Bis(tetraphenylphosphonium) (hexasulfido‐2κ2S1,S6)di‐μ‐sulfido‐disulfido‐1κ2S‐tungsten(VI)zinc(II) acetone solvate

The title complex, (C₂₄H₂₀P)₂[WZnS₄(S₆)]·C₃H₆O or (Ph₄P)₂[WS₂(μ‐S)₂{Zn(S₆)}]·Me₂CO, was unexpectedly obtained on attempted recrystallization of a mixed tungten–zinc complex of a tris(pyrazolato)borate ligand. The two metal centres of the anion have distorted tetrahedral coordination and the two tetrahedra share one S...S edge; tungsten is additionally coordinated by two terminal sulfide ligands and zinc by a chelating S₆²⁻ ligand, which has one central S—S bond significantly longer than the other four, a pattern found to be consistent for this ligand. This is the first reported example of a tetrahedral zinc centre bridging an edge of a single tetrathiotungstate(VI) or tetrathiomolybdate(VI) anion, although there are many previous examples with other metals.     

Total synthesis of chlorofusin, its seven chromophore diastereomers, and key partial structures

Chlorofusin is a recently isolated, naturally occurring inhibitor of p53-MDM2 complex formation whose structure is composed of a densely functionalized azaphilone-derived chromophore linked through the terminal amine of ornithine to a nine residue cyclic peptide. Herein we report the full details of the total synthesis of chlorofusin, resulting in the assignment of the absolute stereochemistry and reassignment of the relative stereochemistry of the complex chromophore. Condensation of each enantiomer of an azaphilone chromophore precursor with the N(delta)-amine of a protected ornithine-threonine dipeptide, followed by a one-step oxidation/spirocyclization of the most reactive olefin provided all eight diastereomers of the fully elaborated chromophore-dipeptide conjugate. Comparison of the spectroscopic properties for these eight compounds and those of simpler models with that reported for the natural product allowed the full assignment of the (4R,8S,9R)-stereochemistry of the chlorofusin chromophore. The natural, but stereochemically reassigned, diastereomer of the dipeptide conjugate was incorporated in a convergent total synthesis of chlorofusin confirming the stereochemical reassignment and establishing its absolute stereochemistry. Similarly and enlisting the late stage convergent point in the total synthesis, the remaining seven diastereomers of the chromophore-dipeptide conjugates were individually incorporated into the nine-residue cyclic peptide of chlorofusin (4 steps each) providing all seven remaining possible chromophore diastereomers of the natural product.     

Yatakemycin: total synthesis, DNA alkylation, and biological properties

DNA-binding small molecules are an important source of anticancer therapeutics that display a diverse array of mechanisms of action. Synthetic studies on the new DNA-alkylating natural product yatakemycin, detailed in this Highlight, have served to reassign its structure, assign the absolute stereochemistry, and provide access to yatakemycin and a series of structural analogues for biological evaluation. Studies on the DNA alkylation properties of (+)-and ent-(-)-yatakemycin and related analogues have demonstrated the enhanced DNA alkylation properties of this class of agents and provided insight into their interaction with DNA.     

Effects of glucose,glutamine, and malate on the metabolism of spodoptera frugiperda clone 9 (sf9) cells

Optimal design and operation of bioreactors for insect cell culture is facilitated by functional relations providing quantitative information on cellular metabolite consumption kinetics, as well as on the specific cell growth rates (μ_G). Initial specific consumption rates of glucose, malate, and oxygen, and associated changes in μ_G, were measured forSpodoptera frugiperda clone 9 (Sf9) cells grown in batch suspension culture in medium containing 7–35 mM glucose, 0–16 mM malate, and 4–16 mM glutamine. The initial specific glucose consumption rate (q _G ) could be described by a modified Michaelis-Menten equation treating malate as a “competitive” inhibitorK ₁ = 6.5 mM) and glutamine as a “noncompetitive” inhibitorK _I = 14 mM) ofq _G , with aK _m of 7.1 mM for glucose. All three carbon sources were found to increase μ_G in a saturable manner, and a modified Monod equation was employed to describe this relationship (μ_Gmax = 0.047 h^-1). The initial specific oxygen consumption rate (q_O2) in Sf9 cells could be related to μ_G by the maintenance energy model, and it was calculated that, under typical culture conditions, about 15–20% of the cellular energy demand comes from functions not related to growth. Fitted parameters in mathematical expression for μg: K₄, Monod constant for glucose (mM); K₅, modified Monod constant for malate (mM); K₆, Monod constant for glutamine (mM); m_o2, specific consumption rate of oxygen by the cells under zero-growth conditions (nmol/cell/h); q_F, initial specific fumarate production rate (nmol/cell/ h);q _G , initial specific glucose consumption rate (nmol/cell/h); q_Gmax, maximum initial specific glucose consumption rate (nmol/cell/h);q _M , initial specific malate consumption rate (nmol/cell/h); q_o2, initial specific oxygen consumption rate (nmol/cell/h); Y_o2, cell yield on oxygen (cells/nmol); μ, initial specific cell growth rate (h^-1); μ_g, initial specific cell growth rate (h^-1); μG_max, maximum initial specific cell growth rate (h^-1).     

A shell model for tyre belt vibrations

We present a new formulation for the prediction of tyre belt vibrations in the frequency range 0-500 Hz. Our representation includes the effects of belt width, curvature and anisotropy, and also explicitly models the tyre sidewalls. Many of the associated numerical parameters are fixed by physical considerations; the remainder require empirical input. A systematic and general approach to this problem is developed, and illustrated for the specific example of a Goodyear Wrangler tyre. The resulting predictions for the radial response to radial forcing show good correspondence with experiment up to 300 Hz, and satisfactory agreement up to 1 kHz.     

Quotients ofC[0, 1] with separable dual

A necessary and sufficient condition for an operator fromC(K),K compact metric, into a Banach spaceX to be an isomorphism on a subspace ofC(K) isometric toC ₀(ω ^ω ) is given. This is part of the author’s Ph.D. dissertation being prepared at the Ohio State University under the supervision of Professor W. B. Johnson. This research was supported in part by NSF grant MPS 72-04634-A03 and a University Fellowship of the Ohio State University.     

Muon/muonium surface interactions

The interactions of muonium (μ ⁺ e ⁻, Mu) with the surfaces of fine silica powders have been extensively studied using zero, longitudinal and transverse field μSR techniques. These studies indicate diffusion and trapping behavior of the Mu atoms on the silica surface, which is strongly influenced by the surface hydroxyl (OH) concentration. Specifically, the presence of the surface OH groups is observed to inhibit the surface mobility of the Mu atoms at low temperatures. Information provided by zero and longitudinal field data suggest a random anisotropic distortion of the Mu hyperfine interaction (RAHD) as the principal relaxation mechanism. A recently developed RAHD spin relaxation theory is used to interpret these data. Additional investigations, using platinum loaded silica, have yielded the first observed surface reaction of Mu. Studies of the interactions of positive muons with surfaces have been also extended to single crystals, where low energy (<10 eV)μ ⁺ andMu ⁻ ions are observed to be reemitted from some materials (e.g., the <100> surface of lithium fluoride). Future applications of these emission phenomena toward the development of a slow^847-3 (or Mu⁻) beam are considered.     

Muonium in bulk fused quartz: Test case for RAHD relaxation theory

Muonium (μ ⁺ e ⁻) in bulk fused quartz is a unique system in that theμ ⁺ spin polarization (in the muonium state) relaxes almost entirely via random anisotropic hyperfine distortions (RAHD). As such, this system provides an excellent test case for a new RAHD spin relaxation theory. This theory is quantitatively compared to static zero field data and the functional characteristics in both the high field and dynamic limits are considered as well.     

Evaluation of chlorofusin, its seven chromophore diastereomers, and key analogues

Chlorofusin, its seven chromophore diastereomers, and key analogues were comparatively examined for inhibition of MDM2-p53 binding revealing that the chromophore, but not simple replacements, contributes significantly to the natural products properties, and that this contribution is independent of its relative and absolute stereochemistry.