Reactions of 14-hydroxy-14-azadispiro[5.1.5.2]pentadec-9-ene-7,15-dione and related compounds. II

3 When 11-diethyl- and 3, 11-di-n-propyl-14-hydroxy-14-azadispiro[5.1. 5.2]pentadec-9-ene-7, 15-dione (E-IV and n-Pr-IV) are heated with polyphosphoric acid at 55–65°, the 14-hydroxyl group cyclizes at the 11-carbon to form E-VI and n-Pr-VI, the structures of which have been established. Compounds P-IV, i-Pr-IV and t-B-IV do not cyclize under these conditions. The Beckmann rearrangement of 12-hydroxy-12-azadispiro[4.1.4.2]tridec-8-ene-6, 13-dione-6-oxime (P-I) with polyphosphoric acid at 40–50° formed only the normal product, P-II, which could not be cyclized. Compound P-IV was the only ketone of this series which would add hydrogen cyanide to form a cyanohydrin.     

Hydride donor abilities and bond dissociation free energies of transition metal formyl complexes

The hydride complex [Pt(dmpe)2H]+ (dmpe = 1,2-bis(dimethylphosphino)ethane) reversibly transfers H- to the rhenium carbonyl complex [CpRe(PMe3)(NO)(CO)]+, giving the formyl CpRe(PMe3)(NO)(CHO). From the equilibrium constant for the hydride transfer (16.2), the DeltaGdegrees for the reaction was determined (-1.6 kcal/mol), as was the hydride-donating ability of the formyl (44.1 kcal/mol). The hydride-donating ability, DeltaGdegrees(H-), is defined as the energy required to release the hydride ion into solution by the formyl complex [i.e. M(CHO) right arrow M(CO)+ + H-]. Subsequently, the hydride-donating ability of a series of formyl complexes was determined, ranging from 44 to 55 kcal/mol. With use of this information, two rhenium carbonyl complexes, [CpRe(NO)(CO)2]+ and [Cp*Re(NO)(CO)2]+, were hydrogenated to formyls, employing [Pt(dmpp)2]2+ and Proton-Sponge. Finally, the E(1/2)(I/0) values for five rhenium carbonyl complexes were measured by cyclic voltammetry. Combined with the known DeltaGdegrees(H-) values for the complexes, the hydrogen atom donating abilities could be determined. These values were all found to be approximately 50 kcal/mol.     

Dyeing uric acid crystals with methylene blue

The growth of anhydrous uric acid (UA) and uric acid dihydrate (UAD) crystals from supersaturated aqueous solutions containing methylene blue, a cationic organic dye, has been investigated. Low concentrations of dye molecules were found to be included in both types of crystal matrixes during the growth process. Incorporation of dye into UA crystals occurs with high specificity, affecting primarily [001] and [201] growth sectors, while UAD crystals grown from solutions of similar dye concentration show inclusion but little specificity. The orientation of the UA-trapped species was determined from polarization data obtained from visible light microspectrometry. To achieve charge neutrality, a second anionic species must also be included with the methylene blue into UA and UAD crystal matrices. Under high pH conditions, crystallization of 1:1 stoichiometric mixtures of methylene blue and urate yields methylene blue hexahydrate (MBU.6(H2O). The crystal structure of MBU.6(H2O) reveals continuous pi-pi stacks of planes of dye cations and urate anions mediated by water molecules. This structure provides an optimal geometry for methylene blue-urate pairs and additional support for the incorporation of these dimers in uric acid single-crystal matrices. The strikingly different inclusion patterns in UA and UAD demonstrate that subtle changes in the crystal surfaces and/or growth dynamics can greatly affect recognition events.     

Determination of a novel antifibrotic small molecule GDC‐3280 in human plasma and urine by liquid chromatography tandem mass spectrometry to support its first‐in‐human clinical trial

A specific and robust LC–MS/MS method was developed and validated for the quantitative determination of GDC‐3280 in human plasma and urine. The nonspecific binding associated with urine samples was overcome by the addition of CHAPS. The sample volume was 25 μL for either matrix, and supported liquid extraction was employed for analyte extraction. d6‐GDC‐3280 was used as the internal standard. Linear standard curves (R² > 0.9956) were established from 5.00 to 5000 ng/mL in both matrices with quantitation extended to 50,000 ng/mL through dilution. In plasma matrix, the precision (RSD) ranged from 1.5 to 9.9% (intra‐run) and from 2.4 to 7.2% (inter‐run); the accuracy (RE) ranged from 96.1 to 107% (intra‐run) and from 96.7 to 104% (inter‐run). Similarly, in urine the precision was 1.5–6.2% (intra‐run) and 1.9–6.1% (inter‐run); the accuracy was 83.1–99.3% (intra‐run) and 87.1–98.3% (inter‐run). Good recovery (>94%) and negligible matrix effect were achieved in both matrices. Long‐term matrix stability was established for at least 703 days in plasma and 477 days in urine. Bench‐top stability of 25 h and five freeze–thaw cycles were also confirmed in both matrices. The method was successfully implemented in GDC‐3280's first‐in‐human trial for assessing its pharmacokinetic profiles.     

Tri­carbonyl­[1,1′,1′′-ethyl­idyne­tris­(pyrazole-κN2)]­rhenium(I) bromide and tri­carbonyl­[methyl­idyne­tris­(pyrazole-κN2)]­rhenium(I) iodide ethanol hemisolvate

The two title compounds, [Re(C₁₀H₁₀N₆)(CO)₃]Br and [Re(C₁₁H₁₂N₆)(CO)₃]I·0.5C₂H₆O, have slightly distorted octahedral geometries about the rhenium centers. The distortions result from the constraints of the η³-coordinated tris­(pyrazol-1-yl)­methane ligands in each case which reduce the N—Re—N bond angles well below the preferred value of 90° for facially disposed ligands at a six-coordinate metal center.     

Acoustic features of male baboon loud calls: influences of context, age, and individuality

The acoustic structure of loud calls ("wahoos") recorded from free-ranging male baboons (Papio cynocephalus ursinus) in the Moremi Game Reserve, Botswana, was examined for differences between and within contexts, using calls given in response to predators (alarm wahoos), during male contests (contest wahoos), and when a male had become separated from the group (contact wahoos). Calls were recorded from adolescent, subadult, and adult males. In addition, male alarm calls were compared with those recorded from females. Despite their superficial acoustic similarity, the analysis revealed a number of significant differences between alarm, contest, and contact wahoos. Contest wahoos are given at a much higher rate, exhibit lower frequency characteristics, have a longer "hoo" duration, and a relatively louder "hoo" portion than alarm wahoos. Contact wahoos are acoustically similar to contest wahoos, but are given at a much lower rate. Both alarm and contest wahoos also exhibit significant differences among individuals. Some of the acoustic features that vary in relation to age and sex presumably reflect differences in body size, whereas others are possibly related to male stamina and endurance. The finding that calls serving markedly different functions constitute variants of the same general call type suggests that the vocal production in nonhuman primates is evolutionarily constrained.     

Magnetic interactions of iron nanoparticles in arrays and dilute dispersions

The magnetic properties of monodisperse Fe nanoparticles with over 4 orders of magnitude difference in concentration are studied by a combination of ordinary and remanent hysteresis loops, zero field cooled magnetization as a function of temperature, and magnetic relaxation rates. We compare the behavior of dilute dispersions with different concentrations, dispersions, and arrays made from the same particles, and nanoparticle arrays with different particle sizes and separations. The results are related to theoretical predictions and are used to create a unified picture of magnetostatic interactions within the assemblies.     

Simulations of calcite crystallization on self-assembled monolayers

This paper presents simulations of calcium carbonate ordering in contact with self-assembled monolayers. The calculations use potential-based molecular dynamics to model the crystallization of calcium carbonate to calcite expressing both the (00.1) and (01.2) surfaces. The effect of monolayer properties: ionization; epitaxial matching; charge density; and headgroup orientation on the crystallization process are examined in detail. The results demonstrate that highly charged surfaces are vital to stimulate ordering and crystallization. Template directed crystallization requires charge epitaxy between both the crystal surface and the monolayer. The orientation of the headgroup appears to make no contribution to the selection of the crystal surface.