Multifunctional behavior by a Bis-(phosphinimino)methanide ligand: eta 2- vs eta 3-coordination vs Bronsted basicity

The reaction of [(Cymene)RuCl2]2 with the chelate LiHC(PPh2NPh)2 occurs to remove both chloride ligands, to furnish a cationic Ru(II) complex with the monoanionic ligand bound eta3, through two N and an sp3 carbon. This cation is also produced from the conjugate acid of the ligand H2C(PPh2NPh)2 because this molecule can serve as a Br?nsted base, to deprotonate the acidic carbon of another molecule of H2C(PPh2NPh)2. DFT calculations show an energy surface where (Cymene)RuHC(PPh2NPh)2L is more stable with a Ru-CH(PPh2NPh)2 bond and with L = Cl- or MeCN not coordinated to Ru, than to an eta2-HC(PPh2NPh)2 structure with coordinated L; this is tested experimentally. The greater tendency for this ligand to be coordinated eta3 vs analogous diketiminates is discussed. The nucleophilicity of Cgamma in structure 1, vs that of donors L = Cl- or MeCN, is evaluated to understand the preference of the bis(phosphinimino)methanide to be bidentate or tridentate.     

Definitive Proof for the Operation of Isotopically Sensitive Branching (‘Metabolic Switching’) in FeI-Mediated C?H Bond Activation in the Gas Phase Short Communication

Rigorous regio- and stereospecific labeling experiments are performed to demonstrate the operation of the previously suggested operation of ‘isotopically sensitive branching’ in Fe^I-mediated C? H bond activation. For the hexane-1,6-diol/Fe⁺-complex, it is shown that dehydrogenation involves specifically the central C(3)/C(4) position, and the study of the stereospecifically labeled D ,L - and meso-[3,4-D₂]-isotompomers 1e and 1f demonstrates that dehydrogenation proceedes via two competing pathways (i.e. ‘anti’- vs. ‘syn’-route). The contribution of these routes to the product formation is – due to a kinetic isotope effect – controlled by the relative configuration at the labeled positions C(3)/C(4). For the D ,L -form 1e , we estimate a ratio of 49:1 in favor of the ‘anti’-route; due to an isotope effect, this ratio drops to 4.3:1 for the meso-form 1f .     

Squeezing the [Cu-OH...H2O-Cu]3+ bridge by cryptate encapsulation

Treatment of cryptand L(1) with Cu(II) generates a H3O2(-)-bridged dicopper(II) cryptate, 2, where the guest anion has responded to steric constraint by a significant shortening of the O-O distance to 2.325(9) A; computational optimization at the B3LYP/6-31(d) level suggests that the bridging O-H...O H-bond is bent (approximately 157 degrees) but that the barrier to interchange of the bridging H atom is low (<4 kJ mol(-1)). This cryptate, rather than the [Cu2L(1)muCN]3+ species recently claimed to derive from cleavage of the C-C bond of the solvent, is the product of acetonitrile recrystallization of the initially formed reaction product, 1.     

Estimating entropies from molecular dynamics simulations

While the determination of free-energy differences by MD simulation has become a standard procedure for which many techniques have been developed, total entropies and entropy differences are still hardly ever computed. An overview of techniques to determine entropy differences is given, and the accuracy and convergence behavior of five methods based on thermodynamic integration and perturbation techniques was evaluated using liquid water as a test system. Reasonably accurate entropy differences are obtained through thermodynamic integration in which many copies of a solute are desolvated. When only one solute molecule is involved, only two methods seem to yield useful results, the calculation of solute-solvent entropy through thermodynamic integration, and the calculation of solvation entropy through the temperature derivative of the corresponding free-energy difference. One-step perturbation methods seem unsuitable to obtain entropy estimates.     

Synthesen von Xyluron- und Riburonsäurederivaten

Zusammenfassung Durch acylierende Dehydratisierung von 1,2-Isopropyliden-d-xylo-und-d-ribo-pentodialdo-furanoseoxim bzw. aus Furanuronsäureestern und-amiden werden über eine Reihe von Zwischenstufen verschiedene 3-O-Acyl-pentofuranuronsäurenitrile synthetisiert und deren Reaktionen untersucht.

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Synthesis of xyluronic and riburonic acid derivatives

Various 3-O-acyl-pentofuranurononitrils were synthesized by acylating dehydration of 1,2-isopropylidene-d-xylo- andd-ribo-pentodialdo-furanose oximes, or pentofuranuronic acids via intermediates. Their reactions were investigated.

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Mit 1 Abbildung

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Aus den DissertationenH. W. Oberwalder (1970) undE. Wildschek (1967), Technische Hochschule in Graz.     

Explanation of the real stress-strain-behavior of elastomers

Summary The deviation from the statistical theory of rubberelasticity in the stress-strain-behavior of elastomers, which is described empirically by theRivlin-Mooney equation for the case of simple elongation, is explained by the cooperation of the short range order, which is to assume in amorphous polymers, and the chain length distribution and the occurrence of chain ends in crosslinked systems. This explanation is in qualitative agreement with all experimental results regarding the influence of swelling, preparation of the networks and type of deformation. The quantitative agreement is as good as one can expect from the underlying simple model. In particular the influence of the crosslinking density and the primary molecular weight is considered. In connection with this theory conclusions are drawn to the short range order and a remark is made concerning the problem of the crosslinking density.

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Zusammenfassung Die Abweichung von der statistischen Theorie der Kautschukelastizität im Spannungs-Dehnungs-Verhalten von Elastomeren, die im Falle der uniaxialen Dehnung durch dieRivlin-Mooney-Gleichung beschrieben wird, wird erklärt durch das Zusammenwirken der Nahordnung, die in amorphen Polymeren anzunehmen ist, und der Kettenlängenverteilung sowie das Vorhandensein von freien Kettenenden in vernetzten Systemen. Die gegebene Erklärung stimmt qualitativ mit allen experimentellen Ergebnissen überein bezüglich des Einflusses der Quellung, der Herstellung der Netzwerke und der Art der Deformation. Die quantitative Übereinstimmung ist so gut, wie man es nach dem zugrunde liegenden einfachen Modell erwarten kann. Insbesondere wird der Einfluß der Vernetzungsdichte und des Molekulargewichts vor der Vernetzung betrachtet. Im Zusammenhang mit dieser Theorie werden Folgerungen bezüglich der Nahordnung gezogen und eine Betrachtung zum Problem der Vernetzungsdichte angestellt.

     

Multidrug resistance and cancer: the role of the human ABC transporter ABCG2

A variety of human cancers become resistant or are intrinsically resistant to treatment with conventional chemotherapy, a phenomenon called multidrug resistance. This broad-based resistance results in large part, but not solely, from overexpression of members of the ATP-binding cassette (ABC) superfamily of membrane transporters, including P-glycoprotein, various members of the multidrug resistance associated proteins (MRPs), and ABCG2, also known as MXR1, BCRP, and ABCP. When overexpressed in cell lines, ABCG2 has the ability to confer high levels of resistance to anthracyclines, mitoxantrone, bisantrene, and the camptothecins topotecan and SN-38. This review focuses on the discovery, the biochemistry and the normal physiology of human ABCG2, a novel ABC half transporter expressed abundantly in placenta, as well as in liver, intestine and stem cells. ABCG2 may serve a protective function by preventing toxins from entering cells as well as potentially playing a role in regulating stem cell differentiation. We also discuss the involvement of ABCG2 in multidrug resistance in cancer, especially with regard to acute myeloid leukemia. The mechanism by which substrates are recognized by ABCG2 and how the energy of ATP hydrolysis is transduced into transport remain elusive. A complete understanding of the mechanism and biological function of ABCG2 will be important for understanding its normal physiology as well as potentially for the development of novel chemotherapeutic treatment strategies.     

Synthese und Struktur von [(Ph3PAu)3NPPh3][PF6]2, einem Gold(I)‐phosphoraniminato‐Komplex

Synthesis and Crystal Structure of [(Ph₃PAu)₃NPPh₃][PF₆]₂, a Gold(I) Phosphoraneiminato Complex The photolytic reaction of Ph₃PAuN₃ with Cr(CO)₆ in THF yields the phosphoraneiminato complex [(Ph₃PAu)₃NPPh₃]²⁺ in low yield as well as the cluster cation [(Ph₃PAu)₈]²⁺ as the main product. The phosphoraneiminato complex crystallizes from CH₂Cl₂ with [PF₆]^? ions as [(Ph₃PAu)₃NPPh₃][PF₆]₂·CH₂Cl₂ in the triclinic space group with a = 1200.8(1), b = 1495.6(2), 2053.5(5), α = 86.97(2)°, β = 82.79(1)°, γ = 81.87(2)°, and Z = 2. The phosphoraneiminato ligand bridges through its N atom three Au atoms, which itself are connected to each other by weak aurophilic interactions.     

UVA-INDUCED AUTOCRINE STIMULATION OF FIBROBLAST-DERIVED COLLAGENASE/MMP-1 BY INTERRELATED LOOPS OFINTERLEUKIN–1 andINTERLEUKIN–6

Abstract— Previous work has shown that fibroblast-derived collagenase/matrix-metalloproteinase-1(MMP–1), responsible for the breakdown of dermal interstitial collagen, was dose-dependently induced in vitro and in vivo by UVA irradiation and this induction was at least partly mediated byinterleukin–6(IL–6). We here provide evidence that UVA-inducedIL–1α andIL–1β play a central role in the induction of the synthesis both ofIL–6 and collagenase/MMP–1. In contrast to the late increase ofIL–1α andIL–1β mRNA levels at 6 h postirradiation, bioactivity ofIL–1 is already detectable at 1 h postirradiation. This early peak ofIL–1 bioactivity appears to be responsible for the induction ofIL–6 synthesis and together withIL–6 lead to an increase of the steady-state mRNA level of collagenase/MMP–1 as deduced from studies usingIL–1α andIL–1β antisense oligonucleotides or neutralizing antibodies againstIL–1α andIL–1β Besides the early posttranslationally controlled release of intracellularIL–1, a latter pretranslationally controlled synthesis and release ofIL–1 perpetuates the UV response. From these data we suggest a UV-induced cytokine network consisting ofIL–1α,IL–1β andIL–6, which via interrelated autocrine loops induce collagenase/MMP–1 and thus may contribute to the loss of interstitial collagen in cutaneous photoaging.     

exo/endo-Selectivity in the Reaction of ‘Bare’ FeO+ with Bicyclo[2.2.1]heptane (Norbornane)

‘Bare’ FeO⁺ reacts in the gas phase with norbornane with collision efficiency, and the most prominent cationic products correspond to [FeC₅H₆]⁺ (32%), [FeC₇H₈]⁺ (19%), [FeC₃H₆O]⁺ (19%) and [FeC₆H₆]⁺ (14%), which are structurally characterized by ligand exchange as well as collision-induced dissociation experiments. Circumstantial evidence is provided which indicates that the complexes [FeC₅H₆]⁺, [FeC₇H₈]⁺, and [FeC₆H₆]⁺ originate from an Fe(norbornene)⁺ intermediate which itself is formed by elimination of H₂O from the [FeO(norbornane)]⁺ encounter complex. Although the reactions are preceded and/or accompanied by partial H/D exchange, the isotope distribution in the productions clearly points to a preferential endo-attack of bare FeO⁺, with an endo/exo-ratio of ca. 10.3 and kinetic isotope effects k_H/k_D for the endo-abstraction of 2.4 and of 7.7 for approaching an exo-C? H bond. The preferred endo-approach of bicyclo[2.2.1]heptane by ‘bare’ FeO⁺ is in distinct contrast to the P-450-mediated or the iron(III)porphyrin-catalyzed hydroxylation of this substrate which favor reactions at the exo-face.