A chemical inhibitor reveals the role of Raf kinase inhibitor protein in cell migration

Raf kinase inhibitor protein (RKIP) is a modulator of cell signaling that functions as an endogenous inhibitor of multiple kinases. We demonstrate here a positive role for RKIP in the regulation of cell locomotion. We discovered that RKIP is the relevant cellular target of locostatin, a cell migration inhibitor. Locostatin abrogates RKIP's ability to bind and inhibit Raf-1 kinase, and it acts by disrupting a protein-protein interaction, an uncommon mode of action for a small molecule. Small interfering RNA-mediated silencing of RKIP expression also reduces cell migration rate. Overexpression of RKIP converts epithelial cells to a highly migratory fibroblast-like phenotype, with dramatic reduction in the sensitivity of cells to locostatin. RKIP is therefore the compound's valid target and a key regulator of cell motility.     

The convergence of the Rayleigh-Ritz Method in quantum chemistry

Two sufficient criteria for the convergence of the Rayleigh-Ritz Method (RRM) with respect to the eigenvalues (E-convergence) of non-relativistic electronic Hamiltonians of molecules are discussed and compared. Moreover, a necessary and sufficient criterion is given. By example (Sect. 9) it is shown that the L ²-completeness of the basis is not sufficient to guarantee E-convergence. The convergence of the wave functions in different norms (-convergence) is also investigated. In particular, sufficient conditions for the one-particle basis functions (orbitals) are given, such that a CI calculation in this basis is both E- and -convergent.     

Réactions de germylènes avec divers oxirannes et le thiiranne. Mise en évidence de germanones et germathiones intermédiaires. Communication préliminaire

Complexed dialkylgermylenes R₂GeNR₃ or R₂GePy react with oxiranes or thiirane and lead to dialkylgermanone and germathione via germaoxetanes or germathiacyclobutane. The formation of germadioxolanes or germadithiolane finally observed arises from condensation of dialkylgermanone (or germathione) on oxiranes (or thiirane).     

MP2 study of substituent effects of 2-substituted alkyl ethyl methylcarbamates in homogeneous, unimolecular gas phase elimination reaction

Møller-Plesset MP2/6-31G method was used to examine the gas-phase elimination of 2-substituted alkyl ethyl N,N-dimethylcarbamates. The results of these calculations support a concerted non-synchronous six-membered cyclic transition state mechanism for carbamates containing a C_β–H bond at the alkyl side of the ester. These substrates produce the N,N-dimethylcarbamic acid and the corresponding olefin. The unstable intermediate, N,N-dimethylcarbamic acid, rapidly decomposes through a four-membered cyclic transition state to dimethylamine and CO₂ gas. Correlation of the logarithm of theoretical rate coefficients against original Taft's σ* values gave an approximate straight line (ρ*=−1.39, r=0.9558 at 360 °C). In addition to this fact, when log k_rel is plotted against the theoretical log k_rel for 2-substituted ethyl N,N-dimethylcarbamates a reasonable straight line (r=0.9919 at 360 °C) is obtained, suggesting similar mechanism.     

Chemical ionization desorption mass spectrometry of some quaternary ammonium salts

The ammonia chemical ionization desorption spectra of N,N-dimethyl quaternary ammonium iodides in addition to high protonated molecular ion [M + H]⁺ intensity, show signals for an ion radical composed of N-methyl abstracted salt cation and ammonia [C + NH₃? CH₃]^+˙. These ions corresponding to the cation +2 show increased importance in the chemical ionization mode, using the same reagent gas. The technique of chemical ionization desorption appears suitable for the analysis of salts, and thus for the determination of the molecular weight of both anion and cation.     

Conformationally Controlled Odor Perception in ‘Steroid-type’ Scent Molecules

A series of compounds possessing a ‘Steroid-type’ scent and related to 4-(4′-t-butylcyclohexyl)-4-methyl-2-pentanones ( 1 and 2 ) has been synthesized. The odor of these compounds has been found to be dependent on their conformation; only when the molecule can assume a steroid-like shape there is an interaction with the odor chemoreceptor.     

Glycosylidene Carbenes. Part 15. Synthesis of disaccharides from allopyranose-derived vicinal 1,2-diols. Evidence for the protonation by a H-bonded hydroxy group in the σ-plane of the intermediate carbene,followed by attack on the oxycarbenium ion in the π-plane

The α-D -allo-diol 9 possesses an intramolecular H-bond (HO? C(3) to O? C(1)) in solution and in the solid state (Fig. 2). In solution, it exists as a mixture of the tautomers 9a and 9b (Fig. 3), which possess a bifurcated H-bond, connecting HO? C(2) with both O? C(1) and O? C(3). In addition, 9a possesses the same intramolecular H-bond as in the solid state, while 9b is characterized by an intramolecular H-bond between HO? C(3) and O? C(4). In solution, the β-D -anomer 12 is also a mixture of tautomers, 12a and presumably a dimer. The H-bonding in 9 and 12 is evidenced by their IR and ¹H-NMR spectra and by a comparison with those of 3–8, 10 , and 11 . The expected regioselectivity of glycosidation of 9 and 12 by the diazirine 1 or the trichloroacetimidate 2 is discussed on the basis of the relative degree of acidity/nucleophilicity of individual OH groups, as governed by H-bonding. Additional factors determining the regioselectivity of glycosidation by 1 are the direction of carbene approach/proton transfer by H-bonded OH groups, and the stereoelectronic control of both the proton transfer to the alkoxy-alkyl carbene (in the σ-plane) and the combination of the thereby formed ions (π-plane of the oxycarbenium ion). Glycosidation of 9 by the diazirine 1 or the trichloroacetimidate 2 proceeded in good yields (75–94%) and with high regioselectivity. Glycosidation of 9 and 12 by 1 or 2 gave mixtures of the disaccharides 14–17 and 18–21 , respectively (Scheme 2). As expected, glycosidation of 12 by 1 or by 2 gave a nearly 1:1 mixture of regioisomers and a slight preference for the β-D -anomers (Table 4). Glycosidation of the α-D -anomer 9 gave mostly the 1,3-linked disaccharides 16 and 17 (α-D β-D ) along with the 1,2-linked disaccharides 14 and 15 (α-D < β-D , 1,2-/1,3-linked glycosides ca. 1:4), except in THF and at low temperature, where the β-D -configurated 1,2-linked disaccharide 15 is predominantly formed. Similarly, glycosidation of 9 with 2 yielded mainly the 1,3-linked disaccharides (1,2-/1,3-linked products ca. 1:3 and α-D /β-D ca. 1:4). Yields and selectivity depend upon the solvent and the temperature. The regioselectivity and the unexpected stereoselectivity of the glycosidation of 9 by 1 evidences the combined effect of the above mentioned factors, which also explain the lack of regio-complementarity in the glycosidation of 9 by 1 and by 2 (Scheme 3). THF solvates the intermediate oxycarbenium ion, as evidenced by the strong influence of this solvent on the regio- and stereoselectivity, particularly at low temperatures, where kinetic control leads to a stereoelectronically preferred axial attack of THF on the oxycarbenium ion.     

Xanthones and other constituents of Allanblackia monticola (Guttiferae)

A xanthone derivative, 3,6,7-trihydroxy-1-methoxyxanthone has been isolated from the stem bark of Allanblackia monticola together with other known compounds, 2,6-dihydroxy-1-methoxyxanthone, allanxanthone A, epicathechin and oleanolic acid acetate. The structure of the new compound was elucidated by spectroscopic methods.     

Confirmation of the Structures of Lutein and Zeaxanthin

A series of new esters of lutein ( 1a ) have been prepared with the aim of confirming the structure of lutein via an X‐ray crystal‐structure analysis. Although well crystallized, only one of the derivatives, the (?)‐(1R)‐menthyl carbonate ( 1i ) proved to be useful for a complete structure analysis. The same derivative of zeaxanthin ( 2a ) also allowed its crystal structure to be determined. Both analyses represent the first successful X‐ray crystal structure analyses of the most important xanthophylls. At the same time, they confirm both the constitution and absolute configuration of 1a and 2a that had been deduced earlier by classical methods.     

Kalorimetrische untersuchung flüssiger indium—kadmium-legierungen unter dem aspekt von assoziationsgleichgewichten

Enthalpies of mixing of liquid In—Cd alloys were determined over the entire concentration range using a sensitive calorimeter. Deviations of this system from regular behavior can be explained by the existence of associates in the alloy melts. Furthermore the concentration dependence of the enthalpies of mixing were explained, with the help of a previously derived model, by the existence of associates of the composition InCd₃. Moreover the possibility was discussed that associates of a different stoichiometric composition occur in liquid In—Cd alloys, by which the discrepancies of earlier experimental results with the isopiestic method can be clarified.