and reverse rate studies, a five-step mechanism has been proposed for the first reaction.     

Temperature and pressure dependent equilibrium studies of 1, 4, 8, 11-tetramethyl-1, 4, 8, 11-tetraazacyclotetradecane nickel(ii) in coordinating solvents

In coordinating solvents, the complex 1, 4, 8, 11- tetramethyl-1, 4, 8, 11-tetraazacyclotetradecane nickel(II) bisperchlorate exists as an equilibrium mixture involving four coordinate R,S,R,S-[Ni(tmc)]²⁺ and five coordinate R,S,R,S-[Ni(tmc)(solvent)]²⁺ species. Spectrophotometric measurements of this equilibrium in a number of solvents have been conducted over a range of temperatures and pressures. The stability order for the five coordinate complex in the solvents investigated is CH₃CN>DMF>DMSO>C₆H₅CN> H₂O>ClCH₂CN at 25 °C. Differences in stability are considered in terms of the measured thermodynamic parameters ΔH° and ΔS°. Both steric and electronic factors were found to influence solvent coordination with the macrocyclic complex.For the equilibrium in CH₃CN, C₆H₅CN, DMF and H₂O, reaction volumes, ΔV°, of −3.2±0.5, −4.2±0.5, −0.2±0.5 and −0.5±0.5 cm³ mol⁻¹ respectively have been determined. Each is significantly smaller than the corresponding solvent molar volume. The ΔV° for the equilibrium in CH₃CN is comparable with the previously determined activation volume for exchange of this solvent on R, S, R, S- [Ni(tmc)(CH₃CN)]²⁺. The equilibrium and measured volume parameters are discussed in relation to the mechanism for solvent exchange.     

Tin-119 NMR Studies on adduct formation and stereochemistry of organoyltin(IV)trihalides

qazTin-119 and phosphorus-31 NMR spectra have been recorded for a series of adducts of RSnX₃ (R  Me, Ph; X  Cl, Br) with halide, tributylphosphine (P) and tributylphosphine oxide (L). The adducts were either 1:1 five coordinate or 1:2 six coordinate complexes. The tin-ll9 NMR spectra of mixtures of corresponding chloro and bromo complexes reveal, in most cases, all possible mixed halide species but much additional structural information is obtained from these spectra which could not be extracted from the spectra of individual compounds themselves. Thus in some cases, in the five coordinate species the Berry pseudorotation between isomers within a particular stoichiometry could be slowed on the NMR timescale which allowed a determination of the molecular structure. An equimolar mixture of [PhSnCl₅]²⁻ and [PhSnBr₅]²⁻ shows eleven of the twelve geometries possible for [PhSnCl_xBr_5−x]²⁻. In the six coordinate series [RSnX₄P]⁻ the tin-119 NMR spectra of the mixtures of [RSnCl₄P]⁻ and [RSnBr₄P]⁻ allow the geometry to be determined as trans. Application of the pairwise additivity model for calculation of the tin-119 chemical shift positions for the mixed halide systems are discussed.     

Metabolism of 7,10,13,16-docosatetraenoic to dihomo-thromboxane 14-hydroxy-7,10,12-nonadecatrienoic acid hydroxy fatty acids by human platelets

Human platelets metabolize 7,10,13,16-docosatetraenoic acid (22:4(n−6) into dihomo-thromboxane B₂ and 14-hydroxy-7,10,12-nonadecatrienoic acid at about twenty percent of the rate they convert arachidonic to thromboxane B₂ and 12-hydroxy-5,8,10-heptadecatrienoic acid. 14-Hydroxy-7,10,12,16-docasatetraenoic was the major metabolite produce via the lipoxygenase pathway. Several other hydroxy were also produced in small amounts via an indomethacin-insensitive pathway. Incubation of 20 μM arachidonic acid with various levels of 22:4(n−6) resulted In a dose-dependent inhibition of both thromboxane B₂ and 12-hydroxy-5,8,10-heptadecatrienoic acid production. Coversely, 12-hydroxy-5,8,10,14-eicosatetraenoic acid synthesis was stimulated because of substrate shunting to the lipoxygenase pathway. These results show that 22:4(n−6) may modify platelet function both by serving as a precursor for a 22-carbon thromboxane and by suppressing the synthesis of thromboxane A₂ from arachidonic acid. In addition, our results suggest that simultaneous release of 22:4(n−6) and arachidonic acid from platelet phospholipids will result in an elevation of both 12-hydroxy-5,8,10,14-eicosatetraenoic acid levels as well as simultaneous synthesis of 14-hydroxy-7,10,12,16-docosatetraenoic acid.     

Spectroscopic and reactivity comparison of pentacyanonitrosylruthenate(2-) with pentacyanonitrosylferrate(2-), nitroprusside

Lithium penta(cyano-¹³C)nitrosylruthenate (2-), Li₂[Ru(¹³CN)₅NO], in which the anion is the ruthenium analogue of the nitroprusside ion, has been synthesized at 90% isotopic enrichment, and characterized spectroscopically. Despite the very high level of ¹³C enrichment, no two-bond coupling ²J(¹³C_ax-Ru¹³C_eq) was detected in the high-frequency ¹³C NMR spectrum of Li₂[Ru(¹³CN)₅NO], nor was any such coupling observed in Li₄[Ru(¹³CN)₅(¹⁵NO₂)] although both two-bond couplings to ¹⁵N, ²J(¹³C_ax-Ru¹⁵NO₂) and ²J(¹³C_eqRu¹⁵N) were observed. Li₂[Ru(¹³CN)₅(¹⁴NO)] reacted with excess of Li[¹⁵NO₂] to yield Li₄[Ru(¹³CN)₅(¹⁵NO₂)] only: no Li₂[Ru(¹³CN)₅(¹⁵NO)] was observed. Li₄[Ru(¹³CN)₅(¹⁴NO₂)] however showed no exchange with Li[¹⁵NO₂]. While [Ru(CN)₅NO]²⁻ reacted with both OH⁻ and SH⁻ in reactions similar to those of [Fe(CN)₅NO]²⁻, no reactions were detected between [Ru(CN)₅NO]²⁻ and piperidine, [CH(CN)₂]⁻, [CH(COCH₃)₂]⁻, MeS⁻, or [S₂O₄]²⁻, all of which are known to react readily with [Fe(CN)₅NO]²⁻     

Differential effects of unsaturated fatty acids on phospholipid synthesis in human leukemia monocytic U937 cells

The biosynthesis of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in monocyte-like leukemia U937 cells was monitored by adding [³H]choline, [¹⁴C]ethanolamine or [¹⁴C]glycerol to the culture media; incorporation into phospholipid (PL) increased with time. The effect of unsaturated fatty acids (UFA) on PC and PE synthesis was investigated by pretreating U937 cells for 72h with 10 μM 18:1 (n –9), 18:2 (n –6), 18:3 (n –3), 20:4 (n –6) and 20:5 (n –3). The UFA caused no alteration in cell growth, as evidenced by light microscopy and the incorporation of [³H]thymidine and [³H]leucine. Total cellular uptake of radioactive precursors remained unaffected by all the treatments. Pretreatment with 20:5 resulted in approximately 25 per cent reduction in the incorporation of [³H]choline into PL, while no significant effect was detected with the other UFAs. 18:3, 20:4 and 20:5 depressed the incorporation of [¹⁴C]ethanolamine into PL by 34 per cent, 28 per cent and 49 per cent respectively. However, there was no redistribution of label with any of the treatments. 18:3, 20:4 and 20:5 also antagonized the stimulatory effect of endotoxin (LPS) on PC and PE synthesis. In addition, the incorporation from [¹⁴C]glycerol into PC and PE was reduced by 18:3, 20:4 and 20:5. Although the PL composition of the cells remained essentially unaffected, our study shows that chronic treatment of U937 cells with n –3 PUFA (20:5) depressed PC and PE synthesis, and 18:3 and 20:4 also caused inhibition of PE synthesis.     

Synthesis, crystal structure, NMR and ab initio molecular-orbital studies of some magnesium(II) macrocyclic Schiff-base complexes, with two 2-aminoethyl pendant arms

Three new Mg(II) bis(pendant arm) macrocyclic Schiff-base complexes, [MgLⁿ]²⁺(n=5, 6, 7), have been prepared via cyclocondensation of 2,6-diacetylpyridine with branched hexaamines and characterised spectroscopically. In addition, for [MgL⁵](ClO₄)₂ the crystal structure is reported. This is the first X-ray structural determination of an Mg(II) complex coordinated by seven nitrogen atoms. The ligands, L, are 15-, 16- and 17-membered pentaaza macrocycles having two 2-aminoethyl pendant arms [L⁵; 2,13-dimethyl-6,9-bis(aminoethyl)-3,6,9,12,18-pentaazabicyclo[12.3.1]octadeca-1(18), 2, 12, 14, 16-pentaene, L⁶; 2,14-dimethyl-6,10-bis(aminoethyl)-3,6,10,13,19-pentaazabicyclo[13.3.1]nonadeca-1(19), 2, 13, 15, 17-pentaene and L⁷; 2,15-dimethyl-6,11-bis(aminoethyl)-3,6,11,14,20-pentaazabicyclo[14.3.1]eicosa-1(20),2,14,16,18-pentaene]. The crystal structure of [MgL⁵](ClO₄)₂, was determined by X-ray diffraction and showed that the complex cation that had formed consisted of a pentagonal bipyramidally coordinated Mg(II) ion. All complexes were characterised by IR, ¹H NMR,¹³C NMR, COSY(H,H) and HETCOR(H,C) spectroscopy, and the data indicate that the structure is approximately pentagonal bipyramidal in each case. This structural assignment is also supported by ab initio HF-MO calculations made using the standard 3-21G* basis set.     

Biosynthesis of Acyl Lipids Containing Very-Long Chain Fatty Acids in Microspore-Derived and Zygotic Embryos of Brassica napus L. cv Reston

Biosynthesis of very long chain (>C₁₈) fatty acids (VLCFAs) and the pathway for their incorporation into acyl lipids was studied in microspore-derived (MD) and zygotic embryos of Brassica napus L. cv Reston. In the presence of [1-¹⁴C]oleoyl-coenzyme A or [1-¹⁴C] eicosenoyl-coenzyme A, malonyl-coenzyme A, and reducing equivalents, maximal in vitro elongation activity was expressed in protein preparations from early-mid cotyledonary stage MD embryos (17-20 days in culture), when endogenous eicosenoic (20:1) and erucic (22:1) acids were just beginning to accumulate (approximately 1.5 milligrams per gram dry weight). The biosynthesis of VLCFAs and their incorporation into glycerolipids in vitro in the MD embryo system occurred at rates comparable to those measured in developing zygotic Reston embryos at about 20 days postanthesis. When glycerol-3-phosphate was supplied as acyl acceptor in time-course experiments using homogenates prepared from 18-day MD embryos, newly synthesized [¹⁴C]20:1 and [¹⁴C]22:1 were incorporated primarily into triacylglycerols (TAGs) and, to a lesser extent, into lyso-phosphatidic/phosphatidic acids, diacylglycerols, and phosphatidylcholines as well as the acyl-coenzyme A and free fatty acid pools. [¹⁴C]24:1 was not detected in any acyl lipid. Stereospecific analyses of the radiolabeled TAGs indicated that [¹⁴C]20:1 and [¹⁴C]22:1 moieties were esterified predominantly at the sn-3 position, but were also found at the sn-1 position. [¹⁴C]20:1, but not [¹⁴C]22:1, was detected at the sn-2 position. Similar patterns of ¹⁴C-labeled VLCFA distribution were obtained in experiments conducted using a 15,000g pellet fraction from 18-day MD embryos. All trends observed in the formation of TAGs containing VLCFAs in the Reston MD embryo system were also confirmed in studies of zygotic embryos of the same cultivar. The data support the biosynthesis of 20:1 and then 22:1 via successive condensations of malonyl-coenzyme A with oleoyl-coenzyme A and, for the first time in B. napus, demonstrate the incorporation of newly synthesized VLCFAs into TAGs via the Kennedy pathway.     

No relationship between morphology changes and metabolism of α-linolenate and eicosapentaenoate in rainbow trout (Oncorhynchus mykiss) astroglial cells in primary culture

1. Primary cultures of rainbow trout brain astroglial cells, prelabelled with [1-¹⁴C] polyunsaturated fatty acids (PUFA), were treated with various agents and the effects on cell morphology and n-3 PUFA metabolism were investigated.2. The effects of dibutyryl cAMP on trout astroglial cell cultures were similar to those of dibutyryl cAMP on primary cultures of rat brain astroglia, inducing process-bearing morphology.3. Hydrocortisone had the opposite effect to dibutyryl cAMP on the morphology of the trout astroglial cells, reducing the degree of process-bearing morphology.4. Dibutyryl cAMP increased the percentage of [¹⁴C]eicosapentaenoic acid (EPA, 20:5n-3) elongated to 22:5, whereas hydrocortisone increased the percentage of [¹⁴C]linolenic acid (LNA, 18:3n-3) desaturated and elongated to 20:5.5. Peroxisome effectors also affected trout astroglial cell morphology with the peroxisomal proliferator, clofibrate, reducing the degree of process formation, whereas the peroxisomal inhibitor, 3-aminotriazole, increased the degree of process formation.6. However, the peroxisomal effectors had similar effects on n-3 PUFA metabolism, reducing the percentages of [¹⁴C]LNA converted to 20:5 and 22:5, whereas both increased the percentages of [¹⁴C]EPA converted to 22:5 and 22:6.7. We concluded that changes in the morphology of trout astroglial cells in vitro are not directly related to changes in n-3 PUFA metabolism.     

Metal cluster topology. 4. Rhodium carbonyl clusters having fused polyhedra

Previously discussed topological models of metal cluster bonding are now extended to the treatment of anionic rhodium carbonyl clusters having structures consisting of fused polyhedra. Examples of such rhodium carbonyl clusters built from fused octahedra include the ‘biphenyl analogue’ [Rh₁₂(CO)₃₀]⁻², the ‘face-sharing naphthalene analogue’ [Rh₉- (CO)₁₉]³⁻, and the ‘perinaphthene analogue’, [Rh₁₁- (CO)₂₃]³⁻. More complicated anionic rhodium carbonyl clusters treated in this paper include the [Rh₁₃(CO)₂₄H_5−q]^q− anions (q = 2, 3, 4) having an Rh₁₃ centered cuboctahedron, the [Rh₁₄(CO)₂₅- H_4−q]^q− (q = 3,4) and [Rh₁₄(CO)₂₆]²⁻ anions based on a centered pentacapped cube, the [Rh₁₅- (CO)₃₀]³⁻ anion having an Rh₁₅ centered 14-vertex deltahedron, the [Rh₁₅(CO)₂₇]³⁻ anion having a tricapped centered 11-vertex polyhedron, the [Rh₁₇- (CO)₃₀]³⁻ anion having a tetracapped centered cuboctahedron, and the [Rh₂₂(CO)₃₇]⁴⁻ anion having a hexacapped centered cuboctahedron fused to an octahedron so that the octahedron and the cuboctahedron share a triangular face. Analyses of the bonding topologies in [Rh₉(CO)₁₉]³⁻, [Rh₁₇- (CO)₃₀]³⁻, and [Rh₂₂(CO)₃₇]⁴⁻ indicate that a polyhedral network containing several fused globally delocalized polyhedral chambers will not necessarily have a multicenter core bond in the center of each such polyhedral chamber. This observation is of potential importance in extending topological models of metal cluster bonding to bulk metals.     

Metal cluster topology. 1. Osmium carbonyl clusters

Important theoretical approaches to metal cluster bonding including the Wade-Mingos skeletal electron pair method, the Teo topological electron count, the King-Rouvray graph theory derived method, and Lauher's extended Hückel calculations are shown to agree in their apparent skeletal electron counts for the most prevalent metal cluster polyhedra including the tetrahedron, the trigonal bipyramid (both ordinary and elongated), square pyramid, octahedron, bicapped tetrahedron, pentagonal bipyramid, and capped octahedron. The graph theory derived method is used to treat osmium carbonyl clusters containing from five to eleven osmium atoms. In this connection most osmium carbonyl clusters can be classified into the following types: (1) Clusters exhibiting edge- localized bonding containing multiple tetrahedral chambers (e.g., Os₅(CO)₁₆, Os₆(CO)₁₈, H₂Os₇(CO)₂₀ and HOs₈(CO)₂₂⁻); (2) Capped octahedral clusters derived from osmium carbonyl fragments of the type Os_6+p(CO)_19+2p (p = 0, 1, 2, and 4) (e.g., Os₆- (CO)₁₈²⁻, Os₇(CO)₂₁, Os₈(CO)₂₂²⁻, and H₄Os₁₀- (CO)₂₄²⁻). Other more unusual osmium carbonyl clusters such as the planar Os₆(CO)₁₇ [P(OCH₃)₃]₄, the Os₉ cluster [Os₉(CO)₂₁C₃H₂R]⁻, and the Os₁₁ cluster Os₁₁C(CO)₂₇²⁻ can also be treated satisfactorily by these methods. The importance of the number of ligands around isoelectronic Os_n systems in determining the cluster polyhedron is illustrated by the different cluster polyhedra found for each member of the following isoelectronic pairs: HOs₆- (CO)₁₈⁻/H₂Os₆(CO)₁₈. Os₇(CO)₂₁/H₂Os₇(CO)₂₀, Os₈(CO)₂₂²⁻/HOs₈(CO)₂₂⁻. The tendency for osmium carbonyl clusters frequently to form polyhedra exhibiting edge-localized rather than globally delocalized bonding relates to the facility for osmium carbonyl vertices to contribute more than three internal orbitals to the cluster bonding. In this way Wade's well-known analogy between boron hydride clusters and metal clusters, which assumes exactly three internal orbitals for each vertex atom, is frequently no longer followed in the case of osmium carbonyl clusters.     

Thermodynamics and coordination characteristics of the hydronium-uranium(VI)-dicyclohexano-24-crown-8 extraction complex

The extraction equilibrium of the hydronium-uranium(VI)-dicyclohexano-24-crown-8 complex was carried out in the crown ether1,2-dichloroethaneHCl aqueous solution system at different temperatures. The extraction complex has the overall composition (L)₂·(H₃O⁺·χH₂O)₂·UO₂Cl₄²⁻ (L = dicyclohexano-24-crown-8). The values of the extraction equilibrium constants (K_ex) increase steadily with a decrease in temperature: 13.5 (298 K), 7.96 (301 K), 4.20 (303 K) and 2.07 (305 K). A plot of log K_ex against 1/T shows a straight line. The value of the enthalpy change, ΔH°, was calculated from the slope and equals −212 kJ mol⁻¹. The value of the entropy change, ΔS°, was calculated from ΔH° and K_ex and equals −690 J K⁻¹ mol⁻¹, whereas ΔG° = −6.45 kJ mol⁻¹. Comparing these thermodynamic parameters with those of the dicyclohexano-18-crown-6 isomer A [1] (ΔS° = −314 J K⁻¹ mol⁻¹, ΔH° = −101 kJ mol⁻¹ and ΔG° = −8.37 kJ mol⁻¹), it can be seen that ΔH° and ΔS° are more negative for the former than for the latter, and both are enthalpy-stabilized complexes. The molecular structure of the complex has the feature that there are two H₅O₂⁺ ions in it, in contrast to the H₃O⁺ ions in the dicyclohexano-18-crown-6 isomer A complex [1]. Each of the H₅O₂⁺ ions is held in the crown ether cavity by four hydrogen bonds. The H₅O₂⁺ ion has a central bond. The uranium atom forms UO₂Cl₄²⁻ as a counterion away from the crown ether. The formation of this complex is in good agreement with more negative entropy change and less negative free energy change, as mentioned above.     

An investigation of acid-soluble nuclear proteins of human leucocytes in relation to fraction RP2-L, a component of neoplastic cells

1. The claim that tumour cells contain a specific nuclear protein was investigated. The presence of this component was confirmed in Walker tumour cells by the chromatography on CM-cellulose of nuclear proteins labelled with [¹⁴C]lysine. This protein was studied further in a number of human leucocyte cells. 2. The labelling of leucocyte nuclear proteins with [¹⁴C]lysine was attempted during incubation and culture in vitro. Incorporation of the label into acid-soluble nuclear proteins was highest in normal lymphocytes cultured with phytohaemagglutinin, followed by chronic-myeloid-leukaemic leucocytes and mixed samples of normal leucocytes incubated in plasma. Little incorporation was seen in similar extracts of chronic-lymphatic or normal leucocytes. 3. Lymphocytes were the only cells that gave nuclear extracts with amino acid analysis similar to that of unfractionated histones. 4. Little of the [¹⁴C]lysine in nuclear extracts of incubated leucocytes proved to be of chromosomal origin. No evidence was found of an RP2-L component in the highly labelled nuclear extracts of phytohaemagglutinin-treated lymphocytes until after 6 days of culture with [¹⁴C]lysine. This component was soluble in saline. 5. Evidence is presented that fraction RP2-L is a non-histone protein constituent of cell nuclei whose labelling with [¹⁴C]lysine may be dependent on the metabolic state of the cell. Thus this component is not specific to the neoplastic state.     

Synthesis of carbon-11-labeled CK1 inhibitors as new potential PET radiotracers for imaging of Alzheimer’s disease

The reference standards methyl 3-((2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)carbamoyl)benzoate (5a) and N-(2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)-3-methoxybenzamide (5c), and their corresponding desmethylated precursors 3-((2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)carbamoyl)benzoic acid (6a) and N-(2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)-3-hydroxybenzamide (6b), were synthesized from 5-amino-2,2-difluoro-1,3-benzodioxole and 3-substituted benzoic acids in 5 and 6 steps with 33% and 11%, 30% and 7% overall chemical yield, respectively. Carbon-11-labeled casein kinase 1 (CK1) inhibitors, [¹¹C]methyl 3-((2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)carbamoyl)benzoate ([¹¹C]5a) and N-(2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)-3-[¹¹C]methoxybenzamide ([¹¹C]5c), were prepared from their O-desmethylated precursor 6a or 6b with [¹¹C]CH₃OTf through O-[¹¹C]methylation and isolated by HPLC combined with SPE in 40–45% radiochemical yield, based on [¹¹C]CO₂ and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the molar activity (MA) at EOB was 370–740?GBq/μmol with a total synthesis time of ～40-min from EOB.     

Synthesis,Characterization, and Biological Study of 3-Trifluoromethylpyrazole Tethered Chalcone-Pyrrole and Pyrazoline-Pyrrole Derivatives

The present study illustrates the design and synthesis of new series of 3-trifluoromethylpyrazole tethered chalcone-pyrrole and pyrazoline-pyrrole derivatives. All compounds were further screened for in vitro cytostatic activities on full NCI 60 cancer cell lines at National Cancer Institute, USA. Compounds (2E)-3-(1H-pyrrol-2-yl)-1-{4-[3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl}prop-2-en-1-one ( 5a ) and (2E)-1-{3-methyl-4-[3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl}-3-(1H-pyrrol-2-yl)prop-2-en-1-one ( 5c ) displayed significant antiproliferative activity (Growth Percentage: −77.10 and −92.13, respectively at 10 μM concentration) against the UO-31 cell lines from renal cancer and were further selected for assay at 10-fold dilutions of five different concentrations (10⁻⁴ to 10⁻⁸ M). Both compounds 5a and 5c exhibited promising antiproliferative activity (GI₅₀: 1.36 to 0.27 μM) against leukemia cancer cell lines HL-60 and RPMI-8226, colon cancer cell lines KM-12; breast cancer cell lines BT-549. Moreover, both compounds 5a and 5c were found to be non-cytotoxic (LC₅₀>100) against HL-60, RPMI-8226, and KM-12 cell lines. Remarkably, GI₅₀ values of compounds 5a and 5c were identified as more promising than sunitinib against most cancer cell lines. In silico study of compounds 5a and 5c exemplified the desired ADME properties for drug-likeness as well as tighter interactions with VEGFR-2. Hence, compounds 5a and 5c would be good cytotoxic agents after further clinical study.