Susanne Wagner

Sensory neuropathy and signs of central sensitization in patients with peripheral arterial disease

Abstract Patients with peripheral arterial disease (PAD) may develop a broad range of peripheral nerve dysfunctions including pain and sensory deficiencies due to chronic ischemia mostly involving the lower limbs. To investigate the degree of sensory abnormalities in such patients quantitative sensory testing (QST) might be a useful tool. Forty‐five patients and 20 controls were enrolled in the present study and underwent QST according to the protocol of the German Research Network on Neuropathic Pain. PAD was graded according to the Rutherford classification. PAD patients were divided into two groups: 16 patients with critical limb ischemia (severe PAD) and 29 patients with intermittent claudication (moderate PAD). QST revealed impaired cold and warm detection, increased mechanical and vibration detection thresholds, and increased perceptual wind‐up on the affected leg (all p < 0.001). Paradoxical heat sensation (p < 0.05) and dynamic mechanical allodynia (p < 0.01) were also observed. Subgroup analysis of patients without diabetes (control n = 20, moderate PAD n = 21, severe PAD n = 8) confirmed most of these findings. In patients with severe PAD, sensory deficits were more pronounced than in patients with moderate PAD and were detected even in the face. These data indicate that QST can detect sensory abnormalities in PAD patients. While the pattern of decreased perception suggests deafferentation for Aβ‐, Aδ‐, and C‐fiber inputs, the presence of allodynia suggests that central sensitization also plays a role in the pain state of PAD patients. Subgroup analysis points towards a PAD‐associated peripheral neuropathy independent of diabetes.

Tetrasupersilyl-tristannaallene and -tristannacyclopropene (tBu3Si)4Sn3 – Isomers with the Shortest Sn=Sn Double Bonds to Date

The dark blue, air- and moisture-sensitive, thermolabile tristannaallene R*2Sn=Sn=SnR*2 (5) (R* = SitBu3) is prepared by reaction of Sn(OtBu)2 or Sn[N(SiMe3)2]2 with R*Na in pentane/benzene at –25°C. The dark red-brown, air-sensitive, moisture-insensitive, and thermostable cyclotri-stannene R*4Sn3 (6) with a –R*Sn=SnR*– moiety as part of a Sn3 ring is obtained from the reaction of Sn(OtBu)2 or Sn[N(SiMe3)2]2 with R*Na in pentane at 25°C or from the isomerization of 5 at room temperature (τ1/2 = 9.8 h). According to the result of X-ray structural analyses the Sn3 framework of chiral 5 is bent (156°) and the terminal Sn atoms have pyramidal surroundings. The SnSn double bonds in 5 (2.68 A) are shorter than those found for the hitherto structurally investigated distannenes (2.77–2.91 A). Even shorter is the double bond in 6 (2.59 A). The unsaturated Sn atoms here have nearly planar surroundings in perfect analogy to the carbon atoms in CC double bonds. The SnSn double bond in 6 can therefore be considered as the first “true” Sn=Sn bond. The structures of 5 and 6 can be deduced also from 119Sn- and 29Si-NMR studies in solution.

Disilene R*XSiSiXR* (R*=SitBu3) mit siliciumgebundenen H- und Hal-Atomen X: Bildung, Isomerisierung, Reaktionen

Abstract Dehalogenations of 1,2-disupersilyldisilanes R*H2SiSiHalHR*, R*HHalSiSiHalHR*, R*HHalSiSiHal2R* and R*Hal2SiSiHal2R* in THF with equimolar amounts of supersilyl sodium NaR* (R*=SitBu3=Supersilyl) lead slowly at room temperature (Hal=Cl) or fast even at −78°C (Hal=Br, I) under exchange of one halogen Hal for sodium Na to yellow–orange disilanides R*H2SiSiNaHR*, R*HHalSiSiNaHR*, R*HHalSiSiNaHalR* and R*Hal2SiSiNaHalR* (identification by protonation, methylation, silylation). These then, in the latter three cases, eliminate NaHal under formation of trans-1,2-disupersilyldisilenes R*XSiSiXR* with silicon-bound H and Hal atoms as X. Actually produced are R*HSiSiHR*, R*HSiSiBrR*, R*ClSiSiClR*, R*BrSiSiBrR* and R*ISiSiIR*. The intermediate existence of the disilenes could be proved by trapping them with diphenylacetylene (formation of [2+2] cycloadducts), with anthracene (formation of [4+2] cycloadducts), with benzophenone (formation of [2+2] cycloadducts), and/or with 2,3-dimethylbutadiene (formation of [2+2] and [4+2] cycloadducts as well as ene reaction products). Obviously, isomerization of the disilenes R*HalSiSiHalR* to silylenes R*Hal2SiSiR* is possible, the latter of which may be trapped by Et3SiH. In the absence of the mentioned traps, R*HSiSiHR* thermolizes under formation of cyclotrisilanes R*3Si3H3 and R*3Si3H2R with R=SiH2R* as well as cyclotetrasilanes R*4Si4H4, whereas R*HSiSiBrR* and R*BrSiSiBrR* react to an unidentified mixture of substances. The disilene R*ClSiSiClR* forms in the presence of its source R*Cl2SiSiNaClR* cyclotetrasilanes R*4Si4Cl4 obviously by way of insertion into the SiNa bond of the latter followed by elimination of NaCl. Finally, R*ISiSiIR* goes over into the cyclotrisilane R*3Si3I2R with R=SiI2R*, the formation of which could take place by way of [2+1] cycloaddition of the mentioned disilene and its isomer R*I2SiSiR*. In the presence of NaR*, the disilene R*HSiSiBrR* forms endo,exo- and endo,endo-bicyclotetrasilanes R*4Si4H2. Thereby, at room temperature the pure endo,endo isomer slowly transforms into an equilibrium mixture of the endo,endo and the endo,exo isomer in the mole ratio of 1:9 (the reactions of R*4Si4H2 with I2 lead to cyclotrisilanes R*3Si3HIR with R=SiHIR* and cyclotetrasilanes R*4Si4H2I2). On the other hand, the disilenes R*HalSiSiHalR* (Hal=Cl, Br, I) in the presence of NaR* quantitatively transform, possibly via the disilenides R*HalSiSiNaR* and cyclotetrasilenes R*4Si4Hal2, into the tetrahedrotetrasilane R*4Si4 (the tetrahedrane reacts with O2, I2, Na under formation of R*4Si4O2, R*4Si4I2, R*4Si4Na2). X-ray structure analyses are presented for cis,cis,trans-R*4Si4H2I2 as well as cis,trans,cis-R*4Si4Cl4 and the [2+2] cycloadducts of R*BrSiSiBrR* with Ph2CO and of R*ClSiSiClR* with CH2CMeCMeCH2.

Über das Octastannandiid R*6Sn8[Na(THF)2 ]2 und zur möglichen Existenz des Octastannans R*6Sn8 [1] / On an Octastannanediide R*6Sn8[Na(THF)2]2 and the Possible Existence of an Octastannane R*6Sn8 [1]

The black, air and moisture sensitive octastannanediide R*6Sn8[Na(THF)2]2 (4) (R* = SitBu3) is prepared by reaction of Sn[N(SiMe3)2]2 with R*Na in tBuOMe at -78°C. Red brown octastannane R*6Sn8 (5) is formed by thermolysis of the tristannacyclopropene R*4Sn3 in benzene at 100 °C. According to the result of the X-ray structural analysis, 4 contains a Sn8 cubane with six Sn atoms each connected with R* and two at the end of a space diagonal connected with Na(THF)2. A preliminary X-ray structure analysis shows 5 to adopt the same Sn8 cubane structure as 4 with two bare Sn atoms at the end of a space diagonal.

Dimere der Ethene Me2EC(SiMe3)2 (E=Si, Ge, Sn): Auf welchem Wege entstehen sie aus Me2EXCM(SiMe3)2? Wie sind sie strukturiert?

Abstract Alkali metal organyls or silyls MR (e.g. LiMe, LinBu, LitBu, LiPh, LiCH(SiMe3)2, LiC(SiMe3)3, NaSitBu3) convert equimolar amounts of bromomethanes Me2EXCBr(SiMe3)2 with E=Si, Ge, Sn and electronegative substituents X (e.g. F, Br, OPh) in organic solvents (e.g. pentane, diethyl ether, tetrahydrofuran) (i) by a very fast Br/M exchange into the ‘metalation products’ Me2EXCM(SiMe3)2, which thermolyze under formation of ‘cyclobutanes’ [Me2EC(SiMe3)2]2, and (ii) to a lesser extent by X/R exchange into ‘substitution products’ Me2ERCBr(SiMe3)2. As shown by trapping experiments, the unsaturated compounds Me2EC(SiMe3)2 play the role of short-lived intermediates in both reactions. They are formed from Me2EXCM(SiMe3)2 by MX elimination and add the present alkalimetal compounds Me2EXCM(SiMe3)2≡MR′ or MR, respectively. The products Me2ER′CM(SiMe3)2 with R′=C(EXMe2)(SiMe3)2, obtained in this way, eliminate MX under formation of the mentioned ‘cyclobutanes’. On the other hand, the compounds Me2ERCM(SiMe3)2 convert unreacted Me2EXCBr(SiMe3)2 in Me2EXCM(SiMe3)2 under formation of Me2ERCBr(SiMe3)2. Relative rates of both the metalation reactions and the salt eliminations are determined. X-ray structure analyses of [Me2EC(SiMe3)2]2 (E=Si, Ge, Sn) prove their 1,3-dielementacyclobutane structure with planar four-membered ECEC rings.

Zur Reaktivität des Silaethens Me2Si=C(SiMe3)2: Regioselektivität, Stereoselektivität und relative Geschwindigkeiten von En-Reaktionen [1] / On the Reactivity of Silaethene Me2Si=C(SiMe3)2: Regioselectivity, Stereoselectivity and Relative Rates of Ene Reactions [1]

Ene reactions of Me2Si=C(SiMe3)2 (1) with propene or with methyl derivatives of propene and 1,3-butadiene, respectively, of the formula R 1 CH=CR2-CH2R3 take place regioselectively, as well as stereoselectively and are retarded by increasing bulk of R1, R3 (for example H < CH3 < CH=CH2 < CH=CHMe), as well as accelerated by an increasing tendency of R2 to donate electrons (for example H < CH3 ≈ CH=CH2 < CH2SiMe2[CH(SiMe3)2]). It is concluded from these studies, that ene reactions of 1 occur concerted and are HOMOene-LUMOenophile controlled.

Zur Reaktivität des Germaethens Me2Ge=C(SiMe3)2: Mechanistische Aspekte der Diels-Aider- und En-Reaktionen [1] / On the Reactivity of Germaethene Me2Ge=C (SiMe3)2: Mechanistic Aspects of Diels Alder and Ene Reactions [1]

Abstract Diels-Alder and ene reactions of germaethene Me2Ge=C(SiMe3)2 (2) with butadienes respectively, take place regioselectively, as well as stereoselectively. They are accelerated by an increasing tendency of substituents in butadiene or propene to donate electrons (e.g. 2-methylbutadiene > butadiene; 2-methylpropene > propene), and retarded by an increasing bulkyness of substituents in 1,4- or 1,3-positions (e.g. 1-methylbutadiene > 2-methylbutadiene; 1-vinylpropene > propene). It is concluded from these studies that Diels-Alder and ene reactions of 2 occur - like those of Me2Si=C(SiMe3)2 (1) or of ethenes >C=C< - in a concerted way and are HOMOdiene-LUMOdienophile and HOMOene-LUMOenophile controlled. Thus 2 and 1 behave as carbon analogues. With regard to a specific diene or ene (e.g. anthracene; toluene), 2 is the better dienophile or enophile than 1 or ethenes. With a fixed diene/ene mixture (e.g. butadiene/propene), 2 acts as the better dienophile, while 1 is the better enophile. These results can be explained by the π/π*- energy difference and the double bond polarity decreasing in the direction 1 > 2. Only cis-piperylene gives a [2+2] cycloadduct with 2. besides two [4+2] cycloadducts, and an ene reaction product